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S. HRG. 107–326

MAKING SENSE OF THE MAMMOGRAPHY

CONTROVERSY: WHAT WOMEN NEED TO KNOW

JOINT HEARING

BEFORE THE

SUBCOMMITTEE ON PUBLIC HEALTH

OF THE

COMMITTEE ON HEALTH, EDUCATION,

LABOR, AND PENSIONS

UNITED STATES SENATE

AND THE

SUBCOMMITTEE ON LABOR, HEALTH, AND HUMAN

SERVICES, AND EDUCATION

OF THE

COMMITTEE ON APPROPRIATIONS

UNITED STATES SENATE

ONE HUNDRED SEVENTH CONGRESS

SECOND SESSION

ON

EXAMINING THE CONFLICTING FINDINGS REGARDING MAMMOGRAPHY

USAGE AND UPDATE RECOMMENDATION GUIDELINES, BASED ON

THE MOST CURRENT SCIENTIFIC DATA, ON THE USE OF MAMMOGRAPHY IN BREAST CANCER DETECTION

February 28, 2002

Printed for the use of the Committee on Health, Education, Labor, and Pensions

(

COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

EDWARD M. KENNEDY, Massachusetts, Chairman

CHRISTOPHER J. DODD, Connecticut

TOM HARKIN, Iowa

BARBARA A. MIKULSKI, Maryland

JAMES M. JEFFORDS (I), Vermont

JEFF BINGAMAN, New Mexico

PAUL D. WELLSTONE, Minnesota

PATTY MURRAY, Washington

JACK REED, Rhode Island

JOHN EDWARDS, North Carolina

HILLARY RODHAM CLINTON, New York

JUDD GREGG, New Hampshire

BILL FRIST, Tennessee

MICHAEL B. ENZI, Wyoming

TIM HUTCHINSON, Arkansas

JOHN W. WARNER, Virginia

CHRISTOPHER S. BOND, Missouri

PAT ROBERTS, Kansas

SUSAN M. COLLINS, Maine

JEFF SESSIONS, Alabama

MIKE DEWINE, Ohio

J. MICHAEL MYERS, Staff Director and Chief Counsel

TOWNSEND LANGE MCNITT, Minority Staff Director

SUBCOMMITTEE ON PUBLIC HEALTH

EDWARD M. KENNEDY, Chairman

TOM HARKIN, Iowa

BARBARA A. MIKULSKI, Maryland

JAMES M. JEFFORDS, Vermont

JEFF BINGAMAN, New Mexico

PAUL D. WELLSTONE, Minnesota

JACK REED, Rhode Island

JOHN EDWARDS, North Carolina

HILLARY RODHAM CLINTON, New York

BILL FRIST, Tennessee

JUDD GREGG, New Hampshire

MICHAEL B. ENZI, Wyoming

TIM HUTCHINSON, Arkansas

PAT ROBERTS, Kansas

SUSAN M. COLLINS, Maine

JEFF SESSIONS, Alabama

CHRISTOPHER S. BOND, Missouri

DAVID NEXON, Staff Director

DEAN A. ROSEN, Minority Staff Director

(II)

(III)

COMMITTEE ON APPROPRIATIONS

ROBERT C. BYRD, West Virginia, Chairman

DANIEL K. INOUYE, Hawaii

ERNEST F. HOLLINGS, South Carolina

PATRICK J. LEAHY, Vermont

TOM HARKIN, Iowa

BARBARA A. MIKULSKI, Maryland

HARRY REID, Nevada

HERB KOHL, Wisconsin

PATTY MURRAY, Washington

BYRON L. DORGAN, North Dakota

DIANNE FEINSTEIN, California

RICHARD J. DURBIN, Illinois

TIM JOHNSON, South Dakota

MARY L. LANDRIEU, Louisiana

JACK REED, Rhode Island

TED STEVENS, Alaska

THAD COCHRAN, Mississippi

ARLEN SPECTER, Pennsylvania

PETE V. DOMENICI, New Mexico

CHRISTOPHER S. BOND, Missouri

MITCH MCCONNELL, Kentucky

CONRAD BURNS, Montana

RICHARD C. SHELBY, Alabama

JUDD GREGG, New Hampshire

ROBERT F. BENNETT, Utah

BEN NIGHTHORSE CAMPBELL, Colorado

LARRY CRAIG, Idaho

KAY BAILEY HUTCHISON, Texas

MIKE DEWINE, Ohio

TERRENCE E. SAUVAIN, Staff Director

CHARLES KIEFFER, Deputy Staff Director

STEVEN J. CORTESE, Minority Staff Director

LISA SUTHERLAND, Minority Deputy Staff Director

SUBCOMMITTEE ON DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND

EDUCATION, AND RELATED AGENCIES

TOM HARKIN, Iowa, Chairman

ERNEST F. HOLLINGS, South Carolina

DANIEL K. INOUYE, Hawaii

HARRY REID, Nevada

HERB KOHL, Wisconsin

PATTY MURRAY, Washington

MARY L. LANDRIEU, Louisiana

ROBERT C. BYRD, West Virginia

ARLEN SPECTER, Pennsylvania

THAD COCHRAN, Mississippi

JUDD GREGG, New Hampshire

LARRY CRAIG, Idaho

KAY BAILEY HUTCHISON, Texas

TED STEVENS, Alaska

MIKE DEWINE, Ohio

Professional Staff

ELLEN MURRAY

JIM SOURWINE

MARK LAISCH

ADRIENNE HALLETT

ERIK FATEMI

BETTILOU TAYLOR (Minority)

MARY DIETRICH (Minority)

SUDIP SHRIKANT PARIKH (Minority)

CANDICE ROGERS (Minority)

Administrative Support

CAROLE GEAGLEY

CONTENTS

STATEMENTS

FEBRUARY 28, 2002

Page

Mikulski, Hon. Barbara A., a U.S. Senator from the State of Maryland,

opening statement ................................................................................................ 1

Specter, Hon. Arlen, a U.S. Senator from the State of Pennsylvania, opening

statement .............................................................................................................. 2

Harkin, Hon. Tom, a U.S. Senator from the State of Iowa, opening statement . 8

Reed, Hon. Jack, a U.S. Senator from the State of Rhode Island, opening

statement .............................................................................................................. 10

Von Eschenbach, Andrew, M.D., Director, National Cancer Institute, National

Institutes of Health, U.S. Department of Health and Human Services,

prepared statement .............................................................................................. 14

Berry, Donald A., M.D., Chairman, Department of Biostatistics, Anderson

Cancer Center, Unibersity of Texas, Houston, TX; and Harmon J. Eyre,

M.D., Chief, Medical Officwer and Executive Vice President ofr Research

and Medical Affairs, American Cancer Society, Washington, DC .................... 44

Prepared Statements of:

Donald A. Berry, M.D. .............................................................................. 46

Harmon J. Eyre, M.D. ............................................................................... 52

Visco, Fran, President, National Breast Cancer Coalition, Washington, DC;

Carolyn D. Runowicz, M.D., Vice Chariman, Department of Obsttretrics

and Gynecology, Saint Luke’s Roosevelt Hospital, New York, NY, On Behalf

of the American College of Obstretricians, and Gynecologists; and LaSalle

Leffall, Jr., M.D., Chairman-Elect, Susan G. Komen Breast Cancer Foundation, Dallas, TX .................................................................................................... 65

Prepared Statements of:

Fran Visco .................................................................................................. 67

Carolyn D. Runowicz, M.D. ...................................................................... 73

LaSalle D. Leffall, Jr., M.D. ..................................................................... 76

ADDITIONAL MATERIAL

Articles, publications, letters, etc.:

Danish Study .................................................................................................... 21

Claudia I. Henschke, PhD., M.D. .................................................................... 88

Letter to Senator Specter from UPMC Health System ................................. 89

Agency for Healthcare Research and Quality ................................................ 89

Food and Drug Administration, Department of Health and Human Services .................................................................................................................. 92

Letter to Senators Kennedy and Gregg from the Oncology Nursing Society ................................................................................................................... 94

Samuel B. Wallace ............................................................................................ 96

(IV)

(1)

MAKING SENSE OF THE MAMMOGRAPHY

CONTROVERSY: WHAT WOMEN NEED TO

KNOW

THURSDAY, FEBRUARY 28, 2002

U.S. SENATE,

SUBCOMMITTEE ON PUBLIC HEALTH, COMMITTEE ON HEALTH,

EDUCATION, LABOR, AND PENSIONS, AND SUBCOMMITTEE ON

LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION,

COMMITTEE ON APPROPRIATIONS,

Washington, DC.

The joint hearing convened at 2:28 p.m., in room SD–106, Dirksen Senate Office Building, Hon. Barbara Mikulski, presiding.

Present: Senators Mikulski, Harkin, Murray, Reed, Clinton,

Specter, and Frist.

OPENING STATEMENT OF SENATOR MIKULSKI

Senator MIKULSKI. [presiding]. Good afternoon.

This is a joint hearing between the Subcommittee on Public

Health of the Health, Education, Labor, and Pensions Committee

as well as the Appropriations Subcommittee on Labor, Health and

Human Services, and Education.

We are holding a joint hearing because of the advocacy of the

members and the way that both the authorizing and appropriating

committees have worked together.

The title of this hearing is ‘‘Making Sense of the Mammogram

Controversy: What Women Need to Know.’’ As chair of the hearing, I wish to yield to the ranking member

of the Appropriations Committee, Senator Arlen Specter. Senator

Specter is co-chair of the Steel Caucus, and he, along with other

Steel Caucus members, has a meeting with the President in about

20 minutes.

As a Senatorial courtesy, we would like him to go first, because

he is going to go and be representing thousands of steel workers,

and as a member of the Steel Caucus, Senator, my thoughts go

with you. I will hold the fort here at the committee, and I know

you will with the President.

I would ask my colleague to proceed, and I just want to emphasize what a bipartisan effort this is, helping women to be protected

from the ravages of breast cancer, and what a strong advocate Senator Specter has been for the empowerment of women in being able

to have the health care they need.

Senator?

2

OPENING STATEMENT OF SENATOR SPECTER

Senator SPECTER. Thank you very much, Madam Chairperson,

for your initiatives and your leadership in convening this important

hearing, and thank you for yielding to me for a few moments.

Senator Mikulski and I have just come from the Ellipse. It is

about 35 degrees outside in Washington today, and there was a

rally of some 25,000 steel workers who came to urge the President

to impose tariffs to allow the steel industry to revitalize itself. Senator Mikulski and I spoke there, and we are glad to be indoors for

a few minutes at this time.

As Senator Mikulski has said, the President has scheduled a

meeting of the Steel Caucus of which I am vice chairman, and we

will be meeting with the President shortly to make the case as to

why we ought to stop subsidized and dumped steel from coming

into the United States, costing the bankruptcies of many corporations, the loss of hundreds of thousands of jobs and impairing our

capacity for national defense.

But I wanted to be here for at least a few minutes this morning,

and I will return if I can before the hearing is concluded, on this

very important subject of mammography.

I chaired the appropriations subcommittee which funded the Department of Health and Human Services in 1997, when a controversy arose as to whether there should be mammograms for

women between the ages of 40 and 49 and, in my capacity as chairman of that subcommittee, initiated a series of hearings on the

subject and became personally convinced that the mammograms

could be helpful—not necessarily but possibly so, that if a

noninvasive screening process could detect breast cancer at an

early age and save lives, and the statistics are just devastating as

to how many women die of breast cancer each year, it ought to be

available.

The issue came before the appropriations subcommittee because

it was a matter of cost. Senators ought not decide medical questions; we ought to leave that to the experts. But when it comes to

the issue of establishing priorities on where expenditures ought to

be allocated, that is the prerogative of the Members of Congress of

the House and Senate.

We decided that we could afford it, and that is part of what Senator Harkin and I have done on many of these important medical

issues. Senator Harkin and I have taken the lead on funding for

NIH from $12 billion a year to $23 billion a year. We are a rich

and powerful country, and we can afford that. And the funding for

cancer has increased enormously, including funding for breast cancer. Of the $2.1 trillion which is spent by the United States Government each year, none is spent for a better purpose than to try

to eradicate breast cancer, prostate cancer, eliminate Alzheimer’s,

Parkinson’s, and heart disease. There is nothing more important

than health.

So I am pleased that these hearings have been convened. Let us

take a fresh look at the matter. There is some potential if someone

has a mammogram and there is a false positive, but my own personal view after studying the matter in great detail is that that is

of lesser consequence than the availability of screening to detect

3

cancer at an early stage where it can be successfully treated. And

I believe that the United States Government has the funding to

make such mammography available for women ages 40 to 49; but

reconsideration is always fine.

Since I have to leave, I want to introduce Ms. Fran Visco, who

is president of the National Breast Cancer Coalition and a member

of the board of directors. President Clinton appointed her as a

member of the President’s Cancer Panel. She has a degree from

Saint Joe’s and a law degree from Villanova Law School, and she

is a Pennsylvanian, which gives us special pride.

While I am at it, I want to note the presence of the distinguished

new head of the National Cancer Institute, Dr. von Eschenbach,

who comes from South Philadelphia. It is a high honor to be director of the National Cancer Institute, and it may be an even higher

honor to be from South Philadelphia.

Thank you very much, Senator Mikulski.

Senator MIKULSKI. Thank you, Senator, and good luck to you in

your meeting with the President. Give him my regards that it is

a bipartisan effort. We have got to be Team USA here.

Thank you.

In my own opening statement, I want to say that the title of this

hearing is ‘‘Making Sense of the Mammogram Controversy: What

Women Need to Know,’’ and what women need to do.

Today we are here to examine the very troubling controversy

about the effectiveness of screening mammography. Women are

hearing conflicting scientific studies. Some studies say that mammogram save lives. Others say they do not. This is incredibly frustrating for American women. Many are confused, exasperated, and

apprehensive, both about breast cancer and now about the information they are getting about mammography. They do not know what

to do, whom to believe, or where to go.

I am very concerned myself. I called this hearing to get answers

for American women. What should they do? Where can they get information they can rely upon?

Also, in the absence of conclusive information, I am worried that

insurance companies will wiggle out of providing this coverage, saying that it is no longer a mandate for prevention but a personal option. I do not believe that mammograms should be equated with

nose jobs. I do believe that mammograms save lives, and we need

to know when is the best time to get them.

There are conflicting studies. Recent work by biostatisticians in

Denmark concluded that there is no reliable evidence that regular

mammograms save lives. Here in the United States, the Physicians’ Data Query Screening and Prevention Board—which, by the

way, is an independent group of experts created and funded by the

National Cancer Institute—has come up with these observations.

They have signalled yellow flashing lights about whether mammograms provide any benefit to women. These findings conflict with

other studies showing that screening mammograms can reduce

breast cancer deaths by 30 percent.

Then, in the atmosphere of these conflicting studies, last week,

Secretary Tommy Thompson affirmed the Department’s traditional

position that regular mammograms do benefit women and cited the

Preventive Services Task Force. But at that time, Secretary

4

Thompson, a longstanding advocate of women’s health, did not give

us data.

Many other organizations like the American Cancer Society also

continue to recommend screening mammograms.

So today, we want to hold a hearing. This is not a debate. It is

a presentation of views in which we hope we can clear the air and

clear up what women should do. I understand dissent in the scientific community and difference of opinion about particular studies, but this conflict is exasperating. Women do not know whom to

believe or what they should do.

My own position is that I would rather be safe than sorry. But

I also have the means to pay for a mammogram. What about

women who do not have the ability to pay? What happens if insurance companies decide to stop paying? And in the absence of clarity, I am concerned that conflicting studies will give women pause

rather than pursuing prevention.

We do need new tools and techniques regardless of the efficacy

of mammograms. Right now, what we do know is that the mammogram is the best tool we now have—but it should not be the only

tool. Hopefully, there will be more in the future. We need new tools

and accurate testing to make sure they work. We cannot afford to

have the same controversy over and over again.

The Institute of Medicine has recommended improving the development and adoption of new technologies as well as maximizing

the technology currently available for breast cancer detection.

These recommendations should be seriously considered.

At the same time that we look at new technologies, we have to

make sure that mammograms, regardless of when we are advised

to get them, are safe. That is why in 1992, I led the way to ensuring that we had Mammogram Quality Safety Standards to be sure

that they are safe and accurate, to avoid, of course, the terrible situation of false negatives. These Mammogram Quality Standards

are now up for reauthorization, and we hope to be able to expedite

that and look forward to any comments that others wish to make.

This hearing brings together the Public Health Subcommittee

and the Labor-HHS Appropriations Subcommittee to look at these

issues. I am happy to say that I am joined by Senator Tom Harkin,

who chairs the Labor-HHS Appropriations Subcommittee. Senator

Harkin is a longstanding advocate for doubling the funding for the

NIH budget, to ensuring that American people have access to

health care and the cures that they help pay to discover, and at

the same time, when women were not even included in the clinical

trials, he was a real Galahad to make sure we created the Office

of Women’s Health at NIH and had the money in the Federal

checkbook so that we could pursue those issues of research in

breast and ovarian cancer.

So, Senator Harkin, we thank you for being here, and of course,

we welcome Dr. Andrew von Eschenbach.

[The prepared statement of Senator Mikulski follows:]

PREPARED STATEMENT OF SENATOR MIKULSKI

Today we are here to examine a troubling controversy about the

effectiveness of screening mammography. Women are hearing

about conflicting scientific studies. Some say mammograms save

5

lives. Others say they don’t. This is incredibly frustrating for

women. Many are already apprehensive about breast cancer. Now

they don’t know what to do or who to believe.

I am frustrated myself. I called this hearing to get some answers

for American women. What should they do? Where do they get information they can trust? We also don’t want insurance companies

to wiggle out of providing this coverage because they say the data

is inconclusive.

Recent work by statisticians Dr. Peter Gotzsche and Ole Olsen

of the Nordic Cochrane Center in Denmark concluded that there is

no reliable evidence that regular mammograms save lives. This

finding conflicts with other studies showing that mammograms reduce breast cancer deaths by about 30%. Here in the United States,

the Physicians’ Data Query Screening and Prevention Board, a

panel of independent experts created and funded by the National

Cancer Institute, has signaled its yellow flashing lights about

whether mammograms provide any benefit to women. Last week,

Secretary Tommy Thompson reaffirmed the Department’s position

that regular mammograms do benefit women. Many other organizations, like the American Cancer Society, also continue to recommend screening mammograms.

I understand dissent in the scientific community and differences

of opinion about particular studies, but this conflict is exasperating. Women don’t know who to believe or what they should do— do they get a mammogram or not? My position is that I would

rather be safe than sorry, but I have the means to pay for a mammogram. What about women who don’t have the ability to pay and

whose insurance companies may decide to stop paying for mammograms? In the absence of clarity, I’m concerned that these conflicting studies give an excuse to insurance companies to stop paying

for mammograms.

I’m not mandating an outcome, but this is very troubling. I speak

for the women of the Senate and I salute the wonderful men who

are so supportive and real champions like Senators Harkin, Specter, and Frist.

Mammography is the best tool we have now, but it is not the

only one and there will be more in the future. We need new tools

and accurate testing to make sure they work. We cannot afford to

have this same controversy over and over. A report last year by the

Institute of Medicine recommended improving the development and

adoption of new technologies, as well as maximizing the technologies currently available for breast cancer detection. These recommendations should be seriously considered.

Mammography is not perfect, but it is the best screening tool we

have now. Mammograms must be as safe and accurate as possible.

A mammogram is worse than useless if it produces a poor-quality

image or is misinterpreted. That’s why I have fought over the last

ten years to make them even better. The Mammography Quality

Standards Act (MQSA) that I authored has improved the quality

of mammograms in this country over the last ten years. MQSA has

brought facilities nationwide into compliance with federal quality

standards. Before MQSA, tests were misread, women were

misdiagnosed, and people died as a result of sloppy work. This year

Congress must reauthorize the Mammography Quality Standards

6

Act, because women must continue to have safe, quality mammograms. Until there are more effective screening tools, mammography is still the front line against breast cancer.

This hearing brings together the Public Health Subcommittee

and the Labor/HHS Appropriations Subcommittee to look at this

issue of great importance to women. I look forward to the testimony of our witnesses and the expertise they bring. I extend a

warm welcome to Dr. Andrew von Eschenbach, the new Director of

the National Cancer Institute, as he testifies at his first hearing.

I also enter into the record statements from the Food and Drug Administration and the Agency for Healthcare Research and Quality

that are valuable contributions to this hearing. Whether or not to

get a mammogram is a decision faced by millions of women. They

are looking for answers and recommendations based on sound

science, and they deserve no less.

Senator MIKULSKI. Before I turn to Senator Harkin, I would like

to note that Senator Olympia Snowe, a dear colleague, will not be

able to attend today. For more than 20 years in the House and the

Senate, we have been paired up as advocates in terms of helping

not only to race for the cure but to race for every other tool we had

to be able to find a cure and for prevention.

Senator Snowe has sent a statement for the record, and I ask

unanimous consent that it be included in the record.

[The prepared statement of Senator Snowe follows:]

PREPARED STATEMENT OF SENATOR SNOWE

Chairwoman Mikulski, Chairman Harkin, thank you for inviting

me to join you and your committees today for this very important

hearing, as we try to make sense of the controversy surrounding

the merits of mammograms. Having worked with both of you over

many years on this issue, I am pleased to have this opportunity to

continue our joint efforts to improve women’s health.

The uncertainty around the merits of mammography has gone on

for almost 25 years, beginning in 1977 when the National Cancer

Institute stopped recommending mammograms for women in their

40s. Since then, there have been three additional reversals of the

policy on mammography for this class of women . . .

And what has all of this back and forth accomplished? Well it’s

done only one thing well, and that’s create confusion and uncertainty on a matter that’s central to a woman’s health. As this debate wears on, women are becoming more and more uncertain of

what science and what good health practices dictate they should do

to be a partner in the fight against cancer, using the best weapon

we all know of . . . early detection. Putting aside for a moment the

controversy surrounding mammograms, no one can argue that

early detection is not a critical component in the fight against

breast cancer. Finding breast cancer earlier through mammography

and earlier treatment has led to a steady decline in death rates.

Not coincidently, as the number of women who received mammograms doubled, the average size of a tumor when it is originally detected has shrunk from three centimeters to two. And both common

sense and experience tells us that detecting the tumor earlier,

when it’s smaller, improves the ability to treat the cancer before it

spreads.

7

Women have certainly taken the importance of routine mammograms and early detection to heart, playing an active role in their

health maintenance by getting their annual or bi-annual screening.

In fact, according to the 2000 Behavioral Risk Factor Surveillance

System, the percentage of U.S. women aged 40 and older who had

a recent mammogram was almost 63 percent.

And why are women consistently going for these screenings?

Consider the everyday experience of women, knowing not only the

grim statistics that one in eight women will develop breast cancer

in their lifetime, but also—all too often—having personal experience in confronting the devastation of breast cancer, when facing

the diagnosis of a grandmother, mother, sister, or friend. I know

the impact my mother’s diagnosis had on me, as an eight-year old,

and the impact her death from the disease had on inspiring me to

make combating breast cancer a top priority.

And yet, the debate about the efficacy of mammograms has

thrown a shadow over the one tool available to women to protect

themselves. The latest round in this debate began last fall, when

the British medical journal, The Lancet published a Danish study

which re-examined and confirmed the authors’ original opinion that ‘‘there is no reliable scientific evidence that screening for breast

cancer reduced mortality.’’ Having been active in this debate

throughout my tenure in Congress and as the author, with Senator

Mikulski, of the 1997 resolution adopted unanimously by the Senate highlighting the need for accurate guidelines for mammography

for women in their 40s, I am concerned, but not surprised, that this

controversy has arisen again.

My concern led me, along with Senator Mikulski, to write to the

Acting Director of the National Cancer Institute requesting that

NCI, among other things, clarify the conflicting findings and recommend updated guidelines for the use of mammography in breast

cancer detection. We have also been in contact with the newly-appointed Director, Dr. von Eschenbach, who is appearing today. Dr.

von Eschenbach has been very receptive to our concerns and has

indicated his intent to be active on this issue.

We did not need to wait too long for this action, as last week,

NO endorsed the recommendation of Health and Human Services

Secretary Thompson, affirming the current recommendation that

women in their forties get a mammogram once every year or two.

These strong endorsements of routine mammograms were a definitive signal as to the position of the public health infrastructure.

While their statements are encouraging, as long as the controversy

remains in the national press, it will continue to weigh heavily on

women and their families, on a matter that is too often of life and

death.

It is my sincere hope that this hearing will be the beginning of

the end of the almost twenty-five year controversy surrounding the

value of mammography. Certainly, we all recognize that there is no

‘‘silver bullet’’ in the fight against breast cancer—or any cancer for

that matter. But, in order to fight this fight the best we can, it’s

critical that we use all the tools in our arsenal. Today, early detection of cancer through mammograms represents a powerful weapon

in the war against cancer and I hope and trust that through investments in research we will continue to develop new and better

8

weapons to fight cancer. But until that day comes, I urge the witnesses here today to continue their efforts to make this a reality.

Thank you.

Senator MIKULSKI. Senator Harkin, I will now turn to you.

OPENING STATEMENT OF SENATOR HARKIN

Senator HARKIN. Senator Mikulski, thank you very much, first

for your dynamic and great leadership on so many issues that affect the health and welfare of the people of our country, but especially on this issue. You are more than generous in your remarks

about my work in this area, but I can assure you that I am just

following your lead.

Senator Mikulski correctly stated that in 1992 she authored the

legislation that provided for standardization and quality in terms

of mammograms and the interpretation of mammograms. So I

know that what is transpiring right now is of the utmost importance to her, as it is to all of us. But she really took the lead on

this, and I just want to thank her for her foresight 10 years ago

in addressing this issue.

I also want to thank you, Senator Mikulski, for your work on our

committee to make sure that we get the funds needed for intervention and especially for research. We made a commitment 5 years

ago as a Congress, the Senate and the House, that we were going

to double funding for NIH over 5 years and with the budget this

year we will accomplish that goal. Of course, a great deal of that

goes into research on cancer and also into breast cancer research.

I think that what we have to keep in mind is that we have an

epidemic in this country of breast cancer. This is an epidemic by

any yardstick or measurement. One out of every nine women in

America will get breast cancer in their lifetime. Every 3 minutes,

a woman is diagnosed with breast cancer in this country. Every 13

minutes, a woman dies of breast cancer in this country. That is an

epidemic.

I know these are statistics and we frequently throw out figures

and statistics. But these statistics involve real people. One reason

I have been so involved in this is—and I am frank to admit it— personal. My only two sisters died of breast cancer at quite an

early age. They had young families. Had they had early intervention and early screening, I daresay they would have lived a lot

longer and would be alive today.

Now I have nieces, my sister’s daughters, who, because both of

their mothers died of breast cancer, I some time ago advised—I

should not say I advised them because I am not a doctor—but I

counseled them about getting early mammogram screenings because of perhaps some genetic susceptibility or something like that.

So they started to have mammograms at an early age. One of them

called me the other day and said, ‘‘Uncle Tom, what am I supposed

to do now?’’ I said, ‘‘I don’t know, but we will get the answers.’’ Just yesterday I had a conference call with a number of doctors

and nurses and breast cancer survivors in my State of Iowa. I

think the consensus was clear, Senator Mikulski, as you stated in

your statement, that there is no confusion and no dissension among

any of them. They believe mammograms are a very useful tool.

They are not the cure-all; they are not the only thing to do. But

9

combined with self-examination and annual physicals, mammograms can be the key to early detection. And we all know that

early detection and early intervention means a woman can live

longer and have a better quality of life.

So I hope we can clear up some of this. I am sorry I came in a

little late, Madam Chair. I just heard you say that we are not here

to debate or anything like that. I understand that, but I think we

are here to shed some light on these studies. We are here to find

out from the experts and from breast cancer survivors, people who

have been involved in this for a long time—I see Fran Visco out

there—who can give us some guidance and direction and who can

reassure the women of this country of what they should do to protect their health and make sure they get early screening and early

intervention.

So Madam Chair, let me again thank you for taking the lead in

this. Thank you for pulling our two committees together to look at

this and to have what I think is a very, very vital hearing at this

point in time.

Thank you, Madam Chair.

[The prepared statement of Senator Harkin follows:]

PREPARED STATEMENT OF SENATOR HARKIN

Thank you, Senator Mikulski and thank you for joining me in

chairing this joint hearing on the benefits of mammography. I am

pleased that we have such a distinguished panel of witnesses with

us this afternoon. I particularly want to welcome the new director

of NCI, Dr. Andrew von Eschenbach, who is making his first appearance before our subcommittee.

Breast cancer is a disease I take very seriously. I lost my only

two sisters to this killer. Sadly, they contracted the disease at a

time when regular mammograms and improved treatment methods

were not widely used or available. I’m convinced to this day had

they gotten regular screenings, they would have lived longer lives.

We have a breast cancer epidemic in this country. Every three

minutes, a woman is diagnosed with breast cancer, and every 13

minutes, a woman dies from the disease. We need to wage a war

against this epidemic. And as with any war, you want all the tools

in your arsenal to maximize your chance of victory. And so while

there have been conflicting studies, I believe we need to keep

screening mammography in our arsenal. In fact, for women age 50

to 69, there is strong evidence that screening with mammograms

on a regular basis reduces breast cancer deaths by 25 percent to

30 percent.

I have read quite a bit about the new study by a pair of Danish

researchers. I have also heard that this has led to a lot of confusion

by woman facing the decision of whether to be screened regularly.

Yesterday, I talked by phone to a number of clinicians and breast

cancer survivors in Iowa. There was no confusion with them. These

Iowans, who work with patients every day feel very strongly about

the benefits of mammography and the early detection that it provides. Every one of them had a personal story about an Iowan,

whose cancer was detected early by a mammogram, and is now

doing very well. They all agreed that access to mammography is

critical. Especially for Medicare beneficiaries.

10

So I believe we need to redouble our efforts to maintain women’s

access to screening. That means improving Medicare’s unacceptably

low reimbursement rates and continuing to expand the breast and

cervical cancer screening program.

But, let me be clear, mammography is not a cure all. We need

to continue our efforts to improve treatments and eventually develop a vaccine or cure for breast cancer. That is the ultimate victory. And the key is research. A decade ago, the Federal Government spent barely $90 million on breast cancer research. Today, I

am proud to say, we’ve increased that investment to about $800

million. That investment is leading to new discoveries about the

causes of breast cancer and its prevention, detection, diagnosis,

treatment and control.

Given the stakes, I’m very interested to hear from the experts we

have here today. With that, I’ll turn to my colleague, Senator Specter, for his opening statement.

Senator MIKULSKI. Thank you, Senator Harkin.

Senator Reed?

OPENING STATEMENT OF SENATOR REED

Senator REED. Thank you very much, Madam Chairman.

I simply want to commend you for taking the initiative along

with Senator Harkin on this very important issue and simply add

to your praise of both Senator Harkin and Senator Specter for their

role over many years in trying to ensure that we have the resources to provide support in this very important area.

But ultimately, your leadership, Madam Chairwoman, has been

the critical factor, I think, in this whole debate. I am here to learn

and to listen, and with that, I will yield back my time.

Senator MIKULSKI. Thank you.

At this time I submit for the record statements from Senator Jeffords and Senator Hutchison.

[The prepared statement of Senators Jeffords and Hutchison follow:]

PREPARED STATEMENT OF SENATOR JEFFORDS

Madam Chairwoman, I want to commend you for holding this

timely hearing on the quality of mammography screening. I also

would like to extend a warm welcome to the panel of expert witnesses here today. I look forward to your testimonies so that we

may all gain a better understanding of the current controversy surrounding mammography. It is my hope that this and other sessions

like it will lead us all to better, more informed solutions in the

fight against cancer. We have made remarkable progress in the

areas of research, diagnosis and treatment over the 30 years since

we first declared the ‘‘war on cancer’’, but much more remains to

be done. In my own home state of Vermont, the American Cancer

Society estimates nearly 3,000 new cancer cases, including hundreds of new breast cancer cases in the year 2002 alone.

Recent studies have raised questions and left doubts for millions

of women and their loved ones about the efficacy of mammography

screening. Given these new uncertainties, I think it is all the more

important that the public gets the best information and analysis

11

available. We must continue to make accurate information available, and we need to avoid confusing the women for whom this

issue is so vitally important. I hope, as we all do, that we will soon

arrive at answers to the many questions before us on this matter.

In the end, the most important conclusion to reach will be one that

offers more effective screening and treatment options for women.

This week I was pleased to join Senator Dianne Feinstein, yourself Chairwoman Mikulski and many of our other colleagues in cosponsoring The National Cancer Act of 2002. It is a modernization

and enhancement of the original National Cancer Act of 1971,

which was a result of President Richard Nixon’s ‘‘war on cancer.’’

This legislation would increase funding for the National Cancer Institute (NCI), provide incentives and increased compensation for researchers and physicians, and improve and expand the recruitment

and training of health care workers who serve in underprivileged

areas and areas with high rates of cancer. A major provision of the

bill would allow the NCI to fully fund 40 percent of the research

grant applications received, which is considerably higher than the

current level of 28%.

In a time when cancer is claiming the lives of over 500,000

Americans per year, and 1 in 8 women will develop breast cancer

in the course of their lives, it is clear to me that we must continue

to increase our investments in life-saving cancer research. Thank

you for organizing these important hearings today, and I am looking forward to learning more from our witnesses. I know it will

help us as we move to reauthorize the Mammography Quality

Standards Act.

PREPARED STATEMENT OF SENATOR HUTCHISON

Thank you, Mr. Chairman. I am glad we have the opportunity

today to disseminate the correct information in regards to mammography. It is important for women to know that mammography

is an important tool in our fight against breast cancer.

I am a cosponsor on Sen. Feinstein’s cancer legislation which was

introduced yesterday. This legislation addresses the issue of mammography. It mandates that everyone has a right to receive a mammogram who is 40 years of age or older or is at high risk of developing breast cancer. We understand the importance of mammography enough to put it into legislation. It is our responsibility to

further ensure that the public is encouraged to take the steps necessary to detect cancer at an early stage.

I am concerned after reading the recent Washington Post (February 17th) article that women will not be encouraged to get a

mammogram. The head of general medicine at a Seattle hospital

stated that she was not pressuring women to have a mammogram.

If there are questions or misinformation at that level of expertise,

then what is the general public thinking? Women don’t necessarily

want to have one in the first place and if an ‘‘out’’ is presented to

them, then they may take it.

This is why I reiterate that it is important that we get the correct information out about mammography and that screening

should start at 40. More than 2,600 women in Texas will be diagnosed with breast cancer this year and it would be greatly disturbVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00015 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
12

ing to have these numbers rise higher when we are just beginning

to win the battle.

I hope at this hearing today we clarify the issues for ourselves

and the public.

Senator MIKULSKI. We are now going to turn to our first witness,

Dr. Andrew von Eschenbach, who is director of the National Cancer Institute at the National Institutes of Health. He is the 12th

director of the NCI and comes as an academician, a scholar, a researcher, and a clinician. His area of expertise has been prostate

cancer, but he has also been a consulting professor in the department of cancer biology at M.D. Anderson Cancer Center and has

led a faculty of more than 1,000 cancer researchers and clinicians,

as well as serving in the Navy. There are many things that can be

said about his articles and his very hard work.

We really welcome you, Dr. von Eschenbach. We are going to

count on you for your expertise and your leadership on this topic.

We will now turn to you. Thank you.

STATEMENT OF DR. ANDREW VON ESCHENBACH, DIRECTOR,

NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF

HEALTH, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Dr. VON ESCHENBACH. Thank you, Senator, and good afternoon,

distinguished members of the subcommittees.

I am very pleased to present my first official testimony as director of the National Cancer Institute and to do so on the important

public health issue of mammography and to provide guidance on

both the scientific and clinical dimensions of this problem, and to

also make clear why the National Cancer Institute remains committed to its use of mammography as one tool in our fight against

breast cancer.

I ask that my full written statement be included in the hearing

record.

Senator MIKULSKI. Without objection.

Dr. VON ESCHENBACH. I am joined today by Dr. Peter Greenwald,

director of the National Cancer Institute’s Division of Cancer Prevention, and by Dr. Barbara Reimer, director of our Division of

Cancer Control and Population Sciences. These two individuals

have worked tirelessly on this issue and have contributed so much

to our understanding of early detection strategies.

Along with the millions of women threatened by breast cancer,

we at the National Cancer Institute are grateful to you, not only

for your addressing this issue today but for all the effort you have

expended in the past to help make more effective early detection

and treatment options available to women.

As you know all too well, cancer is a complex disease, and our

solutions to this menace are likewise complex but also deliberate.

As scientists and clinicians, we examine, we evaluate, we learn,

and we intervene, and through it all, we continue to drive forward

toward our goal to save lives and to eliminate suffering.

This has been the story with our continuing struggle against

breast cancer. Many years ago, we embarked on this journey to

save the lives of women with breast cancer by detecting the disease

early, when we could apply more effective therapies. Our tool iniVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00016 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
13

tially for early detection was breast examination to detect a lump;

then, in the 1960’s, x-ray detection using mammography began to

be employed, especially in North America and Europe.

From the 1960’s to the 1980’s, seven randomized clinical trials

that enrolled over 400,000 women were conducted to determine

whether mammography, when used as a screening tool in women

with no symptoms or sign of breast cancer, would then result in decreased mortality from breast cancer.

These data have been subsequently analyzed, examined, and reexamined by organizations like the National Cancer Institute, the

American Cancer Society, the American College of Radiology, the

U.S. Preventive Services Task Force, and many others. These reviews ultimately led the National Cancer Institute and the American Cancer Society to together issue a recommendation in 1997

that mammography was beneficial to women in saving their lives

from breast cancer, beginning with examination starting at age 40.

As you have mentioned, Senator, a recent critique of these major

clinical trials has reawakened the debate by casting doubt on the

absolute value of mammography. While my written testimony provides more specific details, the bottom line is that the National

Cancer Institute has reviewed this latest analysis and, after careful

and serious deliberation, we have concluded that the weight of evidence continues to show that mammography saves lives through

early detection, which permits treatment of the disease at an earlier stage.

This conclusion is shared by the U.S. Preventive Services Task

Force, an independent panel of private sector experts in prevention

and primary care that is sponsored by the Agency for Health Care

Research and Quality.

Senators, allow me to be clear in my testimony. As the director

of the National Cancer Institute, who is also an investigator, a clinician, and a cancer patient, I want to assure you and the women

of this Nation that we are being vigilant regarding evaluation of all

information on early detection of breast cancer; that we are dedicated to continuously improving the diagnosis and treatment of this

disease to save lives; and finally, to reaffirm the following recommendation that, beginning in their forties, women should be

screened for breast cancer with mammography every one to 2

years.

In my written testimony, I have provided you with detailed information regarding our vigilant examination and monitoring of the

data, our insights into the debate among the experts, and I have

enumerated many of the programs that are being sponsored by the

National Cancer Institute to improve early detection and treatment

of breast cancer.

Today in my oral testimony, I would like to focus on what I believe is the crux of the issue. In this first chart, the women of this

Nation need to know that while we are far from declaring victory,

we are headed in the right direction. In the past 10 years, overall

mortality rates from breast cancer continue to fall. We first saw

this encouraging trend in 1989, with the decreasing death rate of

1.4 percent per year. More recently, the decrease has sharpened to

3.2 percent per year.

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There are significant declines for all ages, and this reduction in

death rates has resulted over time in 38,000 saved lives. We have

a long way to go, particularly to address the gap between white

and black women. But we must ensure that as we go forward, this

downward trend that we see here continues.

There are multiple factors that can be attributed to this decline.

We also need to understand that it is a complex interaction of both

the value of early detection, namely, the application of mammography, and the application of better therapies that are being developed and applied to women who are diagnosed with breast cancer.

This is an equation in which both factors leading to that decline

are important. Experts may argue about the degree to which one

of those factors may or may not be contributing to the outcome, but

clearly, both factors are of importance, and both factors must remain in the equation, because without detection, treatment is not

possible.

At the same time, we must remember that we have to continue

to focus on further downturn in that curve, and in that regard, we

must continue to monitor information to determine better methods

of early detection; we must at the same time contribute to more improved methods of therapy so that together, they will result in the

most appropriate outcome that you have asked for, namely, that we

save lives of women with breast cancer.

I would like to once again reassure the women of this Nation

that the National Cancer Institute stands today by its recommendation of mammography screening beginning in women in

their forties, and that we are doing everything we can so that tomorrow, we can improve prevention, screening, treatment, and supportive care so that we will continue these encouraging trends in

survival that we have seen over the last decade.

I thank you for the opportunity to testify about this vitally important topic, and I will be pleased later to respond to your questions.

[The prepared statement of Dr. von Eschenbach follows:]

PREPARED STATEMENT OF ANDREW VON ESCHENBACH, M.D.

Good afternoon, members of the Subcommittees. I am Andrew von Eschenbach,

M.D., Director of the National Cancer Institute (NCI). I am pleased to present my

first official testimony as the new Director of NCI before these distinguished Committees on the very important public health topic of mammography.

I would like to begin with a very concise summary of the position of NCI and the

Department of Health and Human Services (HHS) on mammography and our current plans. I will expand on these later in my testimony. Let me assure you that

NCI is collaborating with other agencies within the Department, including the

Agency for Healthcare Research and Quality (AHRQ) and the Centers for Disease

Control and Prevention (CDC), to ensure that together we are providing the latest

science, clinical recommendations, and programs to prevent, screen, diagnose, and

treat breast cancer.

Breast cancer mortality continues to fall, and that is very good news. Death rates

from breast cancer first began to decline in 1989 at 1.4 percent per year. More recently the decrease has improved to 3.2 percent per year. This is a significant decline for all ages. Unfortunately, the decline began later (1993) and is lower for

Black women, whose breast cancer death rates are 33 percent higher than rates for

all women.

We feel confident that mammography has contributed to this decline, but mammography alone has not driven this trend. Advances in therapy, including adjuvant

therapy (both hormonal and chemotherapy) and chemoprevention approaches (such

as tamoxifen) have also played a role. Unfortunately, the current debate appears to

be focused on this single component in the equation. What we need to keep in mind

15

is that many factors taken together are responsible, all are important, and we cannot eliminate any from our current approach to breast cancer. Women need

unimpeded access to prevention, screening, treatment, and supportive care to win

their battle against breast cancer, and we need to keep our focus on the sum of the

equation: longer life coupled with better quality of life.

NCI continues to recommend mammography screening for women beginning in

their forties. This is consistent with the recently released report of the U.S. Preventive Services Task Force (USPSTF), an independent panel of private-sector experts

in prevention and primary care sponsored by AHRQ. On February 21, 2002, HHS

Secretary Tommy Thompson released an updated recommendation from the

USPSTF that recommended screening mammography every 1–2 years for women

ages 40 and over. As Secretary Thompson stated, ‘‘I believe that this recommendation reaffirms the importance of mammography and should substantially allay concerns about its value in safeguarding the health of women.’’ Everyone agrees that mammography detects early tumors when they are smaller,

detects more tumors, and gives a woman more options for treatment. These benefits

are substantial by themselves. The controversial issue is whether it saves lives in

the long run. We have reviewed the evidence and the USPSTF recommendation, and

we conclude that the weight of the evidence shows that mammography saves lives

through early detection and treatment at an earlier stage. We will continue to monitor and consider any new information about mammography. However, mammography as a screening technology is only one tool, and we are pursuing a strong research agenda to develop other methods, such as improved imaging techniques, to

design better ways to screen for breast cancer in the future. We will continue to

work closely with other Institutes and Centers of the National Institutes of Health

(NIH), organizations, and breast cancer patient advocates to ensure that research

findings are translated quickly into effective interventions.

How do we know what we know about mammography? The use of x-ray imaging

for the detection of breast cancer came into use in the 1960s, following technological

advances that resulted in better images that were easier to reproduce and interpret.

Initially used to assist in diagnosis, mammography was also studied for its potential

use as a screening tool. Several randomized clinical trials of mammography have

been conducted since 1963, and as these studies have been completed and the data

analyzed, the findings have added to the total body of evidence we have today. At

various times in the past decades, different organizations such as the American College of Radiology, the American Cancer Society, NCI, and others have reviewed the

available data on screening mammography, have drawn conclusions about the

strength of that evidence, and have made recommendations or statements about its

appropriate role and use. Specifically, in 1993 NCI convened a workshop of experts

to examine the available literature and data on screening mammography and to

issue a statement of the strength of that evidence. At that time, the NCI concluded

that the evidence supported mammography for women over age 50 but not under

age 50.

In the intervening years, more data were obtained on the women who participated

in the trials, and there were now enough women who had entered the trials in their

40s to more accurately assess the impact of mammography for women in their 40s.

In 1997, there was a National Institutes of Health consensus conference where an

extensive review was reported of all of the available information on screening mammography. Following that meeting and subsequent deliberations by our respective

boards of advisors, both NCI and the American Cancer Society (ACS) released modified breast cancer screening recommendations. As of 1997, both NCI and ACS recommend mammography for women starting at age 40, although on somewhat different screening intervals. Both organizations also emphasized the importance of informed decision making about mammography.

The critique by Olsen and Gotzsche that was published in The Lancet last fall

reviewed the seven randomized clinical trials of mammography that were done in

the 1960s through 1980s. They considered technical details of the trials, such as

how women were randomized into mammography and control groups, and whether

breast cancer as a cause of death was determined accurately. The authors found

technical problems in five of the clinical trials, all of which had shown a reduction

in mortality associated with mammography; they therefore called into question the

value of mammography.

The NCI has reviewed very carefully the Olsen and Gotzsche critique, and we

have concluded that their review does not warrant a departure from our current recommendation on mammography. Over 400,000 women took part in the seven randomized clinical trials that were reviewed by Olsen and Gotzsche. They examined

each of these trials and identified potential flaws that could have influenced the

findings in several of the studies. They gave little weight to the reported benefits

16

from five of the seven trials and went on to conclude that the totality of evidence

did not support screening mammography. However, difference of opinion among experts regarding design of these studies does not in itself prove that the conclusions

are wrong. After careful deliberation of the arguments, the NCI has concluded that

the value of mammography has not been refuted.

Let me give you two examples of what Olsen and Gotzsche said and why we disagree. The first clinical trial of mammography was begun in New York City in the

1960s. It was state-of-the-art at that time. Olsen and Gotzsche pointed out that

after the participants were randomized into two groups, one group to be screened

and the other not to be screened, a larger number of women were excluded from

the group to be screened than from the unscreened group. This suggested the possibility that women diagnosed with breast cancer before the study began could be included in the screened group, but not in the unscreened group, resulting in a bias

that would make it appear that mammography was useful, when this might only

have been an artifact of study design. A scientific clinical trials expert who worked

on this trial corroborated that during the nineteen-year follow-up period, any

woman with breast cancer diagnosed prior to the onset of the study was excluded

from both groups. This would correct for the potential bias suggested by Olsen and

Gotzsche.

A second claim by Olsen and Gotzsche was that in several studies, the cause of

death in the mammography screened group was more often called ‘‘died with breast

cancer,’’ while in the comparison group, women were classified as ‘‘died of breast

cancer.’’ They claimed that this could also be a bias in favor of mammography. However, this is also what you would see if mammography were in fact saving lives.

Therefore, the NCI concluded that Olsen and Gotzsche have not refuted the evidence that mammography saves lives.

The authors also failed to consider that since the time these trials were conducted, there have been improvements in mammography and the technique of biopsy as well as in treatment. We have learned much about breast cancer biology

since this time—we now think that if tumors are detected when small in size, they

have not yet developed many blood vessels, and are less likely to be aggressive or

to metastasize. Mammography can detect these small tumors and also can detect

the earliest form of breast cancer, called ductal carcinoma in situ, and surgery can

remove these lesions.

Olsen and Gotzsche’s analysis is not the first one to scrutinize the underlying

data in these studies. Other expert groups have conducted intensive reviews of the

studies and have reaffirmed previous findings of a mortality reduction benefit, most

notably the recent report of the USPSTF.

Large workshops and consensus conferences have been convened in an attempt

to reach agreement on what the data actually say, and we have all witnessed the

difficulty and frustration that ensue from these efforts to both reach agreement on

the meaning of the data and also to craft a statement that accurately reflects the

meaning. Simply put, this is not an easy task, and the conclusions reached by Olsen

and Gotzsche are at variance with other reviews by expert groups.

The National Cancer Institute has compiled a very comprehensive database about

cancer called Physician Data Query (PDQ), that contains the latest available information about cancer prevention, screening, diagnosis, treatment, genetics, supportive care, and clinical trials. Independent PDQ advisory boards have been retained

by NCI to carry out periodic evaluations of the body of scientific data and its usefulness for drawing conclusions about the state of cancer care.

At its last meeting, the PDQ screening and prevention editorial board discussed

The Lancet review and felt that Olsen and Gotzsche made some valid points about

the quality of the trials. However, no modifications to the current PDQ statement

of evidence on breast cancer screening have been made at this time; we expect that

specific recommendations will be discussed at the next meeting of the editorial

board in March 2002.

WHAT IS NCI DOING?

The NCI is committed to improving health outcomes for women with breast cancer. As part of the commitment, we will continue to strive to monitor new information as it emerges and to communicate what we learn. NCI has taken a number

of steps to improve our effectiveness in these areas. First, I have asked two of NCI’s

division directors, Dr. Peter Greenwald, Director of the Division of Cancer Prevention, and Dr. Barbara Rimer, Director of the Division of Cancer Control and Population Sciences, to lead the new NCI Breast Screening Working Group. This group

has three major tasks: one, to monitor and evaluate new information on mammography and how best to communicate the message; two, to monitor NCI’s research

17

program on imaging and molecular technologies for early detection; and three, to assess basic biology as it pertains to early detection (for example, molecular methods

to differentiate indolent from aggressive tumors).

Second, NCI has requested that the Institute of Medicine (IOM) review the evidence related to mammography and advise us on their interpretation of the evidence. This complements an ongoing initiative of the IOM to periodically update

their year 2000 report entitled, Mammography and Beyond. This report examines

the current state of the art in early breast cancer detection, identifies promising

new technologies, and how best to move the field of breast cancer screening forward.

Third, the NCI Breast Cancer Surveillance Consortium (BCSC), a cooperative

agreement between the NCI and investigators at medical research centers across

the country, is evaluating the performance of screening mammography in community practice in the United States. This research collaboration links data from mammography registries with data on cancer outcomes from pathology laboratories or

cancer registries. The Consortium consists of eight research sites located in seven

states, plus a Statistical Coordinating Center. As of April 2001, the Consortium’s

database contains information on 2.2 million screening mammographic examinations and 28,000 breast cancer cases. This is a tremendous resource that can tell

us much more about how mammography is performed in community practice.

The Breast Cancer Surveillance Consortium supports a wide-ranging portfolio of

research projects that use population-based databases to evaluate the performance

of screening mammography in community practice. Researchers at individual sites

conduct analyses using data collected at their sites. In addition, all sites transmit

their data to a centralized Statistical Coordinating Center located at the Group

Health Cooperative site. This allows Consortium researchers to conduct analyses

across sites using pooled data.

Research in the Consortium examines issues such as the effect of breast density

and hormone replacement therapy on the accuracy of screening mammography, the

relationship of mammography assessment with final recommendations for diagnostic

evaluation, biologic characteristics of breast cancers detected by mammography

screening, and rates of detection of ductal carcinoma in situ among screened women.

Anticipating the need to track the diffusion of new screening technologies in clinical

practice, the Consortium is developing measures for tracking the use of digital mammography, which is a promising emerging technology, and will serve as a model for

tracking the diffusion of other new technologies as they emerge.

POPULATION DATA SUPPORT A BENEFIT FOR MAMMOGRAPHY

In addition to data from clinical trials, we also have data from our populationbased Surveillance, Epidemiology and End Results (SEER) registries that can be

used to track new cases and deaths from breast cancer and to examine these in relation to changes in mammography use over time. NCI also has created a national

collaboration of some of the Nation’s leading statisticians, called Cancer Intervention and Surveillance modeling NETwork (CISNET), to examine important questions about trends in breast cancer and other diseases by using the latest modeling

methods. Although preliminary, recent work by the statisticians leads to the following conclusion: breast cancer incidence rates by stage showed a decline of later stage

disease and larger size tumors and an increase in smaller, early stage tumors and

pre-invasive cancers. Modeling this shifting of cases to earlier tumors with better

prognosis predicted a decline in mortality during recent years, accounting for about

one-quarter to one-third of the observed decline in breast cancer mortality since

1990. The important fact is that back in the late 1980s, our statisticians predicted

that if mammography rose over the next decade, there would be a subsequent decrease in mortality. We are now seeing that decrease.

BEYOND MAMMOGRAPHY

There is no doubt that thousands of women are alive today because their breast

cancers were treated successfully after having been detected by mammography.

There also is no doubt that we have plenty of opportunity for improvement. We need

better ways to detect breast cancer in its very earliest stages and to prevent its further growth. While mammography is the best technology we have available today,

it has limitations. Tumors that exist, especially in dense breast tissue of younger

women or located close to the chest wall, may be missed (false negative), while in

other women there may be indications that cancer is present when it is not actually

present (false positive), leading to a series of additional procedures such as repeat

mammograms and/or biopsies. The debate about the role of mammography will continue until we have a better technology that more accurately predicts a woman’s

18

risk of developing breast cancer, and NCI is supporting a broad range of research

on promising new approaches to breast cancer screening and early detection.

Imaging research supported by NCI is advancing on several fronts. Along with efforts to improve conventional and digital x-ray mammography, NCI also supports

research for several other technologies such as magnetic resonance imaging (MRI),

ultrasonography, positron emission tomography (PET), and single photon emission

computed tomography (SPECT). Already, with these technologies, scientists can

‘‘see’’ and monitor biological processes taking place in living tissues such as blood

flow, oxygen consumption, and glucose metabolism.

A major research effort is under way to capitalize on the abundant discoveries in

cancer biology and create imaging technologies that can noninvasively detect and

display the actual molecular events taking place in the body. Molecular imaging will

allow researchers to detect altered gene products and tumor-specific receptors or enzymes. The ability to visualize molecular pathways involved in the development of

tumors is expected to enable researchers to detect and stage tumors more easily,

to select more effective treatments, and to predict the effectiveness of new drugs.

Some specific examples of research supported by NCI:

Digital Mammography.—In 2001, the American College of Radiology Imaging Network (ACRIN), a group of researchers sponsored by NCI, launched the largest study

ever to compare conventional and digital mammography. The Digital Mammographic Imaging Screening Trial, involving 49,500 women in the United States and

Canada, will compare digital mammography to standard film mammography to determine how this new technique compares to the traditional method of screening for

breast cancer.

Magnetic Resonance Imaging.—An imaging modality making use of a magnetic

field and radio-wave signals linked to a computer to create detailed images of areas

inside the body without the use of radiation. Each MRI produces hundreds of images of the breast from side-to-side, top-to-bottom, and front-to-back. A radiologist

then interprets the images. Breast MRI is not used for routine breast cancer screening, but clinical trials are under way to determine whether MRI is valuable for early

detection in certain groups, such as young women at high risk for breast cancer and

women with a previous history of breast cancer.

Positron Emission Tomography.—PET creates computerized images of chemical

changes that take place in tissue. NCI-sponsored researchers are evaluating the

usefulness of PET to detect tumors in dense breasts. A clinical trial is also evaluating the usefulness of PET results compared with the findings from other imaging

and diagnostic techniques. This trial is also studying the effectiveness of PET in

tracking the response of a tumor to treatment.

Computed Tomography (CT).—Computed tomography creates a series of detailed

cross-sectional x-rays of areas inside the body taken from different angles. The images are then turned into two- and three-dimensional pictures by a computer program. This technique is also called computerized tomography (CT) and computerized

axial tomography (CAT). Several NCI-funded investigators are studying the use of

dedicated breast CT devices as both a screening and diagnostic tool for the detection

of breast cancer.

Magnetic Resonance Spectroscopy (MRS).—MRS has the ability to distinguish cancerous tissue from normal tissue and benign growths. MRS can show the presence

and relative quantities of the chemicals comprising tissues of each type, and can

characterize even small tumors. As a result, MRS can make it easier to detect

breast cancer at even earlier stages. A number of NCI grantees are exploring use

of MRS in breast cancer.

Optical Imaging.—Optical imaging refers not only to the use of visible light but

also to radiation just beyond the visible—ultraviolet and near-infrared. Several researchers are evaluating the potential of using visible or near infrared light to scan

the breast for abnormalities alone and in conjunction with other imaging technologies and the possibility of combining such information with other techniques.

For example, NCI is supporting projects that superimpose optical signals from small

breast cancers onto MRI scans of the breast.

Computer-Aided Detection (CAD).—CAD involves the use of computers to bring

suspicious areas on a mammogram to the radiologist’s attention. Through a number

of grants, NCI is funding research that will develop computer-aided diagnosis methods to assist radiologists in diagnosing breast cancer from mammograms. It is hoped

that CAD will improve radiologists’ ability to interpret mammograms so that both

the number of missed cancers and the number of women unnecessarily sent to biopsy can be reduced. A number of grantees are exploring the use of CAD in breast

cancer. Currently, there are two FDA- approved CAD methods that are commercially available.

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Imaging Agents.—The NCI’s Development of Clinical Imaging Drugs and

Enhancers (DCIDE) program will foster and speed the development of promising imaging agents, such as contrast agents, and their translation from laboratory to clinic. NCI will make its pre-clinical development resources available to competitively

selected developers of a promising diagnostic agent or probe in order to remove a

recognized barrier between laboratory discoveries and their entry into the clinic. To

further aid in the development of promising imaging agents, NCI is launching a program to fund early clinical trials of novel imaging probes and agents. One of the

agents under development in this program is a nanoparticle that specifically targets

angiogenic vessels. This could potentially play a role in cancer detection, staging,

and monitoring of therapy for breast cancer.

In addition to imaging technology, NCI is investing in new biologic tests to improve our ability to identify cancer cells in their earliest possible stages of development. Among the research being supported:

Molecular Analysis.—NCI’s Innovative Molecular Analysis Technologies Program

(IMAT) supports the development of non-invasive techniques for identifying molecular changes that distinguish cancer cells from normal cells. More than 100 research

projects are under way, focusing on new approaches to analyze DNA, RNA, and proteins.

Proteomics: Finding Protein Patterns.—Proteomics is the systematic study of protein expression and function. In the Clinical Proteomics Program, a joint initiative

of NCI and FDA, researchers are discovering differences in patterns of protein in

the blood from cancer patients compared to people without cancer and applying this

knowledge to early detection of breast cancer.

Biomarkers.—NCI’s Early Detection Research Network (EDRN) is the first comprehensive network to develop and validate early detection markers for cancer. Researchers are studying a variety of molecules, proteins, genes, and other biological

substances that may be the earliest warning signs that normal cells are on the road

to becoming cancerous. Their discoveries are then translated into methods for detecting warning signals, sometimes even before full-blown cancer can develop.

Finding Fingerprints of Cancer Cells: The Molecular Classification of Tumors.—

All cells have unique ‘‘signatures’’—special characteristics related to which genes

are active and which proteins or other products the cell manufactures. During the

transformation of a normal cell to a cancer cell, the cell’s signature changes, and

the change becomes a signal of the presence of cancer. Researchers are developing

profiles of molecular alterations in human tumors, such as breast cancer, using

DNA, RNA, or protein-based technologies. This technology holds promise for improving the early detection, diagnosis, and treatment of cancer.

Over the years, researchers have focused on examination of cells shed by breast

tissue into the ducts. Investigators have now developed techniques for collecting nipple aspirates and ductal lavage and hope that it may be possible to evaluate suspicious breast masses detected by mammography by analyzing these secretions. It

may be possible to spare at least some women the need to undergo a surgical biopsy.

These are by no means established techniques, and it would be more accurate to

say that they are being ‘‘explored’’ rather than ‘‘used’’ in breast cancer diagnosis.

There are now a number of investigators around the country who have methods that

enable them to collect these specimens, but there is no consensus yet on how they

should be analyzed. The NCI is currently funding research through its exploratory

grant programs to determine which substances or characteristics of cells present in

these specimens will correlate reliably with the presence of absence of cancer in the

breast. The research also includes development of new analytic technologies to detect particular alterations. This research has not yet progressed to a stage where

large-scale clinical trials are ready to proceed.

NCI also supports a number of resources for the research community ranging

from tissue banks to registries to shared funding for national monitoring programs.

COMMUNICATING ABOUT MAMMOGRAPHY

It is not enough to make discoveries. We also must turn those discoveries into

interventions that benefit people and communicate that information so women can

use it to make important decisions about their health. The investments that NCI,

ACS, CDC, and AHRQ made in the 1980s and 1990s led to effective interventions

to enhance use of mammography. There is a solid armamentarium of effective interventions, and we have seen the former Black-white differences in mammography

use disappear. There still is under-use of mammography among some groups, including older and Hispanic women. We are now working with the CDC, ACS, and

other organizations to disseminate the effective interventions.

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NCI has several projects in place to improve the ways we communicate the results

of research and to take advantage of new communication technologies. One example

is a research project funded by NCI and AHRQ studying how to communicate about

the benefits and limitations of screening tests. Researchers are also developing tools

to help women ask the important questions and to examine their own preferences.

These research efforts are exploring the capacity of new communication technologies, including online and other interactive health communication tools, to address women’s questions.

CONCLUSION

Multiple factors come together in an equation that leads to longer and better lives

for breast cancer patients. All of our current tools are important, and all must be

improved because the outcome, although better than in the past, is not yet what

it should be. We must retain what is adequate and appropriate but strive to discover what is better. Many of the new technologies now under development hold

real promise. Detecting the molecular changes that lead to cancer will give us the

opportunity to intervene in the disease process more effectively. Like you, I am impatient for these new approaches to prove themselves. The lives of our mothers,

daughters, wives, sisters, and friends are at stake. We cannot allow ourselves to become complacent, accepting the status quo. Yet, we must not ignore the fact that

our best available technology today, mammography, does save lives.

I thank you for this opportunity to testify about this vitally important topic. I will

be pleased to respond to your questions.

Senator MIKULSKI. Thank you very much, Dr. von Eschenbach.

I just want to be sure—it is the National Cancer Institute’s position that women should continue to get annual mammograms

starting at age 40?

Dr. VON ESCHENBACH. Every one to 2 years, Senator, is our recommendation. Whether there is a difference between every year or

between one and 2 years is still not absolutely determined, but at

least every one to 2 years.

Senator MIKULSKI. Thank you.

You are familiar with the Danish study done by two very eminent biostatisticians. Because of logistics, they could not come

today, although we acknowledge the cooperation of the Danish Embassy, and with unanimous consent, I am going to enter their study

into the record.

[Document follows:]

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Senator MIKULSKI. My question is this, Doctor. You have read

the Danish study of Drs. Olsen and Gotzsche, and also the PDQ,

which is really an advisory board to the NIH and NCI, has also

raised yellow flashing lights. Could you give us your comments and

analysis of the Danish study, and if you care to comment on PDQ,

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from which a board member will testify later. You have just said

it clearly, and the position has been clearly since 1997. We welcome

your commentary on these two studies that essentially dispute

what you have just said.

Dr. VON ESCHENBACH. In summary, the investigators that you

address looked at the seven randomized trials, made decisions

about certain aspects of those trials in terms of how much they

would weight them or include them in a combined analysis of the

information called the meta-analysis. Based on their judgments

and decisions about the relative value of some of those studies,

they eliminated some of them from the ultimate analysis. Then,

when they applied their meta-analysis, they concluded that the information was not significant enough to warrant continued support

of mammography.

Other statisticians, other experts, have looked at their analysis

and have raised concerns about many of the judgments that they

made on a statistical basis. So there is a difference of opinion

among the experts as to how one should evaluate those seven combined trials.

Other experts have looked at that information and have concluded, as the U.S. Preventive Services Task Force has, that the

data still supports the value of mammography in the equation that

I pointed out and must continue to remain an important part of

that equation.

So the issue here, Senator, is a difference in statistical interpretation and methodology. From the scientific perspective, there is

value in that argument. From the clinical perspective, however, one

must conclude that there is no indication that mammography

should not be in that equation based on that analysis, even if you

might want to argue whether it is providing the major part of that

equation or a component of it.

Senator MIKULSKI. Doctor, I have time for one more question. Essentially what you are saying is that one group of biostatisticians

came to one set of conclusions and another has come to another,

both competent people.

Dr. VON ESCHENBACH. Correct.

Senator MIKULSKI. We are now again into lack of clarity—I am

not saying from you—and my question is do you think—there have

only been seven studies over 40 years in terms of the efficacy of

mammograms in early detection—do you think it is time to do another study?

Dr. VON ESCHENBACH. No, I do not.

Senator MIKULSKI. Could you comment on that, because it would

then seem like we need a study to settle the disputes about the

other studies.

Dr. VON ESCHENBACH. Those studies over that period of time enrolled over 400,000 patients, and over that period of time, much

has changed with regard to the State of the art of mammography

and our State of the art with regard to breast cancer care.

To attempt to repeat that kind of study in which there would be

a randomization whereby women by the flip of a coin or by chance

would be assigned to either mammography or no mammography

would not at this point in time be a viable or rational study, in my

opinion, one that would not likely be able to be carried out at this

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point in time and certainly not, I believe, under our current structure.

Senator MIKULSKI. But, Doctor, isn’t that true of any clinical

trial? Some get the treatment, and some do not; some get the diagnosis, and some do not.

Dr. VON ESCHENBACH. In terms of being able to attract a sufficient number of patients to the trial and in terms of being able to

get them to accept a randomization by the flip of a coin as to

whether they would or would not get mammography, I have and

I believe others have serious concerns that that kind of trial could

not effectively be carried out in a reasonable period of time to get

a conclusive answer to the question; while in the meantime, where

we believe we should be focusing our efforts is on even better methods of detection than mammography and to look at newer technologies and their applications in the kinds of clinical trials you are

describing.

Senator MIKULSKI. You raise a very good point. Unfortunately,

my time is up. I think other of my colleagues will raise other

issues. But I thank you; I think we are on our way to clarification.

Senator Harkin?

Senator HARKIN. Thank you, Senator Mikulski.

I have looked very carefully at the study that was done by Olsen

and Gotzsche, and it seems to me that first of all, these were

mammographies that were done in the 1960’s and 1970’s and

maybe in the early 1980’s. I do not know if they got into the 1980’s

or not, but it was sometime in that time frame. As you have stated,

we clearly have better mammography technologies now than we

had at that time.

Second of all, Olsen and Gotzsche, as I understand it, looked at

the technical details of how the studies were set up. If I am not

mistaken, others have looked at their study and basically refuted

some of their findings based upon what happened later on in the

clinical trials. I am sorry, I am just a layman speaking here—I am

not a doctor or a biostatistician or anything like that. But it seems

to me, as I read through their study, that Olsen and Gotzsche,

looked at one part of the data from the clinical trials, and based

upon that, they said there was not conclusive evidence of the value

of mammography. They did not really look at all the data. At least,

that is my layman’s way of interpreting it. And based upon some

statistical analysis they had done about how the groups were selected and who was screened and who was not screened, they

reached these decisions. But they did not take into account that

those things were adjusted for, if I am not mistaken, later on.

Those anomalies, whatever they might have been, were adjusted

for later on.

Am I somewhat correct in that?

Dr. VON ESCHENBACH. Yes, Senator, you are quite on track with

regard to your interpretation, as I also see it, and I believe that on

the next panel, there will be experts far more sophisticated than

I with regard to biostatistics. But I am in agreement with your interpretation.

Senator HARKIN. I know that to the general public this sounds

like a lot of gobbledegook, and it is sometimes beyond my comprehension, too. But if you read the Danish study and really get

34

into it, I am finding out that they just looked too narrowly at the

data from the clinical trials. Second, they did not take into account

the new technologies and the development of better mammography

screening that we have today.

Now I want to follow up on what Senator Mikulski was just getting to when her time expired. She spoke about future methods of

breast cancer screening and new types of technologies. Could you

elaborate a little bit on that and perhaps the time frame we are

looking at?

Dr. VON ESCHENBACH. At the present time, the National Cancer

Institute is supporting one trial that is looking at the value of digital mammography versus standard mammography as a method of

improved detection. Other technologies that are being evaluated include PET scanning, or the use of positron emission tomography,

and the evaluation of the function of lesions; magnetic resonance

imaging is also being employed; and techniques whereby we are beginning to understand the biologic basis of tumors; even aspirates

from the nipple that enable us to look at cells may be a way of detecting cancer in its earlier stages.

So there are multiple methodologies that are being evaluated in

the kinds of trials that Senator Mikulski is referring to.

Senator HARKIN. Dr. von Eschenbach, the National Cancer Institute recently announced the development of a new blood test—for

detection of ovarian cancer. I believe it is a blood test that patients

can take.

Dr. VON ESCHENBACH. Correct.

Senator HARKIN. Is there anything underway in terms of research that might lead to some kind of blood test for early detection of breast cancer?

Dr. VON ESCHENBACH. Well, that is one of the methodologies

that, as it is validated in ovarian cancer, needs to be more broadly

applied, and the underlying technique certainly opens up the hope

that this would be applicable to many cancers, including breast.

Senator HARKIN. Of course, the ultimate goal of all the money

that we have been putting into breast cancer research is to hopefully find a means of prevention, a vaccine or some other treatment

that would be a preventive measure for breast cancer. Is there anything along those lines that you can tell us about?

Dr. VON ESCHENBACH. I think that what we are looking at, Senator, in that equation is that we would like to attack this problem

at multiple places along the spectrum, including the ability to prevent it. We now know that there are agents that have been developed that can be preventive for breast cancer; tamoxifen and

relaxifen are being clinically tested, and new drugs are also being

developed that would perhaps have less toxicity, yet at the same

time be able to provide that preventive effect as well.

So I want us at the National Cancer Institute to have a

multipronged attack or approach that looks at detection, diagnosis,

treatment, and prevention, so that ultimately, we eradicate the

deaths that we are seeing from this disease.

Senator HARKIN. Thank you, Doctor.

Senator MIKULSKI. We have now been joined by Senator Bill

Frist, the only physician currently serving in the U.S. Senate, who

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has brought such keen insight to all of our committee deliberations

and is the ranking member of the Public Health Subcommittee.

Senator Frist, I would like to turn to you. Senator Specter was

here, but he had a meeting with the Steel Caucus with the President, and Senator Snowe was unable to come. So we are glad to

see you.

Senator FRIST. Thank you. I would just ask that my opening

statement be made part of the record, and I apologize for being a

few minutes late.

Senator MIKULSKI. Without objection.

[The prepared statement of Senator Frist follows:]

PREPARED STATEMENT OF SENATOR FRIST, M.D.

During the past few weeks, there have been seemingly conflicting

and often confusing reports about the benefits of mammography

screening. I believe today’s hearing will go a long way toward providing more clarity. It is important that women have as much credible information as possible about mammography as a breast

screening tool so that they can make informed and appropriate decisions about their health.

I want to extend a special welcome to Dr. Andrew von Eshenbach

of the National Cancer Institute. I understand that this is your

first time testifying before Congress. I am very pleased that you

are here today.

It is confusing for many Americans to read a report in the local

paper 1 week about a recent study stating that mammography may

not be beneficial, and then to read statements by public officials

the next week stating that the government still recommends

mammographies. Women can easily be confused about what they

should be doing in the interest of their own health.

In many ways, it would be easier to communicate with the public

about how to take care of their health if there existed one static,

scientific document which stated exactly what should be done, by

whom, at what time, and at what place. However, science is a constantly evolving field, with new information being added daily regarding new therapies and new ways of looking at diseases. As we

gain more information about how to diagnose, treat, and or even

cure many illnesses, we must interpret new research, evaluate it

in the context of other studies, and challenge our scientific and

medical assumptions.

Unfortunately, making the right health care choices becomes particularly difficult when there are conflicting research studies. During those tumultuous times, we generally rely on public health and

health care experts to assist us in wading through the information

and drawing appropriate conclusions, to provide guidance to the

general public about appropriate health care choices. For mammography, the story is no different. Scientists and statisticians have

been debating the relative merits of mammography as a screening

tool for a number of years. In the mid-1990’s, for example, there

was a great deal of controversy over whether women in their 40’s

should receive mammographies. After more definitive studies became available and were analyzed, the National Cancer Institute

eventually decided to recommend screening for women in their 40’s.

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Last fall, the issue once again came front and center when Danish scientists reviewed seven leading studies of mammography

screening and concluded that there were significant questions

about the quality of the research—ultimately questioning whether

using mammography as a screening tool results in a reduction of

breast cancer deaths. This one study produced a flurry of discussions about the validity of mammography as a screening tool and

the message that we should be sending to women about its value.

However, as is the case with all studies, research must be put in

the context of what has already been learned.

That is why I was encouraged when the U.S. Preventive Services

Task Force, an independent panel of experts in primary care and

prevention that systematically reviews the evidence of effectiveness

and develops recommendations for clinical preventive services, last

Thursday released new recommendations regarding mammography, based on a review of eight randomized, controlled trials.

These recommendations call for screening mammography with or

without clinical breast examination, every two years for women

ages 40 and older, as well as clarifying recommendations regarding

breast self examinations. Their previous recommendations, in 1989

and 1996, endorsed mammography for women over age 50.

Although the Task Force’s recommendations provide guidance

about the overall value of mammography for breast cancer screening, it does not endorse mammography as the perfect screening

tool. We need continued research to improve the detection of breast

cancer lesions and differentiation between cancer lesions and other

non-cancerous lesions. Moreover, as better diagnostic tools to detect

early-stage tumors are developed, additional research will be needed to guide our decisions about recommended treatment options.

Finally, as we all are aware, the answer is not just to detect breast

cancer but also to both prevent the incidence of the cancer and to

appropriately treat any detected tumors. We must work to not only

diagnose, but also to prevent and cure the diseases.

Additionally, we must continue efforts to ensure that women receive quality mammography services without reducing access to

those services, which is why it is important that we strengthen the

Mammography Quality Standards Act (MQSA). I appreciate the

testimony from the National Breast Cancer Coalition and the

Susan G. Komen Foundation about this vital program, and I look

forward to working with Senator Kennedy, Senator Gregg, Senator

Collins, and my other colleagues on this Committee to reauthorize

this important law.

Senator FRIST. First of all, welcome, Dr. von Eschenbach. I know

this is your first hearing. The position that you have assumed is

one that is very, very important to millions and millions of Americans, as you well know. I appreciate your sacrificing a practice of

taking care of patients one-on-one for public service, for what is a

terribly important position and initiative. Whether it is in the Patient Bill of Rights or coverage of clinical trials for cancer or for

preventive medicine or for Medicare reform modernization, what

we do with cancer is right at the center of all of these debates. I

am delighted to have you before us today, initiating that discussion, so people can get to know you and you can get to know them.

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You and I have had the opportunity to talk about a number of

issues. Mammography is an issue that we are spending a lot of

time on today and a very important issue that, as has been mentioned, has been debated and discussed again and again—we are

going to continue to discuss it to find just the appropriate place. As

I can see from your chart, we see the change in mortality and the

various parameters that are there. A and B will continue to

change, as will C, over time, and that is the importance of these

hearings.

In my couple of minutes, let me just ask you to expound a bit

on translational research. I think it is very important—and I know

that you feel very strongly about it—to make sure that the basic

research findings that are so remarkable, that we have invested in

in a doubling fashion at the National Institutes of Health, are

translated into the types of diagnostic and treatment procedures,

like mammography, like treatment for breast cancer.

Could you share with us a little bit of your philosophy and what

you hope to see happen; feel free to use mammography as an example of the importance of translational research.

Dr. VON ESCHENBACH. Thank you, Senator. I would be delighted

to share that with you, and I think that breast cancer is a very important example of the opportunity and the challenge that

translational research provides us.

Specifically, one of the problems with mammography is the question as to whether we are detecting some breast cancers that, by

their very nature, would not be virulent or aggressive and would

then threaten a patient’s life.

We do not yet have a way of being able to accurately, totally,

completely determine or predict that, so we must treat any cancer

that we find as a dangerous cancer requiring significant intervention.

Hopefully, as we begin to understand how cancer cells develop at

the genetic level and why they behave the way they do based on

their interactions with other cells, when we understand that at the

basic, fundamental, biological level, we can design interventions

that can interfere with, change, or alter that behavior, and we may

then be able to use that information to define the aggressive cancers, treat them aggressively, to find the cancers that do not have

those molecular-genetic characteristics and treat them in a more

benevolent but effective fashion.

So translational research will significantly improve the rational

application of our treatments.

Senator FRIST. And what will that do to the protocols, and what

can be recommended? How will that change those protocols?

Dr. VON ESCHENBACH. One of the important ways that I think it

will change the protocols is that before a patient enters into a protocol, we can use the molecular and genetic information to stratify

them, if you will, to separate them into high-risk and low-risk

groups and then apply the particular treatment strategy or the protocol that we are testing; but we will know much more precisely

the basis upon which we are gathering that information.

Senator FRIST. Thank you.

Madam Chairman, I think I will forego; I know we have a number of other panels to hear from.

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Senator MIKULSKI. Thank you very much, Senator. That was an

excellent question.

I would now like to turn to Senator Jack Reed.

Senator REED. Thank you very much, Madam Chairman.

Thank you very much, Doctor, for your testimony. At the core of

today’s hearing is a controversy about the efficacy of mammography in screening. Stepping aside from that, besides the advice

that you are giving women today to continue the screening, is there

other advice that you might give in terms of perhaps starting

younger in terms of screening, or a different approach to it that

would avoid the question of the efficacy of the tests and the statistical debate we are having today?

Dr. VON ESCHENBACH. No, Senator. We set the threshold at 40

as what we believe to do the optimal or reasonable level at which

we can recommend it and apply it. Now, again, the research that

I alluded to earlier in terms of understanding the disease will hopefully lead us to be able to identify women who are at much higher

risk than normal or average, and in those women, we may need to

modify or change the recommendations as we go forward so we can

detect them even sooner or earlier. But that is a work in progress,

and we have not yet reached the point where we can make it a uniform recommendation.

Senator REED. You have experience in several different medical

conditions, cancer, etc. Is there a similar controversy in other

areas, for example, in terms of prostate or other cancers, where the

testing regime and the efficacy are also debated as they are with

mammography?

Dr. VON ESCHENBACH. Yes, sir, unfortunately, there are, and I

personally was deeply involved in the issue of formulating guidelines for men for the use of prostate-specific antigen. As with mammography, in that situation, there is even less data or information

upon which to make hard, specific, scientific recommendations.

I think what we are faced with as clinicians responsible for the

lives of patients with cancer is to apply the science, but at the

same time use clinical judgment and arrive at the best recommendation we can today given the information that we have.

The information on mammography is far better than the information for PSA and prostate cancer, and we are basing our recommendation to American women on what we have available as

the best information.

Senator REED. But I would suspect that both of these areas have

helped in terms of your analysis, that having experience in several

different fields has helped inform your judgment about your recommendation today.

Dr. VON ESCHENBACH. What is most gratifying to you and to us

is the fact that in both of these diseases, we are seeing a decline

in mortality; we are seeing a decline in death rate. That gives us

hope and a bit of comfort that we are at least on the right track.

We are nowhere near where we need to be, but we are heading in

the right direction.

Senator REED. Finally, Doctor, you indicated in your testimony

the disparity between the incidence of in African American women

and white women, Caucasian women. What role does mammogVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00042 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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raphy play in this disparity, and what might be other contributing

factors?

Dr. VON ESCHENBACH. There are two very interesting observations that can shed some light on the answer to that question. One

is that we are beginning to see the gap narrow between the mortality rate for black women and white women, so we are improving,

we are closing that gap, and we are making progress. That coincides with the fact that there has been greater utilization of mammography among black women. So that hopefully, those are coincident. I cannot prove them to be cause and effect, but they are coincident, and they are both encouraging.

Senator REED. Thank you. One final point, Doctor. I do not know

much about South Philly, but are you the only von Eschenbach in

South Philly?

Dr. VON ESCHENBACH. My mother’s maiden name was de Alfonso.

Senator REED. Now I understand, now I understand. Thank you,

Doctor. The record is now complete. I yield back.

Dr. VON ESCHENBACH. Thank you, Senator.

Senator MIKULSKI. Senator Murray?

Senator MURRAY. Thank you very much, Madam Chairman, first

for having this hearing, which I think is so important today, but

also for your long-time work on the issue of breast cancer. We have

been here before, debating this issue—Senator Hutchison remembers—and frankly, we have been through it too many times, and

I think the bottom line is that women need to know what they can

do to fight breast cancer, and unfortunately, this debate too often

comes down to a debate between numbers versus women, and we

have allowed abstract statistical data to confuse and distort the

issues.

I want to thank all the witnesses who are here today, especially

the advocates, for the tremendous work that you do on behalf of so

many women. I appreciate your continuing efforts to make sure

that women have access to early screening and diagnosis.

Madam Chairman, it seems to me, unfortunately, that we have

allowed this controversy to shift the focus away from prevention

and access to health care. This is not just an issue for women in

their 40’s or 50’s, but for women who are in their 20’s and 30’s who

want to know what they can do today to prevent breast cancer. I

hope we do not lose our focus on that issue.

One issue that concerns me very much is that we do know that

through better information and access, more women are getting

regular mammograms, and we know that that has helped to boost

survival rates; but we also know that access has not improved

equally across the board for all women. Minority women have a

much lower screening rate; in fact, the screening rate for Asian and

Native American women is really dismal. I know there are many

factors that contribute to those low rates, but I am very worried

that the current conflicting and confusing messages are not going

to help our efforts to expand access.

Doctor, if you could just tell me what you think we need to do

to make sure that this current controversy does not hinder our efforts to improve access for minority women, I would appreciate

hearing your thoughts on that.

Dr. VON ESCHENBACH. Thank you, Senator Murray.

40

We have tried to be very clear in our message so that we do not

continue to contribute to some of the concern. At the same time,

we are paying a great deal of attention within the National Cancer

Institute, particularly through Dr. Reimer’s division, to messages

and communication and education so that patients do in fact have

appropriate and timely and accurate information; and we are learning and studying how to reach out as effectively as we possibly can

to various communities so that we can provide that appropriate

message in the appropriate way.

Senator MURRAY. I think that that is extremely important to do.

Especially when information that comes out that is conflicting, it

automatically offers women the excuse that they are looking for. So

I think we need to especially now, at times like this, reach out

again and make sure we are doing and saying what we need to do

to make sure that women get screened.

Let me ask you another question. We always focus on what age

do you start having a mammogram every year, and we need to

really get that message out; it is very important. But I am also

very concerned about what we should be telling women who are in

their 20’s about what they can do now, before they start worrying

about getting a mammogram when they are 40. What are we learning today that women can be doing even when they are young teenagers that will help decrease their risk of getting breast cancer?

Dr. VON ESCHENBACH. Well, we do not have the absolute cause

and effect kinds of relationships where we can say that if you absolutely do this, we can guarantee that you will not have a problem.

But we do recognize certain associations—for example, diet being

one of them—and we are obviously encouraging a healthy lifestyle

with regard to diet and exercise as part of that preventive process.

What we need to do is research that will help us identify women

who are at high risk early in life and also identify the most effective preventive methods, not just in terms of lifestyle but some of

the biologic interventions that are safe and appropriate. Our whole

area of cancer prevention is directed toward trying to identify those

kinds of interventions and then apply them appropriately in

women at high risk.

Senator MURRAY. Good. I really appreciate that, and I hope that

we do not allow these kinds of discussions to refocus away from

making sure that we are doing that, because I really think that

that is the much better answer in the long run, what we can do

when we are younger so that breast cancer is not such a concern

for women who are older.

I have one other comment and question. I think there is another

issue that has really been ignored in this debate, and that is the

role that mammography has played not just in improving survival

rates but in improving quality of life for breast cancer victims. The

written statement of Dr. Leffall, who is the chair-elect of the Susan

G. Komen Breast Cancer Foundation, shows that because of mammography, tumors have been detected earlier and smaller.

Now, that is a huge benefit that I think has been lost in this debate, because options to mastectomy significantly improve quality

of life and allow for a faster and quicker recovery.

Can you talk a little bit about how mammography and early diagnosis have impacted quality of life for breast cancer patients?

41

Dr. VON ESCHENBACH. Thank you for pointing that out. I think

that from the quality of life point of view, over and above just the

mortality argument or discussion that we have been having, from

the patient’s point of view, that is an extremely important contribution. By detecting cancers earlier, one can then apply therapies

that are going to be less mutilating and have less of an impact on

quality of life, and that in itself is a major goal and objective for

us. So I concur completely with your emphasis on that particular

aspect of the issue.

Senator MURRAY. Thank you very much, Doctor. I really appreciate your coming and providing the testimony today.

Madam Chairman, again, I really want to thank you for holding

this hearing to clarify this issue once again and to help us focus

on what we can do to make quality of life better for all women in

this country.

Senator MIKULSKI. Thank you very much, Senator Murray, for

your compliments but most of all for your ongoing advocacy.

I invited the two Republican women who are not on the committee to join us today because of their longstanding advocacy on this

issue. As I said, Senator Snowe and I have worked on this since

we were in the House, but Senator Kay Bailey Hutchison is here,

and Doctor, you will be interested to know that the women of the

Senate have really worked on women’s health on a bipartisan basis

and particularly on the issues of breast and ovarian cancer. Senator Kay Bailey Hutchison has been an advocate in helping me get

the Mammogram Quality Standards that were necessary, and of

course, she is from the home State of the outstanding Komen Foundation. And also, you are on the Labor-HHS Committee on Appropriations, so you are also a member of this. I am sorry.

Senator HUTCHISON. That is right, Madam Chairman, and you

and I, of course, have worked on many cancer issues and trying to

fund cancer research.

But to give you the real background—I feel like it is deja vu all

over again—in 1994, the Government representative came forward

and said women should not have mammograms until they are 50.

Well, Senator Mikulski called a hearing, and every, single woman

Member of the Senate came and upbraided the Government official,

who was sitting at that table by himself just like you are, and said

how could you send this kind of mixed message. We have been

working for years now to at least get early detection for women, because that is all we have—we do not have the cure—and finally,

after about a month or so after that hearing, the entire NCI

cratered, and everybody said, ‘‘No, no, no—40—we think that is

probably the most prudent thing to do. Women should have mammograms at the age of 40.’’

Well, fast-forward to about a month ago, and we see the results

of the study that say that mammograms are really useless and

might even cause harm. I was looking at that, just astonished that

we could be once again mixing our message based on, apparently,

trials that were done in 1985. Now, there may have been other

things that went into that, but we are talking about 1985 trials,

and we are saying, well, you can do without a mammogram, and

maybe walking is just as good as getting a mammogram.

42

Well, here we are again, and Dr. von Eschenbach, I am so glad

that you have clarified very quickly that 40 is the recommendation,

because I know that we have saved lives. Everyone in this room

knows that by early detection, we have saved lives. We also have

put hundreds of millions of dollars into research to try to find the

cure, and you will be in a pivotal position to help us find that cure

so that we will not have to talk about mammogram anymore; we

will cure this, and then perhaps we will not have to deal with cancer of this kind again, and we can move on to something else.

But for now, I would ask you how you view this study that is

based on these 1985 trials that came from the Danish researchers

that would indicate that false positives are a reason not to go forward and do the only thing we know that will allow the early detection of a cancer tumor.

Dr. VON ESCHENBACH. There are two answers that I might offer,

Senator. One is that certainly as we have improved the technology

of not only mammography, but the ancillary studies that can be

used to follow up mammography, including the ability to biopsy

under ultrasound, we have actually been able to improve on the

false positive concern, if you will.

So I think that additional progress is improving some of those

previous concerns and issues.

The other thing that I think your question comes out, to come

back to my example, is that we are seeing a decline, and if you

want to use the number 6 per 100,000 as that decline, one could—

and I think the debate has been around whether it is 3 plus 3

equals 6, or 2 plus 4 equals, and there is an argument around the

relative value of mammography—but I believe we all conclude that

mammography needs to be a part of that equation, that it is continuing to add to that equation, and whether there is an argument

among statisticians as to whether it is 3 plus 3 or 2 plus 4, the important point is that it is contributing and must remain a part of

the equation.

Senator HUTCHISON. Anyone who has had a mammogram knows

that you wonder which is worse—getting the mammogram or getting the cancer—but having said that, is there anything harmful

that can be done in a mammogram, or maybe a wrongly given one,

but is there in general a harmful effect of a mammogram?

Dr. VON ESCHENBACH. I believe that the greatest issue is in fact

the discomfort and the humiliation that may go along with the examination, but other than that, other harms would be negligible,

in my opinion.

Senator HUTCHISON. Well, thank you, and I do hope that you will

use your position to help us find the cure, because that is what has

been missing for all these years that we have worked to try to

eradicate breast cancer as a leading cause of deaths among women.

Thank you.

Dr. VON ESCHENBACH. Thank you, Senator.

Senator MIKULSKI. Now we turn to Senator Clinton, one of the

newer members of the committee but certainly one of our most active.

Senator Clinton?

Senator CLINTON. Thank you very much, and thank you for holding this hearing.

43

And thank you, Dr. von Eschenbach, for now being in the hot

seat for quite some time. I appreciate your clarification—I am sorry

that I missed your testimony, and I just want to ask three brief

questions just to be sure that I can accurately report to my many

constituents who are deeply concerned about the controversy and

also about the high prevalence of breast cancer in many parts of

New York, higher than the national average.

Is it fair to say that your testimony today reflecting the NCI position is that all women should get regular mammograms after the

age of 40, or is it that women should be provided with information

about the benefits and risks which they then, in consultation with

their doctors, make their own decisions?

Dr. VON ESCHENBACH. We are recommending that it be a combination of both the performance and availability of the mammogram along with the education and understanding of the implications of it. I believe that both of those are important, but I would

not leave out the mammogram as a primary part and the initial

part of that recommendation.

Senator CLINTON. But a woman who is a potential recipient of a

mammogram really has no independent way of determining the efficacy or the quality of the mammogram; so if I am asked by a constituent after this hearing what did Dr. von Eschenbach say should

be done, what is my short answer?

Dr. VON ESCHENBACH. Beginning at age 40, you ought to have a

mammogram every 1 to 2 years.

Senator CLINTON. OK, great. I just want to be absolutely clear

about that.

As to the second issue with respect to the quality and the efficacy, we will be reauthorizing the Mammography Quality Standards Act, recertifying it, I think this year. Will you be able to provide us with specific suggestions as to any modifications of the Act

that might be helpful to address this controversy and increase the

quality standards? I think there has been some debate about

whether or not the MQSA has really lived up to its promise. Can

you offer any suggestions as to what we can do to modify it when

we reauthorize the Act?

Dr. VON ESCHENBACH. At this point, I could not, Senator, but I

would be happy to provide that to you in subsequent information

and material that would give you the kind of documentation that

you need for an intelligent recommendation from me.

Senator CLINTON. That would be very helpful, because one of the

things which is happening in New York, and I assume it is happening elsewhere, even before the back and forth of the last month or

so, is that many physicians’ offices and freestanding mammography

clinics were eliminating the service because the reimbursement

was insufficient to pay for the physician time, the technician time,

and the overhead costs.

So we have many parts of my State where it is very difficult to

access a mammogram, and what I am worried about is that in light

of this controversy, we will see more and more insurance companies determining that they will no longer cover the cost of mammography, concluding that because it is somewhat in dispute as to

its importance, it is no longer a covered service.

44

So I am hoping that your very straightforward statement that it

is still the recommendation of the National Cancer Institute that

women, staring at the age of 40, have mammograms, will give us

the ammunition we need to avoid further cutbacks in access and

reimbursement, which I am very concerned about.

So I join the other members of this panel in thanking you for

your testimony, thank you for taking on such an important task,

because certainly those of us who have been involved in this issue

for some time—and I see my friend Fran Visco out there—know

that we have to do even more to find ways of preventing and curing

breast cancer and that mammography is a tool in that fight, but

it is not the principal weapon that we need to utilize.

So thank you very much for being here.

Dr. VON ESCHENBACH. Thank you, Senator. You said it far better

than I did. Thank you.

Senator MIKULSKI. Thank you very much, Dr. von Eschenbach.

If you would like to hang around, we would really welcome you at

the end, perhaps, if you have any concluding observations.

Dr. VON ESCHENBACH. Thank you, Senator.

Senator MIKULSKI. I will say to my colleagues that we have two

excellent panels, one that we will call up now, which includes Dr.

Donald Berry and Dr. Harmon Eyre.

Dr. Berry is from the PDQ, and Dr. Eyre is from the American

Cancer Society. They will be followed by a panel that will include

the National Breast Cancer Coalition, a clinician representing the

American College of Obstetricians and Gynecologists, and also a

physician representing the Komen Foundation.

Dr. Berry is an international expert and is the chairman of biostatistics at the University of Texas. He is also a principal investigator on a project funded by the National Cancer Institute to assess the relative contribution of screening mammography,

tamoxifen, and chemotherapy in terms of the drop in breast cancer.

We invited Dr. Berry to come and speak as a member of the Physicians’ Data Query Screening and Prevention Board, the PDQ,

which has raised some yellow flashing lights about the efficacy of

mammograms.

Dr. Harmon Eyre has a career-long interest in cancer research.

He comes to us with an academic career in medical oncology. He

has degrees from Utah and Hopkins. He has been recognized by

the American College of Surgeons. We really welcome him to

present the views of the American Cancer Society.

Dr. Berry, we would like you to kick the panel off and give us

the perspective of the PDQ, and then we will turn to questions.

STATEMENTS OF DR. DONALD A. BERRY, CHAIRMAN, DEPARTMENT OF BIOSTATISTICS, M.D. ANDERSON CANCER CENTER,

UNIVERSITY OF TEXAS, HOUSTON, TX; AND DR. HARMON J.

EYRE, CHIEF MEDICAL OFFICER AND EXECUTIVE VICE

PRESIDENT FOR RESEARCH AND MEDICAL AFFAIRS, AMERICAN CANCER SOCIETY, WASHINGTON, DC

Mr. BERRY. Thank you very much, Senator, and good afternoon.

Thank you for inviting me to this important hearing.

Just a word about Dr. von Eschenbach. I will say some things

that disagree with Dr. von Eschenbach. I had the pleasure of servVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00048 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
45

ing with him on the faculty at M.D. Anderson for 2 years, and as

a result of that have come to respect his opinion, his clinical abilities, and his person, and there is no one in medicine whose opinion

I respect more than his.

I serve on the PDQ Screening and Prevention Board. We discuss

published literature and decide how to modify our website accordingly. This website is used by physicians and the lab public, so

with respect to Senator Clinton’s question, the women in her State

can long onto the PDQ website and get information about screening

benefits and risks.

We assign levels of evidence to our statement. We are independent of the NCI. We are not advisory to the NCI. We do not establish guidelines. We do not make official recommendations.

At a recent PDQ meeting, we discussed as a matter of course this

paper that has been mentioned and referred to by Senator Mikulski and others by Olsen and Gotzsche that critiqued the randomized trials of screening mammography. We agreed with some of the

criticisms but not with all. Our current statement indicates that

the benefits of screening are uncertain, and based in part on this

study, the plan is to modify the statement to add that the existence

of a benefit is itself uncertain.

The deficiencies with which we agreed are discussed in detail in

my written report, which I ask to be included as part of the record.

In each case, there was evidence of a bias favoring screening, but

not all trials were subject to these biases.

Briefly, first, women with pre-existing breast cancer were preferentially excluded from the screening group. Second, attribution of

cause of death was not blinded. Third, in three of the Swedish

trials, the timing of the control mammogram slipped, increasing

the time to country breast cancer in the control groups. This is a

technicality which we can get into if you would like, but it is an

important bias. And fourth and finally, there have been no independent audits of the Swedish trials. In contrast, the Canadian

trial which showed no screening benefit has been thoroughly audited.

In my report, I explain how people can differ in their evaluation

of evidence toward screening. At least 90 percent of what we know

in medicine is the result of clinical observation, with the rest derived from randomized control trials. Experience is a great teacher,

but when inferring the benefits of screening, clinical observation is

flawed.

Women with breast cancer detected mammographically have extremely good prognoses—extremely good prognoses—in comparison

with those having cancers detected in any other way. But this does

not mean that screening reduces mortality in itself. I explain why

this is so in my report, and I discuss the associated biases. Hence

the need for randomized trials.

How impressive are the results of the trials? Suppose we ignore

the Canadian trial which showed no screening benefit and take the

results of the Swedish trials at face value. The most recent data

from Sweden show a 21 percent reduction in breast cancer mortality. This is a paper that has been accepted to appear and is currently under embargo by the journal, so I cannot be too specific

about it, but the 21 percent figure appeared in the press, and this

46

is a lowering of the 30 percent figure which occurred earlier, and

it applies to all ages; there is no distinction between less than 50

and greater than 50.

This is a relative risk reduction. One way to convert it into a

more meaningful absolute measure of risk is to ask the corresponding increase in life expectancy. Out to 18 years of follow-up in the

Swedish trials, this increase is about 4 days per women screened.

In contrast, quitting smoking adds years to life expectancy.

What should we tell women? The answer is the truth. The benefits of screening are uncertain, and women should know this; they

should be informed of the possible benefits and risks along with the

associated uncertainties and decide about screening for themselves.

I discuss the risks of screening in my report, and I hope you ask

me about that.

Where do we go from here? We cannot do another randomized

trial in this country—I completely agree with Dr. von

Eschenbach—but there are several steps that we can take, and

there are developments being pursued. One is that we should provide women with aids so they can make informed decisions about

screening. Second, the Swedish trial should be independently audited.

Third, there is an NCI-sponsored program called CISNET that

addresses the question that Dr. von Eschenbach put up on the

board regarding the decrease in breast cancer mortality, trying to

apportion the relative contributions of screening mammography,

hormonal therapy, and advances in chemotherapy.

The fourth is the most promising of all. We know little about the

biology of the disease, as Dr. von Eschenbach indicated, but we are

learning. Cancers may manifest their metastatic potential when

they are tiny, say, when they total only a few million cells, or they

may start sloughing off their tumor cells for traveling through the

rest of the body when they have become large enough to be detected mammographically. Screening would be effective in the second case, but not the first. We are learning fast about the biology

of the disease, and soon will be able to decide which.

I thank you for the opportunity to discuss this very important

issue in women’s health, a topic to which I have dedicated and will

continue to dedicate my career. I am happy to answer questions.

Senator MIKULSKI. Thank you very much, Dr. Berry.

[The prepared statement of Mr. Berry follows:]

PREPARED STATEMENT OF DONALD BERRY

EVALUATING THE EVIDENCE OF BENEFIT FOR SCREENING MAMMOGRAPHY

I serve on the PDQ (Physicians’ Data Query) Screening and Prevention Editorial

Board. We write statements for the NCI Website http://www.cancer.gov/cancerlinformation/ regarding screening for cancer and preventing cancer. However,

we are independent of the NCI. Our statements are intended for and are accessible

by physicians and the general public. We meet approximately six times per year to

discuss recently published literature and on the basis of the available information

we decide whether and how to modify our Website statements. We assign levels of

evidence to our statements. Contrary to reports in the press, we are not advisory

to the NCI, we do not establish guidelines, and we do not make official recommendations.

I will give my understanding of the discussions and intentions of the PDQ Board.

However, I have not been elected to be a spokesperson for the Board and so I do

not have the right to speak for other members of the Board.

47

My introduction to today’s topic was my appointment five years ago to an NIH

Consensus Development Conference Panel on Breast Cancer Screening for Women

Ages 40–49. 1 had no ax to grind then and I have none now. My life is dedicated

to understanding and fighting cancer—breast cancer in particular. I am intimately

involved in the prevention and treatment of this horrible disease. Nothing would

please me more—professionally and personally—than to have a tool that eliminates

breast cancer or that turns it from a disease that kills into one that is chronic but

can be controlled.

THE RANDOMIZED TRIALS

At the January 2002 PDQ Board meeting we considered an article authored by

Drs. Ole Olsen and Peter Gotzsche of the Nordic Cochrane Collaborative and that

appeared in The Lancet in October 2001. This article critiqued the randomized trials

that have been conducted to evaluate the benefits of screening mammography and

cited a number of deficiencies and flaws. Many of these were known previously and

there was little original information in the review. However, it served to put the

trials’ deficiencies into perspective and led us to re-evaluate the credibility of the

trials. We decided to revise our breast cancer screening statement and to refer to

the Olsen-Gotzsche article. The plan is to discuss and possibly finalize the revision

at our meeting in March. The current version of the statement indicates that the

estimates of the benefits of screening are uncertain. Therefore, in a sense the revision will be minor. However, we plan to indicate that the existence of benefit is

itself uncertain.

Olsen and Gotzsche reviewed the seven randomized trials. One was conducted in

Canada, one in New York, one in Edinburgh, Scotland and the other four in Sweden. The PDQ panel discounted some of the deficiencies pointed out by Olsen and

Gotzsche but we agreed with others. In the first category, most of us (1) felt that

their focus on all-cause mortality (rather than breast-cancer specific mortality) was

too strong, (2) that imbalances in randomization were not a major concern (except

in Edinburgh) and (3) regard the use of mammograms in the control groups (to coincide with the end of the screening period) of three of the Swedish trials to be a reasonable design strategy. From our perspective the trials had four types of major deficiencies. They applied to some but not all of the trials. The first three are potential

sources of bias favoring the screening group and in each case there is some evidence

of actual bias in the trials.

(1) Women with pre-existing breast cancer were preferentially excluded from the

screening group. The problem was most severe in the New York trial in which 853

women in the screened group and 336 in the control group were excluded because

they had breast cancer at the time of randomization. Excluding women with breast

cancer is not unreasonable, but the numbers excluded in the two groups would be

about the same had there been no bias. If these women had been included and only

9 percent of the differential of 517 women died of their disease, the breast cancer

mortality rate would have been higher in the screened group than in the control

group.

(2) Attribution of cause of death was made with knowledge of whether the woman

was in the screened group. Blinding assessment of cause of death to assigned intervention is fundamental in good clinical trial practice. For example, an assessor

might be more likely to attribute a death to lung cancer if the woman’s cancer was

detected through screening and to metastatic breast cancer if the woman had been

in the control group. There is evidence that this bias was real. The numbers of

deaths have changed in unusual ways from one report of the trial results to the

next: The number of breast cancer deaths in the control group always increases over

time but it sometimes decreases in the screened group.

(3) In three of the Swedish trials women in the control group were supposed to

have a mammogram, which was scheduled at the time of the last mammogram in

the screened group. Then, deaths due to breast cancer in the control group would

be counted only if they were diagnosed at or before this mammogram and in the

screened group if they were diagnosed at or before the last mammogram. This design is reasonable. But the scheduled control mammogram slipped in all three trials,

allowing for more time to detect cancers in the control group. The slippage was by

as much as 18 months. As a consequence, the control group in the Go ̈teborg trial

had 21% more breast cancers detected than did the screened group. Such an observation seems impossible (in an unbiased design) because mammography is very good

at finding breast cancers.

(4) No independent audit of trial results. Having an independent audit is a generally accepted in medical research and it is essential for a trial to be credible. For

example, the FDA routinely audits clinical trials that provide the basis for an experVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00051 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
48

imental drug’s safety and efficacy. None of the Swedish investigators have opened

their results to external inspection (but some have recently indicated their willingness to do so).

The Canadian trial was subject to none of these biases. It has been extensively

audited and its data are openly available for external examination. Both parts of

the Canadian trial (one admitted women in their 40s and the other admitted women

in their 50s) found a higher breast cancer mortality rate in the screened group, although the increase was not statistically significant. The other trials fell prey to one

or more of the biases, although it is not known whether there were biases in the

first part of the Malmo ̈ trial.

HOW CAN PEOPLE DIFFER SO IN THEIR EVALUATION OF EVIDENCE?

Physicians learn by experience. At least 90 percent of what is known in medicine

today is the result of clinical observation, with the remaining knowledge deriving

from randomized clinical trials. Experience is a great teacher. But when it comes

to inferring the benefits of screening, clinical observation is fundamentally subject

to flawed interpretation.

Women with breast cancer detected mammographically have extremely good prognoses in comparison with those having cancers detected in any other way.

Mammographically detected tumors are smaller and are less likely to have spread

to the axillary lymph nodes. Since women whose breast cancers were found by a

mammogram do so much better, there is a tendency to attribute the benefit to mammography. Unfortunately, this logic is wrong. The fallacious aspect is not simply a

nuance—it is a mistake that gives rise to profound misconceptions. And it is a logical lapse to which doctors and patients alike can fall prey.

Suppose temporarily that screening mammography has no survival benefit. Clinicians would still see precisely what they do see. Consider a 50-year-old woman who

has breast cancer and who is destined to die of her disease at age 60. However, she

does not yet know that she has breast cancer. It would be found on a mammogram

if she were to have one, and she would live for ten years with breast cancer. But

without a mammogram it would show up clinically only when its symptoms become

apparent, say at age 55. So without a mammogram she lives for only five years after

her cancer is discovered. The discrepancy between ten years and five years results

from what is called lead-time bias. It means that women whose cancers detected by

mammography live longer than do those detected otherwise, and this is true even

if screening has no true benefit.

There is another kind of bias—called length bias—that is even more important

in magnitude, but it is not as easy to understand. It is related to the fact that breast

cancer is a heterogeneous disease. Again, assume temporarily that screening has no

survival benefit. We understand some of the factors that give rise to this heterogeneity, but not all of them. Some cancers grow rapidly and others take a more indolent course. Suppose just for the sake of discussion that there are two kinds of cancers: half grow fast and the other half grow slowly. We cannot determine which is

which and so we treat them similarly. Suppose that after their cancer is detected

via mammography, patients having the first type live an average of five years and

patients with the second type live an average of 35 years (not counting causes of

death other than breast cancer). So the average survival for women whose cancers

are detected by mammograms is about 20 years. In the absence of mammography

the first type of cancer might show symptoms with only three more years to live

(a lead-time of two years). Some portion—say one half—of the women who harbor

the slowly growing tumors will die of other causes before it is discovered. The other

half of these women will discover them with 24 more years to live, say, a lead-time

of 11 years. There will be 25 percent fewer breast cancers in the non-mammography

group. Two-thirds will live an average of three years and one-third will live an average of about 24 years, for an overall average of ten years. So women diagnosed with

mammography live about ten years longer than those detected otherwise. This enormous difference is pure artifact since we assumed that screening had no benefit.

The above assumptions were simplified to make a point. No one thinks that there

are only two kinds of breast cancer. But everyone recognizes that the disease is heterogeneous. Length bias and lead-time bias are present regardless of the form of

heterogeneity. Together they account for enormous differences in apparent survival,

as measured from the date of diagnosis, between screened and unscreened cancer

patients. These differences are so large that they are detectable by physicians in

their everyday practices. No wonder physicians are persuaded of screening’s benefits. But the observed benefits may be completely spurious. In other words, apparent

survival from diagnosis may be longer, but life expectancy may not change at all.

Hence the need for randomized trials.

49

RELATIVE RISK VS. ABSOLUTE RISK

If there is a benefit of screening then the benefit is modest. To see this, ignore

the criticisms of the trials and take their results at face value. The benefits evinced

vary considerably from one trial to the next. Outside of the Canadian trial (which

showed no benefit), the highest quality results are from the Swedish trials. The

most recent results (out to 18 years) of the Swedish trials show a reduction in breast

cancer mortality of 21% (over all ages) in favor of screening. The value 21% is a

relative risk reduction, which is convenient as a statistical measure of benefit. But

relative risk is difficult to interpret clinically. One measure of absolute risk is to convert the 21% into expected life gained per woman screened. In the first 18 years

following initiation of screening in the Swedish trials the average gain is about 4

days. (In contrast, quitting smoking adds years to one’s expected lifetime.) Of

course, only those women who are eventually diagnosed with breast cancer share

in any benefit. Suppose 10% of the women get breast cancer eventually. Then each

woman with cancer gains an average of about 40 days. How this is apportioned

among the women diagnosed with cancer is not clear. From the trial results it is

impossible to distinguish whether (i) each breast cancer patient gains exactly 40

days, (ii) fewer than one percent of patients gain 18 years or more and the rest gain

nothing, or (iii) something between these two extremes. Put another way, it is not

possible to know whether a small proportion of lives are saved by screening or a

large number of women have their lives extended by a small amount, or some combination of the two.

WHAT SHOULD WE TELL WOMEN?

The short answer is ‘‘The truth.’’ The benefits of screening are uncertain and

women should be told this. They may be confused. Confusion is a legitimate state

of knowledge, one that may be appropriate in this case. It is a mistake and it is

patronizing to women to pretend that we know something we do not. Women have

a right to hear about the risks of screening and about the uncertainties regarding

the benefits of screening. They should hear all points of view and then decide for

themselves. Making this decision will not be easy for some women. We should provide them with decision aids that will inform them of what is known and help them

weigh the benefits and risks.

The risks of screening may seem minor but they are important nonetheless, and

they are common. From four percent to ten percent of women screened are found

to have an abnormal result. The ensuing recommendations range from a follow-up

mammogram to having a biopsy. Eighty to 95 percent of the abnormalities turn out

to be benign. Obviously, not having cancer is good news, but an estimated 28 million

women have mammograms each year, and so a million or more go through the anxious experience of an abnormal test until the final result is known. After ten mammograms the cumulative risk of a false positive result is about 50 percent and about

1 in 6 have biopsies that turn out to be negative. In addition, we know that screening misses about 15 to 25 percent of breast cancers.

Another potential consequence is overdiagnosis. Some breast cancers that may

never have progressed become symptomatic during a patient’s lifetime. We don’t

know which of these cancers will progress and so essentially all women with screening-detected breast cancer are treated surgically, with or without radiation. This

may result in unnecessary surgery for some women. Of course, even this serious

consequence may be acceptable if the test is saving the lives of other women.

A problem with setting guidelines such as those we have now is that it conveys

the message to physicians that screening is an imperative health measure. A woman

who decides that the risks outweigh the benefits should not be made to feel that

her decision is somehow irrational. A 58-year-old woman from New Jersey sent me

the following lament: ‘‘Sadly, in my experience anyway, I have found it impossible

to have a rational conversation with a physician, where my concerns are respected

on the topic of mammograms, as the NYTimes article says a patient should have.

Doctors get belligerent and almost hostile if I say I have reservations about getting

a yearly mammogram. The upshot is that I don’t feel I have a good relationship

with a physician, and that is not good. A good scientist is not afraid to express uncertainty on a topic or to discuss a topic openly. I’m afraid the practicing physicians

who I have come across do not have that scientific mind-set.’’

WHERE TO GO FROM HERE?

It is not possible to do another randomized trial, at least not in the United States.

Women want either to be screened regularly or not. Few would let a coin toss make

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their decision. However, there are developments that may help elucidate the issue,

and steps that we can take.

(1) Provide women with decision aids in which they are informed of the benefits

and risks, including uncertainties, and helped to weigh them in making a decision.

(2) Audit of the Swedish trials. A positive consequence of the PDQ’s position and

the ensuing discussion in the press was reported by John Crewdson in the Chicago

Tribune of January 31, 2002: Several of the Swedish investigators ‘‘announced last

week that they would release their detailed data, including patient files, to researchers at the U.S. National Cancer Institute or another international body.’’ (Hopefully,

the recently announced NCI guidelines will not lead to the Swedes withdrawing this

offer.) If an audit of these trials examines the biases and confirms the recently announced 21% reduction in breast cancer mortality then I for one will agree that

screening has a benefit.

(3) Cancer Intervention and Surveillance Network (CISNET). This is an NCIsponsored program that considers a variety of cancers. I am one of seven Principal

Investigators considering breast cancer. Breast cancer mortality in the United

States has decreased by nearly 15% over the last decade. This coincides with the

wide scale introduction of screening mammography. It also coincides with the dramatic upsurge in the use of tamoxifen and improvements in chemotherapy. We use

statistical modeling to conclude how much screening mammography, hormonal therapy and chemotherapy have contributed to this decrease. Of special interest is the

possibility of synergism between screening and treatment. For example, it may be

that treatment with tamoxifen and chemotherapy has more benefit when a tumor

is discovered by a mammogram at an earlier stage. We use annual data concerning

who got screened, who used tamoxifen, etc. An advantage of this approach is that

it applies to mammography actually used in practice in the late 1980s and into the

1990s, which may have been better than that used in the randomized trials. Another advantage is that we assess effectiveness in the context of actual clinical practice rather than in the possibly artificial world of clinical trials.

(4) The third development is the most promising of all. Our understanding of the

biology of breast cancer has increased greatly in recent years, but we still know relatively little. Breast cancer would not be fatal if it were to stay in the breast. Its

lethality stems from its penchant for traveling to and setting up shop in other places

in the body, such as in bone, the lungs, liver and brain. The question is, When does

it do these things? Perhaps cancers manifest their metastatic potential (or not)

when they are tiny, say when they total only a million or so cells. If so then they

will have dispatched their malevolent messengers from the breast to the rest of the

body before even the best mammography can detect their presence. Or it may be

that they start sloughing off tumor cells only when they become large enough to

have been detected and removed. We know little about such matters. And we know

little about the relationship between the biological characteristics of tumors and

how to treat them. These issues are being addressed by researchers around the

world. Research progress will help us better understand the relationships between

biological markers, early detection and treatment. Especially exciting are the

genomics and bioinformatics revolutions. These are in their infancies and are well

funded, but they deserve all the attention they have received.

Thank you for the opportunity to discuss this extremely important issue in women’s health, a topic to which I have and will continue to dedicate my career. I would

be happy to answer questions or provide further details.

Senator MIKULSKI. Dr. Eyre?

Dr. EYRE. Good afternoon, Madam Chairwoman and distinguished members.

As chief medical officer at the American Cancer Society, I am

honored to be here today and want to thank you for the opportunity to testify about the strong science supporting the value of

mammography in saving lives.

The American Cancer Society is the largest community-based

health organization dedicated to preventing cancer, saving lives

from cancer, and diminishing suffering from cancer.

We have established very ambitious goals for the year 2015 to reduce the incidence and death rates of cancer as well as improve the

quality of life of cancer patients. In order to do that, cancer prevention and early detection is a critical aspect of this strategy.

51

You have heard from Dr. von Eschenbach about the magnitude

of the breast cancer problem, but one fact he did not give you

which I think is astounding is that a woman who dies of breast

cancer in America loses 19 years of life due to premature death, as

judged by average life expectancy. As a medical oncologist and cancer specialist, I have personally taken care of over 1,000 patients

with breast cancer and witnessed the suffering that occurs to patients and their families from breast cancer, and I believe that we

are making vast progress in this country, saving thousands of lives

from breast cancer, and I hope to not see that reversed.

We too would add our encouragement behind the U.S. Preventive

Services Task Force’s recent affirmation of mammography and believe that it adds to the scientific evidence behind it. The scientific

evidence supporting mammography in reducing breast cancer death

rates is solid, and I would like to share just a few comments about

the Society’s position on this.

Over 100 years ago, it was hypothesized by a French physician

that breast cancer began as a single focus, gradually began to

spread, went through the lymphatic channels into the vascular

channels, resulting in the death of the person. This concept has

been verified and gives rise to the notion that if you can find it

early enough, surgical removal of the cancer results in cure.

It was not until the 1950’s, however, that we began to find mammography able to detect early breast cancer, and this gave rise in

the 1960’s, actually, to the HIP study in New York City which was

the first large-scale randomized trial, with 62,000 women randomized to mammography and clinical breast exam versus usual care.

The result of that study after follow-up was a 30 percent reduction

in death rate in breast cancers in the study group compared to the

control group.

Before moving on, I would like to discuss with a little bit of evidence the data on size and stage of cancer. If you find early disease—no lymph node involvement, no disseminated disease—5-year

survival of breast cancer in America is 97 percent. In contrast, if

you find breast cancer when it has already demonstrated spread,

79 percent of those women will die in that first 5 years. Our goal

is survival, and the scientific evidence has repeatedly demonstrated

that screening can help achieve this goal.

Following the HIP study, the American Cancer Society and the

National Cancer Institute launched a major nationwide demonstration project, the BCDDP, in which at 10 centers, 280,000 women

were screened from 1973 to 1980, and comparing the results of

those individuals to the results of the population revealed a substantial reduction in mortality.

Subsequent to those trials, there have been studies in Great Britain, in Sweden, and in Canada. Almost all of those studies except

the Canadian studies have demonstrated a statistically significant

reduction in mortality. The Cochrane group, as you know, has recently criticized these studies. We find their analysis flawed. We do

not agree with the fact that those studies had substantial imbalances within them, and in fact the Cornell group pointed out in the

Malmo study that Senator Harkin referred to that if you had just

followed the people longer, there was a significant reduction in

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mortality, and the Cochrane group did not even acknowledge that

second report.

We believe that mammography is not a perfect test; it has flaws.

It is an interim effort to help control breast cancer, and as we

progress—and we applaud Dr. von Eschenbach’s scientific studies,

and we are funding scientific studies into finding answers as to

how to present cancer, how to block it from occurring, and if it occurs, how to cure it—it will only be then that we will get the final

control. But in the meantime, mammography is of value in reducing the death rate from breast cancer, and the American Cancer

Society applauds and continues to support this effort with information to patients, to women, and with the recommendation that

women 40 and over should have annual mammograms.

Thank you.

[The prepared statement of Dr. Eyre follows:]

PREPARED STATEMENT OF HARMON J. EYRE, M.D.

Good afternoon, Madam Chairwoman, Mr. Chairman, Senator Frist, Senator

Specter, and distinguished members of both Committees. I am Dr. Harmon Eyre,

Chief Medical Officer and National Vice President for Research and Medical Affairs

of the American Cancer Society. I am honored to be here today, and I want to thank

you on behalf of the more that 28 million volunteers and supporters of the Society

for the opportunity to testify about the strong scientific evidence supporting the

value of mammography in saving lives from breast cancer. The American Cancer Society commends you for conducting this very timely and important hearing.

I respectfully asked that my comments be submitted for the record.

The American Cancer Society is the largest nationwide community-based voluntary health organization dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives and diminishing suffering from cancer

through research, education, advocacy and service. We have set ambitious goals for

the year 2015 to reduce the number of people dying from and being diagnosed with

breast and other types of cancer, and to significantly improve the quality of life for

all cancer patients, survivors, and their families. While we believe that national

achievement of these goals is possible, increased awareness and utilization of cancer

prevention and early detection tools is critical to our success.

Madam Chairwoman and Mr. Chairman, before setting out to explain the American Cancer Society’s view on the benefits of mammography, I would like to take

a moment to call attention to the terrible impact that breast cancer is having on

women in this country. This year, 203,500 new invasive cases of breast cancer will

be diagnosed, and an estimated 40,000 women will die of the disease. On average,

a woman dying of breast cancer loses approximately 19 years of life she might otherwise have had. The human face on those statistics translates into families watching

a loved one struggle with advanced, unsuccessfully treated disease, and a family

and community that ultimately are left to mourn her loss. As a physician and medical oncologist, I have treated thousands of breast cancer patients in my career and

observed first hand the heartbreak this disease visits on families and loved ones.

Over the years, I have also witnessed the progress we have made, so that fewer

women are dying from breast cancer. I do not wish to see our country lose the

ground we have gained.

To this end, we are hopeful that the recent announcement of the U.S. Preventive

Services Task Force’s update of their breast cancer screening guidelines and their

endorsement of mammography for women ages 40–69, will add to the weight of the

wide-scale rejection of the recent mistaken notion that mammography is valueless.

Madam Chairwoman, Mr. Chairman, and members of both committees, the scientific evidence supporting the value of mammography in effectively reducing

deaths from breast cancer is solid, and I appreciate having the opportunity today

to share with you the Society’s view on this important subject.

THE ORIGINS OF EARLY DETECTION IN BREAST CANCER

The importance of detecting localized breast cancer is well established. It was first

recognized in the mid-18th century by a French physician who proposed that breast

cancer originated as a localized disease that subsequently spread through lymphatic

channels to the general circulation. This key concept established the idea that surVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00056 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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gery, if performed early, offered the potential to cure breast cancer. Effective means

of early detection eluded us, however, until the early 20th century when it was first

demonstrated that breast disease could be detected with x-rays, allowing for diagnosis of breast cancer even before symptoms, such as lumps, could be detected by

a woman or her physician.

As you well know, the path toward turning a promising idea into a practical solution can be a time consuming journey in the scientific world, because of the high

standards of scientific evidence that are required. Promising work in breast imaging

continued through the first half of the 20th century, eventually leading to a turning

point in the early 1960s when Dr. Philp Strax, a radiologist in one of the Health

Insurance Plan of Greater New York medical groups, proposed a large-scale study

to evaluate the potential of mammography and clinical breast examination to reduce

deaths from breast cancer. Professor Sam Shapiro, Director of Research and Statistics at the Health Insurance Plan, and Dr. Louis Venet, a surgeon with experience

in clinical breast examination screening programs, later joined him as co-investigators. This study became the Health Insurance Plan of Greater New York Project,

historically known as the HIP Study, and was initiated in December 1963. It was

the first randomized, controlled trial to evaluate the efficacy of breast cancer screening with clinical breast examination (CBE) and mammography. Approximately

62,000 women aged 40–64 were randomly assigned to two groups: the study group

was offered annual clinical breast examination and two-view mammography for four

years, and the control group received usual care.

The fact that this study was a randomized controlled trial is important because,

with respect to cancer screening, it is critical to know whether the actual act of

screening is the factor making the difference in saving women’s lives. The ideal

study would be one in which you had two identical groups of people, with the only

difference between them being whether they were screened. Obviously, a study like

that is impossible. Therefore, the next best thing is to randomly assign a large

group of individuals to either the group that is offered screening or the group that

receives usual care. If our randomization has succeeded, and the study is well organized to maintain the integrity of equality between the study group and the control

group, then we come very close to the theoretical ideal of two identical groups. Randomization of the women in the study controls for factors we know about and factors

we don’t know about that could bias our findings. It helps us demonstrate whether

or not screening, and not some other factor, is the reason death rates are reduced.

The HIP study was a dramatic turning point. It offered hope for the first time

that through intervention we could reduce the number of women who died from

breast cancer. The randomized HIP study demonstrated that there were approximately 30% fewer breast cancer deaths in the study group compared with the control group. Without question, the results of the HIP study ushered in a new era in

breast cancer control, one in which there would be increasing emphasis on detecting

and treating breast cancer before the onset of symptoms. However, scientists are

rarely willing to recommend wholesale change in health policy based on one study.

THE LOGIC BEHIND EARLY DETECTION

Before I talk about the next series of studies, I want to quickly discuss the logic

behind early detection and the relationship to the underlying biology of breast cancer. Breast cancer is a progressive and systemic disease, in which our ability to treat

and cure a small tumor is much greater than our ability to treat and cure a larger

tumor. Treatment is easier and the outcomes are better, when the cancer is caught

before there is lymph node involvement and before the cancer has metastasized, or

spread, to distant organs. There is no more consistent and straightforward measure

of a breast cancer patient’s prognosis than the size of the tumor. A few statistics

to put this in perspective: When breast cancer is still localized—meaning that it has

not spread to other organs—97 percent of patients survive for five years or more.

Once the disease has spread to other organs, however, prognosis is bleak, with 79

percent of patients dying within five years. Our goal is survival—and scientific evidence demonstrates that screening can help us achieve the goal of lives saved. Indeed, the important role screening plays in reducing breast cancer deaths has been

demonstrated repeatedly.

PROMISING CONCEPT TO PROMISING SOLUTION: THE IMPORTANCE OF ROUTINE BREAST

CANCER SCREENING

As I mentioned, the HIP study was not enough on its own to recommend screening to the general population. Before recommending screening to the general population, we would have to not only know that screening works, but that it was possible to implement an effective screening program in the community. The results of

54

the landmark HIP study led the American Cancer Society and the National Cancer

Institute to collaborate on a larger project to determine the practicality of bringing

mammography screening to women at the community level. This project, known as

the Breast Cancer Detection Demonstration Project, or BCDDP, screened over

280,000 women at 29 centers between 1973 and 1980. Participation rates were high

over the course of the study and final analysis underscored the importance of mammography screening—nearly half of all breast cancers in this study were found by

mammography alone.

Furthermore, among study participants, breast cancers were diagnosed at more

favorable, early stages when compared with breast cancer cases among women nationwide during the same period. Most importantly, overall long-term survival has

been much better among participants in the screening study. The bottom line is

that, based on these two studies, we now had enough scientific evidence to say that

mammography was an effective tool to detect breast cancer early, and breast cancer

deaths would be reduced if we detected the disease before it had spread. Mammography was a tool that could make a difference.

Thanks to the groundbreaking results of the BCDDP and the HIP study, the Society determined that there was sufficient evidence to promote routine breast cancer

screening in the U.S. as a public health initiative in 1980. As the largest national

health organization devoted to reducing cancer incidence and deaths, the American

Cancer Society is well recognized as a primary resource for cancer screening guidelines. Our screening guidelines are established through a rigorous scientific review

process and are re-evaluated at least every five years. We have reviewed the scientific evidence relating to mammography repeatedly since 1980, and we have continuously concluded that while improvements in technology are certainly welcome,

mammography remains the best tool we currently have to detect breast cancer

early. In fact, as the Institute of Medicine recently concluded, mammography presently is the gold standard by which breast cancer is detected early.

As I mentioned, evaluation of mammography has continued. Between 1976 and

1982, six additional randomized controlled trials were initiated in Edinburgh, Sweden, and in Canada. While there are differences in the results, all of these studies

(with the exception of the Canadian studies) show a benefit from breast cancer

screening with mammography, both with and without clinical breast examination.

In fact, the trials show a statistically significant reduction in breast cancer death

by about 25–30 percent for women aged 40 and older and similar benefits for women

in their forties compared with women aged 50 and older.

The accumulation of evidence from randomized trials over the years has strengthened the science behind breast cancer screening. In fact, one remarkable observation

from the trials is that in the group offered screening, the observed reductions in the

mortality rate in each trial are consistent with reductions in the rate of advanced

breast cancer when compared with the control group. Put simply, the studies

showed that detecting breast cancers early increases the chances of survival.

It is important to note that trial results derive from controlled environments. It

is also necessary to demonstrate whether true benefits are being achieved under

real-life circumstances. In Sweden where screening is a national health priority,

those women receiving regular screening have been shown to reduce their risk of

dying from breast cancer by over 40 percent compared with women who do not get

regular screening—a fact that should not be ignored.

REVISITING COMPLEX QUESTIONS: REPORTS FROM CORNELL UNIVERSITY AND COCHRANE

Madam Chairwoman and Mr. Chairman, as you know, in spite of the overwhelming evidence, mammography has not been without its detractors. Recently, two of

these detractors have been able to gain widespread media attention and cause great

confusion among the public about the value of mammography. I am speaking of

course about the Cochrane Review on Screening for Breast Cancer as published in

the Lancet. In my view, this current confusion is a regrettable development that is

harmful to women. Given the weight of evidence from the trials and the reductions

in breast cancer death rates observed in real life instances, the conclusions of the

Cochrane Review are quite frustrating to many in the scientific community. Indeed,

the Cochrane conclusions are at odds with the most fundamental understanding of

breast cancer as a progressive disease. Moreover, these conclusions run contrary to

decades of supporting scientific evidence from the individual trials, meta-analyses,

observational studies and case series, national trends, and confirmatory, independent expert reviews conducted by medical and scientific groups in North American

and Europe.

As you are probably aware, the Cochrane report rejected five of the seven major

mammography trials as flawed. The researchers then claimed that the two remainVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00058 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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ing trials showed that mammography was not beneficial. Inexplicably, one of the reports they selected was an early report of the Malmo study. The early report was

made before there had been sufficient time for follow up and therefore did not show

a difference in breast cancer deaths between the study group and control group

when all deaths in each group were compared. For some unknown reason, the

Cochrane review ignored a second later report of this study that had allowed sufficient time for follow up. This later report did indeed show that mammography was

beneficial. In fact, it showed that there were 19% fewer deaths in the group offered

screening.

Because most breast cancer deaths do not occur rapidly after diagnosis, experts

in the evaluation of screening have known for years that a lengthy period of follow

up in a screening study is necessary to observe a lower mortality rate if there is

one. In fact, this very point was strongly made in a report in the Lancet only a few

weeks ago by investigators from Cornell University. The Cornell investigators demonstrated that once a sufficient amount of follow up was allowed, even the first

Malmo study shows a clear reduction in breast cancer deaths. In other words, the

Cochrane analysis used incomplete data, making their conclusions suspect.

Knowing that the results of a scientific study can have a great impact on many

aspects of health care and health policy, standards for conducting these types of

studies are set high and are adhered to by most of the scientific community. Unfortunately, on close examination, it is evident that the Cochrane review does not adhere to some of these standards and is deeply flawed. Indeed, it appears that the

review’s investigators failed to perform a careful examination of the published literature—for example, missing the second Malmo report—and made arbitrary and

inconsistent judgments about study quality. Moreover, the Cochrane analysis concluded that the only reliable endpoint for comparison was not death from breast

cancer, but death from all causes.

Using death from all causes as the means for evaluating mammography effectiveness is far-fetched in the extreme. The trials were designed to demonstrate a difference in breast cancer deaths—not deaths from all causes. To demonstrate a difference in deaths from all causes, an enormous number of people would need to be

enrolled in any trial. These trials were too small to individually demonstrate a difference in all cause mortality and were never intended to do so. Moreover, breast

cancer screening cannot logically be expected to reduce deaths from hip fractures,

diabetes, trauma, or other causes of death.

Furthermore, the Cochrane analysis alleges that some of the trials should be ignored because of possible bias and error in determining the cause of death. This assertion is simply wrong, since the level of error, due to dishonesty or incompetence

on the part of blinded and non-blinded expert panels, would have had to be entirely

habitual to change the results so completely. All told, the claims made by the

Cochrane review are based more on conjecture than an actual demonstration of errors.

The authors of the Cochrane analysis are part of a group in the scientific community who hold that studies should look only at all-cause mortality, not on mortality

from breast cancer alone. This train of thought is quite misleading, because the goal

of any preventive health program is not to prevent death, which will occur eventually, but to reduce our chances of dying prematurely Breast cancer screening makes

sense for women between the ages of 40 and 70 because breast cancer is a leading

cause of death in that age group—it offers women the chance to save those 19 years

of life that I mentioned at the beginning of my remarks.

This raises another point. Screening is an undertaking in which we test the many

to find the few. No screening test is 100 percent accurate. In some cases, cancer will

be missed during screening. In other cases, women will be told they need additional

tests for abnormalities that ultimately turn out not be cancer. Providers must handle each step of the screening process with great sensitivity. Likewise, more education can be done to assure women that ‘‘false positives’’ are part of the pathway

to a normal interpretation. A group of investigators at Dartmouth found that women

are highly accepting of false positives as part of the process of saving lives from

breast cancer. This does not mean we should not devote more attention to reducing

the avoidable false positive rate, but it is important to note that many women understand the inevitability of false positives and accept them as part of the process

of early detection.

Another criticism of mammography is that it detects ductal carcinoma in situ, or

DCIS, a non-invasive cancer. In the course of screening for invasive breast cancer,

we will detect DCIS. Since not all DCIS will progress to invasive disease, screening

has been criticized for over treating DCIS.

Madam Chairwoman and Mr. Chairman, approximately a third of DCIS may

progress to invasive disease and we do not know which will or will not progress.

56

The notion that detection of DCIS should be avoided, or that screening should be

postponed until DCIS progresses to invasive disease betrays a fundamental misunderstanding about the biology of breast cancer and the interplay between disease

progression and early detection. The intent of breast cancer screening is the detection of small invasive cancers in order to give women an advantage in fighting their

disease. The challenge today and in the future is tailoring the treatment of DCIS

to ensure that it is treated appropriately and that a woman is not put through a

greater treatment ordeal than is necessary—but that’s a treatment issue not a

screening issue. The only option for avoiding the diagnosis of DCIS is not being

screened for breast cancer, which would make no sense at all since the incidence

rate of invasive breast cancer is many times greater than the chance of a diagnosis

of DCIS.

All told, in addition to numerous critiques of the Cochrane Review in published

literature by well-known experts on screening, no national or professional body has

found that this review’s conclusions are convincing. As additional reviews are published, and as additional national groups reject the review’s flawed interpretation

of the data, it is our hope that policymakers and others will devote more attention

toward setting the record straight. Mammography, while not a perfect tool, is currently the best tool we have to catch breast cancer early and to reduce deaths from

the disease.

NEXT STEPS

Madam Chairwoman, Mr. Chairman, and members of the Committee, we have

made incredible progress towards reducing deaths from breast cancer in North

America and Europe. Here in the U.S., after nearly two decades of a public-private

partnership in health promotion, a majority of women aged 40 and older are receiving mammograms. The efforts to improve the quality of mammography, and in particular the importance of the landmark Mammography Quality Standards Act of

1992, which the Chairwoman authored, have assured every woman in this country

of higher quality breast imaging. These efforts have produced results. The death

rate from breast cancer has declined by over 20% in the last decade. According to

the American Cancer Society, progress in the U.S. in breast cancer screening, improved therapy, and increased awareness means that there will be many thousands

fewer women who will be expected to die this year from breast cancer than would

have died if mortality rates were the same today as they were in 1989. Furthermore, new technology, such as digital mammography, computer-aided detection, and

potentially MRI hold the promise for even more successful breast imaging technology—but at this time, mammography is the best tool we have.

The American Cancer Society will continue to provide information designed to inform women of the benefits and limitations of mammography screening. We are confident that, armed with information, women and their health care providers will

continue to see mammography as the best current strategy to reduce death from

this disease, and that those whose confidence was shaken by the recent media attention will regain their confidence as the authoritative and credible interpretation

of the scientific data on mammography prevails. To this end, we urge women 40 and

older to continue to follow the advice of their physician and be screened for breast

cancer annually.

Madam Chairwoman, Mr. Chairman, and members of the Committee, thank you

again for the opportunity to speak to you today.

Senator MIKULSKI. Senator Harkin, you chair the appropriations

committee on the other part of this joint hearing, so why don’t you

kick off the questioning of this panel?

Senator HARKIN. Thank you very much, Madam Chair.

Dr. Berry, again, in layman’s terms, let me try to propound this

question. All things being equal, if a woman has the opportunity

to have mammogram screening available to her after age 40—and

she can obviously do a self-exam and have a physical every year—

would it be your advice to her to skip the mammogram, assuming

she can afford it, it is available and so on? Would you say just skip

it, or would you advise her to have a mammogram as part of the

toolbox that we talked about earlier of different things that we can

do to try to detect breast cancer?

57

Mr. BERRY. I would not advise either way. I would discuss with

the woman—as, for example, I have with my wife and daughters—

what the benefits are, what the uncertainties are associated with

those benefits, what the risks are—and the risks may be more important for one woman than for another women—and if that

woman, including members of my family, decided to have a mammogram, I would support that to the utmost; if they decide not to,

I would support that as well.

Senator HARKIN. Is it true—or, is it factual—that the earlier

breast cancer is discovered, the higher the possibility will be—or

probability will be—that a woman could successfully have that

treated one way or the other—through surgical removal or whatever—and have a longer life span and a healthier quality of life

than if that woman waited until the cancer had grown and

metasticized?

Is that a factual statement or not? Do you want me to repeat it?

Mr. BERRY. No, no. I think I understand the question. If a

woman has cancer—if somebody says to you, ‘‘I have cancer,’’ and

it was detected mammographically, that woman has incredibly

good prognosis. If it is not detected mammographically she has

poor prognosis. That does not mean that the mammogram did it.

As Dr. von Eschenbach indicated, there are tumors that are relatively indolent that are found with mammogram that may not

ever be found in the course of the woman’s life. Autopsy studies

have shown in the United Kingdom that women have as much as

35 percent invasive disease that never affected their health.

There is a lead time bias. There is a lead time associated with

mammography that if you find it earlier—it is a very compelling

notion—if you find it earlier, you may be able to treat it better.

Does it really turn into a benefit? That is what the randomized

trials are about. But there is a lead time bias. If you look at a

woman, and you find the woman let us say 5 years earlier, that

woman is going to live 5 years longer after you have found the disease. That is one of the two biases I talked about in my report.

Senator HARKIN. In your statement, you say that ‘‘Women with

breast cancer detected mammographically have extremely good

prognosis in comparison with those having cancer detected any

other way. Mammographically detected tumors are smaller and are

less likely to have spread to the auxiliary lymph nodes.’’

Let me put it this way: I had a telephone conversation yesterday

with some breast cancer survivors in Iowa, and one woman said

about false indications, ‘‘Well, I would rather have a false positive

than a false negative.’’

Mr. BERRY. Obviously.

Senator HARKIN. Obviously. So I do not know that there is any

way to detect at an early stage whether a cancer is indolent or aggressive.

Mr. BERRY. So far not.

Senator HARKIN. So far not. Therefore, it would seem to me logical that if a woman could find a cancer earlier, not knowing

whether it is indolent or aggressive, and it could be removed with

the least invasive procedure, it would seem to me she would be far

ahead, rather than waiting until later on.

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Mr. BERRY. If you could find the first cell that mutated, there is

no question. The issue is when between that time—and it becomes

detectable by our current mammography—when between that time

does it have a metastatic potential—and there, we do not know. It

may already be doing its dastardly deeds when it is only a few million cells, when it cannot be detected mammographically.

Senator HARKIN. I do not know how to respond to that. It would

still seem to me, again as a layman, that the earlier you can detect

a cancer, the better your prognosis is going to be.

Mr. BERRY. There is no question about that. The question is does

it translate into a benefit for mortality. There are examples—for

example, the neuroblastoma issue, where we detected lots of cancer

really early, and we found out that it did not convert into a mortality reduction.

Senator HARKIN. I guess we are playing some kind of a word

game here. I do not like to put it in those terms, but it just seems

to me, again, that if I have breast cancer, I know that if I wait it

is going to metasticize at some point.

Mr. BERRY. Not necessarily.

Senator HARKIN. More often than not?

Mr. BERRY. No, no—well, actually, it depends on whether it is

detected mammographically or otherwise. If it is detected

mammographically, fewer than 50 percent will ever metasticize. If

it is detected otherwise, something possibly greater than 50 percent.

Senator HARKIN. Well, if it is detected mammographically, and

fewer than 50 percent metasticize, that is because something has

been done, right? I mean, you do not just detect it with mammography and say, okay, we are not going to do anything. Something

has to be done.

Mr. BERRY. Yes, but the question, Senator Harkin, is what has

been done. Several things have been done. One is that you have

found more cancer, and some of the cancer that you have found

may be incredibly important to find. I am not saying that mammography is not good. It may be incredibly important to find. But

some of what you find is not important to have found. The problem

is, of course, that we cannot distinguish which.

Senator HARKIN. Okay. I know what you are saying you would

say to women. You would tell them all the odds and let them make

up their own mind.

Mr. BERRY. Yes.

Senator HARKIN. But we are lay people, you know; we are not

scientists. We want to know odds-on what is the best thing to do.

We look to the medical community for this kind of advice and guidance and direction. And what I am hearing from most of the medical people I spoke to yesterday is that, as I said in my opening

statement, mammography is not the sole thing, but in combination

with other things it is a useful tool for early detection. And the earlier you detect it, the better your prognosis is going to be.

Mr. BERRY. If a woman says, ‘‘OK, you have told me all this stuff

and it does not make any sense to me. Just tell me whether to get

a mammogram,’’ and she says it to a doctor who has her best interest at heart, and the doctor says, ‘‘I think you should get a mammogram,’’ and she does, that is fine. I very much encourage that.

59

But I want that woman to be exposed to—if she wants—all the information that she can digest.

Senator HARKIN. Thank you very much. My time is up.

Thank you, Madam Chair.

Senator MIKULSKI. Thank you. I think that was a very important

exchange.

Senator/Dr. Frist?

Senator FRIST. Thank you both for your excellent presentations.

Dr. Berry, do you counsel patients at all?

Mr. BERRY. No, I do not.

Senator FRIST. Your training is a Ph.D. in biostatistics.

Mr. BERRY. That is correct.

Senator FRIST. You are being asked questions, really, that center

on the doctor-patient relationship, and you are answering from statistical data and your analysis of those statistics.

Mr. BERRY. That is why I put it in terms of my family. My family

listens to me—although not always.

Senator FRIST. I think that just for the audience, it is very important. If you hear a biostatistician looking at statistics and looking at the lead time bias and your explanation, which is very clear

in your presentation and in your writing—I think we need to be

very careful in posing hypothetical questions to you. If you just listen, you might say, here is a clinician who says he does not really—in terms of counseling patients regarding who should get a

mammogram or not—and really, you should not be in that position

to provide clinical advice to a particular patient. That is really

what you are saying.

Mr. BERRY. That is correct. That is absolutely correct.

Senator FRIST. With that, if someone comes to a clinician and the

clinician calls you on the phone, you will basically tell the clinician

what you have written here. Once again, you are not going to say

whether that patient should get a mammogram or not. Based on

the data out there, would you ever feel comfortable being in a position of answering whether someone should get a mammogram— again, recognizing that you are not a clinician—as a patient or a

woman who comes to you, or a husband, to the question of ‘‘Should

I or my wife get a mammogram?’’ Are you comfortable advising

them or counseling them at all, even given what you know?

Mr. BERRY. If somebody were to come to me and say, ‘‘I am putting myself in your hands; you are to decide whether I get a mammogram,’’ I would run away.

Senator FRIST. I think that is right. I think that is the correct

answer. But it is a position that physicians are in, because they are

looking at the biostatistical data. It is clearly confusing to the

American people and people around the world where the statistics

are limited and do not give the full answer. In your written statement, you do say that ‘‘When it comes to inferring the benefits of

screening, clinical observation is fundamentally subject to flawed

interpretation.’’ The implication of that to me is that one should

not rely on clinical observation.

Mr. BERRY. In the context of screening. It is very important in

the context of treatment. A doctor gives Mrs. Smith a treatment,

and Mrs. Smith does well. He or she learns from that, and that is

very important. What I am saying is you cannot learn in screening.

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Senator FRIST. And the biostatistician through screening looks at

large populations, which I think is potentially dangerous—inferring

how you should treat a particular patient. That is the implication

in your written testimony, and to me it is very dangerous as a physician to make that inference.

Could you just comment, because people are listening to your interpretation of biostatistics, and they are taking down what you

should advise the individual woman. I think that is dangerous as

a clinician. So I just want to ask for your response to help me understand that. And I think that is what Senator Harkin is struggling with as well. In his hypothetical question, you answered it

appropriately, but I do not think it leaves the correct image of what

we really want to answer, and that is an individual woman coming

in asking should she get a mammogram or not.

Mr. BERRY. I think there is a distinction between talking about

the individual as an abstract and the individual as a particular

one.

Senator FRIST. Yes, I agree.

Mr. BERRY. The individual as a particular one, I completely

agree. The individual as an abstract, I am interested in communicating with particular women, with women as individuals. These

are not policy statements that I am interested in. Other members

of the PDQ may differ from that. I am interested in a particular

woman’s decisions and what kinds of things she should consider.

When it comes to an individual, Jane Smith, that is a whole different story.

Senator FRIST. I think that is really important for us to understand in the hearings. The advocates, I think, will really be talking

about individuals. But as we look at biostatistics, it is confusing to

me as a clinician because I am in the business of looking at, whether it is transplantation or large populations, what to infer down to

the patient. When I read what you said, ‘‘But when it comes to inferring the benefits of screening’’—which, again, you qualified—

‘‘clinical observation is fundamentally flawed or subject to flawed

interpretation’’—it is screening that is right. I did not pick it up,

either; that is the benefit of mass screening. But when it comes to

an individual patient, which is what both patients want and what

physicians want, clinical observation may not be flawed because it

really does very much determine what goes on with that particular

patient, as you said, in that situation.

I do not want to belabor this, but again for the broad audience

here, I think we have to be very careful in taking biostatistics and

saying that basically, the observations which are applied to screening in a statement on policy of screening may not apply when it

comes to the individual patient. Correct me if I am wrong.

Mr. BERRY. I agree.

Senator FRIST. OK. I will stop there.

Senator MIKULSKI. Are you sure?

Senator FRIST. Yes. Thank you.

Senator MIKULSKI. First of all, Dr. Berry, I want to thank you

for being here. And know that the rigor of the questions in no way

challenges you and your dedication to trying to provide for women

from your perspective the best information they need. So please

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know that the rigorous exchange is in no way challenging your

commitment.

Mr. BERRY. Thank you very much I appreciate that.

Senator MIKULSKI. I just want that on the record, and I think we

would all concur with that.

In time, I might come back to you, but I want to turn to the

American Cancer Society and Dr. Eyre. I want to be clear on your

testimony. Could you repeat what are the guidelines of the American Cancer Society for women to have or not have guidelines?

What are the American Cancer Society’s recommendations and the

rationale behind them?

Dr. EYRE. Senator, thank you for the question. Far and away the

most important guideline for breast cancer is that women age 40

and older who are at average risk should have an annual mammogram combined with a clinical breast exam by their doctor.

We also advocate for teaching breast self-examination beginning

at age 20, and for women between ages 20 and 40, they should

have a clinical breast exam by their doctor at least every 3 years.

Those are our screening guidelines for breast cancer. We also advocate cancer prevention guidelines that speak to some of the

points that Dr. von Eschenbach talked about. They are nutrition,

physical activity, and modest consumption of alcohol at most if a

person drinks, in order to do what we know how to do to diminish

a woman’s risk.

We do have additional information about women at high risk, but

that does not apply across the board.

Senator MIKULSKI. When you say ‘‘average risk,’’ what does that

mean. For the women and the men who love them watching this

on TV or hearing reports on this, what would be an ‘‘average risk’’ as they are calculating what they should be discussing with their

physicians?

Dr. EYRE. The average risk accounts for 70 to 80 percent of

women in America. What we define as ‘‘high risk’’ are those individuals with first degree relatives with breast cancer, or those

women who have had a breast abnormality such as atypical ductile

hyperplasia on previous exams or biopsies, so that they fall into a

high-risk group or the extremely high-risk group, those who have

a genetic predisposition with the BRCA-1 or BRCA-2 gene.

So we are talking about average risk individuals as those women

who do not fall into those high-risk categories.

Senator MIKULSKI. Dr. Eyre, prior to this hearing, some things

were brought to my attention, and I do not have the data, but it

goes to women on birth control and also women who have sought

hormone replacement therapy.

You have spoken very clearly, thank you, on where there is a genetic predisposition. But information was brought to my attention

that women either on the pill, and now particularly women who

are taking hormone replacement therapy seem to have escalating

breast cancer when there has been no genetic propensity and so on.

Could you comment on what you have heard and also what your

comments might be on these issues related to hormone replacement

therapy, in terms of the average risk and should I be getting a

mammogram—particularly those young women who might be on

the pill, women who are ‘‘going through the change.’’

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Dr. EYRE. The American Cancer Society has followed 1.2 million

Americans by using our volunteers to enroll these individual, and

we now have 16-year follow-up data; half are women, and half are

men. We have looked very, very carefully at the risk factors associated with breast cancer in women, including the two that you just

mentioned, that is, birth control pills and hormone replacement

therapy. With both prolonged use of oral contraceptives or prolonged use of hormone replacement therapy, the risk of developing

breast cancer does increase over time. However, when you actually

look at the fatality rates, those women do not have a higher death

rate. There could be multiple answers for that. They may be being

seen by their doctors more often, being examined, getting mammograms, or they could be having a cancer develop that is a less aggressive cancer, so that the actual death rate for women in those

categories is nearly the same as those who do not take those hormones, either birth control pills or hormone replacement therapy.

Senator MIKULSKI. Would you encourage—and ‘‘you’’ meaning

again the American Cancer Society—those women who are either

on the pill or who have hormone replacement therapy to get annual

or close to annual mammograms because of this emerging set of information?

Dr. EYRE. The American Cancer Society very clearly recommends

that women discuss with their doctors all of their risk factors,

being age, sexual status in terms of reproductive status and use of

hormones, either as birth control pills or as hormone replacement

therapy, their exercise level, their weight, etc, and together, all of

those factors should be taken into account in determining health

behavior, and one of those health behaviors is screening.

We think that that adds to the impetus for a woman to have an

annual mammogram and an annual clinical breast exam.

Senator MIKULSKI. Thank you very much, Doctor. I think we

could go through another whole line of questions particularly where

a young women might start birth control at age 20, and would have

20 years of use of the pill by the time she hit 40. That, by my definition and I presume by yours, would be prolonged use and I think

would raise this.

I am now going to turn to Senator Clinton for any questions she

might have.

Senator CLINTON. Thank you, Madam Chairman.

I especially want to thank my colleagues, Senator Harkin and

Senator Frist, for their very informative lines of questioning. I just

have a few specific follow-up questions.

Dr. Berry, in your written testimony, you have a reference to the

audit of the Swedish trials, and you have a parenthetical statement

that, ‘‘Hopefully, the recently announced NCI guidelines will not

lead to the Swedes withdrawing this offer.’’ Could you explain what

that means?

Mr. BERRY. Apparently—and I am going from what John

Kuntzen said in the Chicago Tribune—the Swedes have agreed to

open up their studies to audit and analysis from other international people, including the NCI, and this was apparently due to

the controversy that has been going on in this country; they wanted to settle that controversy by doing what people have been asking them to do for many years. And I am concerned that they folVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00066 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
63

low through on that, and I hope that these proceedings and others

do not slow down that impetus.

Senator CLINTON. Well, what would it be about the NCI guidelines that would lead them to withdraw the offer?

Mr. BERRY. Well, there may be no more reason to open it up. If

there were——

Senator CLINTON. The fact that the NCI reiterated their guidelines.

Mr. BERRY. Yes.

Senator CLINTON. OK. It is not something in addition to that.

Mr. BERRY. No, no, no; just less uncertainty in this country.

Senator CLINTON. Well, I would hope that if there are any

Swedes out there, you do not withdraw the audit offer, because it

seems to me that we all have a common interest in trying to determine what the facts are insofar as that is possible.

Dr. Eyre, what are the international standards with respect to

mammography? Are you aware of what the recommended standards are in Europe or in Canada at this point?

Dr. EYRE. They vary depending on the health care system and

the recommendations that they make to the public. There are a

number of countries, including Sweden, who recommend mammography at age 40 or age 50, depending on the criteria that they use

and on an every-one-to-two-year basis. Great Britain recommends

mammography; a number of other countries do. Some in Europe do

not recommend mammography. The issue primarily before this last

discussion about the quality of the randomized trials has been on

a cost-benefit analysis basis rather than on an issue of reduction

in mortality.

There are some countries in the world where breast cancer is

much less common—in Asian countries—than it is in European or

North American countries, so for many of them, it would be less

important because of the decreased frequency, or the burden of the

disease is less.

In many European countries, the incidence and death rate of

breast cancer exceeds that in the United States and Canada, and

in those areas, some of them choose to do it, and some do not.

Senator CLINTON. Thank you very much.

I thank both of the panelists. I guess, having heard the testimony thus far and certainly having reviewed the written testimony, I think that although there may be questions and certainly

additional work that needs to be done, and this is obviously something to be weighed, I think I would weigh heavily the clinical experience and recommendations of Dr. Eyre as well as NCI, and I

think that until we learn otherwise, that seems to be the better

course of action. I appreciate the testimony.

Senator MIKULSKI. Thank you very much.

Mr. BERRY. Senator Mikulski, can I just make one comment

about something Dr. Eyre said, or is that out of order?

Senator MIKULSKI. No. As I said, it is a comment, but remember,

this is not a debate.

Mr. BERRY. OK. It is an occupational hazard that I have that I

complain about people who look at particular aspects of data that

make a point that they want to make and ignore other aspects.

64

Dr. Eyre pointed to the Cornell study that addressed the Malmo

trial and points out that if you look between years 8 and 11, you

get a benefit for screening. What they do not point out is that if

you look between years 3 and 6, you get a negative benefit for

screening. In fact, the increase in mortality between those years

was 58 percent—30 deaths versus 19 deaths. That study was really

very flawed, much more flawed than any of the trials that we are

talking about.

Senator CLINTON. Well, Dr. Berry, could I ask you—as far as I

am aware, there are only two widely utilized other forms of screening—either self-exam or clinical physician screening—is that right?

Mr. BERRY. That is as far as I know, yes.

Senator CLINTON. Right. So this is a crapshoot, right? I mean,

part of what we are trying to figure out here is that a lot of women

either cannot or will not do self-exams, do not know what they find

if they do them, and a lot of doctors may or may not have the same

clinical judgment that their neighbor down the hall might have.

So in each of these instances with respect to screening, we are

comparing, it seems to me, imperfect methods across the board. So

part of what we are attempting to do—and I think Senator Frist’s

questions certainly got to this point—it is of very little benefit for

most of us laypeople who are on the receiving end of conflicting advice to hear the difference between one and three and five and

eight and the rest of it, when we have to make a judgment. And

based on the best available information, and even based on many

of the most unequivocal statements in your own written testimony,

we put our odds with going ahead and having mammography,

knowing, as we know, that it is not the perfect answer. It is like

getting your teeth x-rayed; maybe the caries they find would never

turn into something that you would have to have filled or have a

tooth pulled, but you do the best you can with what information

you have.

Senator MIKULSKI. Thank you, Senator Clinton.

This concludes this panel. We want to thank you for your testimony and your contributions.

We now turn to a panel that includes the advocacy groups and

also testimony in behalf of the American College of Obstetricians

and Gynecologists.

We welcome Fran Visco from the National Breast Cancer Coalition; Dr. Carolyn Runowicz on behalf of the American College of

Obstetricians and Gynecologists, who is a constituent of Senator

Clinton, and she will introduce here; and Dr. Leffall, chairmanelect of the Susan G. Komen Breast Cancer Foundation.

Fran has been introduced by Arlen Specter, but for all those who

have been in the women’s health advocacy arena for some time, she

is a legend for her tireless and intrepid work to ensure that women

have access to the best health care and the best information. She

has received many awards and is herself a 14-year breast cancer

survivor. We look forward to her testimony.

Senator Clinton, do you want to introduce the good doctor?

Senator CLINTON. Thank you very much.

It is my pleasure to introduce Dr. Carolyn Runowicz, who is the

vice chairman of the Department of Obstetrics and Gynecology at

Saint Luke’s Roosevelt Hospital in New York. She faces the diVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00068 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
65

lemma of what to tell her patients about mammography every single day, in fact, many times a day. She is speaking on behalf of the

American College of Obstetricians and Gynecologists, and I am delighted that she could be with us on this panel.

Senator MIKULSKI. Thank you. We look forward to your testimony.

We turn also to Dr. LaSalle Leffall, who is chairman-elect of the

Susan G. Komen Breast Cancer Foundation. He comes to us as the

chairman of the Department of Surgery at Howard University, a

position he has held for more than 25 years, and he is going to

serve for 1 year as chairman of the Komen Foundation, which of

course has been one of the leading advocacy groups, well-known for

its Race for the Cure, and for not only raising money but also for

raising consciousness, as is Ms. Visco’s group, which represents

60,000 individual members and 500 groups in terms of grassroots

advocacy in terms of access, accuracy, and also challenging a lot of

the attitudes of the establishment.

Ms. Visco, we count you as a friend and an advisor, and we turn

first to you. We are glad to see all of you.

STATEMENTS OF FRAN VISCO, PRESIDENT, NATIONAL BREAST

CANCER COALITION, WASHINGTON, DC; DR.CAROLYN D.

RUNOWICZ, VICE CHAIRMAN, DEPARTMENT OF OBSTETRICS

AND GYNECOLOGY, SAINT LUKE’S ROOSEVELT HOSPITAL,

NEW YORK, NY, ON BEHALF OF THE AMERICAN COLLEGE OF

OBSTETRICIANS AND GYNECOLOGISTS; AND DR. LASALLE

LEFFALL, JR., CHAIRMAN-ELECT, SUSAN G. KOMEN BREAST

CANCER FOUNDATION, DALLAS, TX

Ms. VISCO. Thank you, Senator Mikulski and other members of

the committee, for inviting me to testify and for holding this hearing.

You have described the National Breast Cancer Coalition, so I do

not need to do that. But the question you have posed is ‘‘What do

women need to know?’’ Of course, the ultimate goal that we all

share is to save women’s lives.

Unfortunately, over the years, mammography has come to be

equated with breast cancer. Too many organizations, individuals,

and policymakers focus their breast cancer work on how to get

screening mammograms to healthy women. Yet you have heard

and read much about where we are in breast cancer and what the

future holds for this disease. We are learning more about the molecular basis of the disease. There is much more emphasis on how

to prevent this disease from occurring to begin with. We are talking more about the environmental links to breast cancer. We are

looking at targeted therapies. We are understanding that there are

many different types of breast cancer, and we are beginning to

learn how to treat them.

How do we detect breast cancer at its very early stages, and if

so, do we know what to do with it?

These are many of the questions that we are working on today.

It is an exciting time in breast cancer, and while we do not have

answers, there is much work to be done that will take billions of

dollars and much attention.

66

Yet we continue to spend billions of dollars on mammography.

Where is this other money going to come from? These are priorities

that must be set based on solid scientific evidence.

I want to make a couple of comments in response to statements

that were made earlier. First of all, we must be clear that mammograms do not prevent breast cancer. We really do not know how to

prevent breast cancer for any individual woman.

No. 2, the data show that there are more mastectomies in the

groups in the trials that are screened by mammography than in

the control groups. That is an important point when we begin to

talk about quality of life in this issue.

Also, it is important to know that biostatisticians are experts in

this debate; they are experts in looking at clinical trials, designing

them, and interpreting data on which clinical decisions must be

made.

But again, your question is ‘‘What do women need to know?’’ Well, they need to know the truth. Our goal should not be to provide a clear, simple message. Our goal here should be let us find

the truth about what will save women’s lives, and let us get that

information and those interventions to women.

A clear, simple message, while comforting, is not necessarily correct. This is an incredibly complex issue, as you can tell—lead time

bias, length bias. There are renowned scientists on every side of

this issue, questions about the trials, many of which are important

substantive questions; questions about how to interpret results,

what are the risks—and a false positive is not the only risk of a

mammogram—what are the benefits, how do we quantify them.

We cannot pretend that this complexity and these controversies

do not exist, and it cannot be resolved simply by issuing a clear,

simple guideline.

I am not going to address the complexities of the trials. I was a

reviewer for the U.S. Preventive Task Force. I disagreed with their

recommendations. I have spent a great deal of time analyzing the

information, analyzing the data, and my written testimony addresses those issues—my written testimony which I submit for the

record together with the Question and Answer that the National

Breast Cancer Coalition has put together for the public on these

issues.

I trust women. I think women are quite capable of understanding

complexity and dealing with medical uncertainty. At the National

Breast Cancer Coalition, we have developed a number of programs

to educate the public about these issues, to give them the tools to

enable them to deal with the uncertainty and to seize the power

to make informed decisions. This includes the Q and A I referenced, a number of science and advocacy training programs.

So the goal is truth, not just clarity and a simple message; and

the truth seems to be that there is uncertainty about the evidence

or about the existence, or if it exists, the extent of the benefits of

screening mammography. Some will say 30 percent reduction in

mortality, others will say 20, some will say none. We have heard

about lead time and length bias; do we save lives or simply add

days to lives.

These are all legitimate issues that women are capable of understanding and making their own choices on.

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I have just two more quick points. If the goal is to save women’s

lives, if we had taken the billions of dollars put into building an

infrastructure for screening mammography and breast self-exam

videos and shower cards, and provided health insurance for the

women of this country, I think we would have saved many more

lives.

A woman testified on behalf of the Coalition last year for the

CDC treatment legislation about her support group sharing one

prescription for tamoxifen because the other women did not have

health coverage. That is the reality of what women with breast

cancer are facing. And again, that would save more lives—I believe

even the most ardent supporter of mammography screening would

admit that.

So let us focus our efforts now on getting an independent review

of the Swedish data on the screening trials by an organization such

as MedicoLegal Investigations in the UK; let us get the best possible answer we can for women under the circumstances, and let

us move on. Let us find out how to prevent this disease, how to

detect it truly early, how to get nontoxic therapies, and how to get

quality care to all women. And finally, let us reauthorize the Mammography Quality Standards Act, because diagnostic mammography will continue, as will screening mammography, and we need

to make certain that it is done well.

Thank you very much.

Senator MIKULSKI. Thank you, Ms. Visco. As always, you raise

eyebrows.

[The prepared statement of Ms. Visco follows:]

PREPARED STATEMENT OF FRAN VISCO

Thank you, Chairmen, members of the Senate Health, Education, Labor and Pensions Aging Subcommittee, and members of the Senate Appropriations Labor,

Health and Human Services and Education Subcommittee, for your dedication and

leadership in working with the National Breast Cancer Coalition (NBCC) in our

fight to eradicate breast cancer.

I am Fran Visco, a breast cancer survivor, a wife and mother, a lawyer, and President of the National Breast Cancer Coalition.

The National Breast Cancer Coalition is a grassroots organization dedicated to

ending breast cancer through the power of action and advocacy. The Coalition’s

main goals are to increase Federal funding for breast cancer research and collaborate with the scientific community to design and implement new models of research;

improve access to high quality health care and breast cancer clinical trials for all

women; and, expand the influence of breast cancer advocates in all aspects of the

breast cancer decision making process.

On behalf of NBCC, which is made up of more than 600 member organizations

and 70,000 individual members, I would like to thank you for the opportunity to

testify today on this critically important issue.

I believe it’s very important to put the current debate about the effectiveness of

screening mammography in the right context. What this debate is really about is

saving women’s lives, and improving the quality of their lives—not about attacking

or defending mammography. For decades, mammography has been linked to preventing breast cancer deaths. We used to think that the earlier we catch breast cancer, the easier it will be to treat. Yet, we are beginning to better understand the

complexities of this disease. And we are realizing that the concept of early detection

being the key to reducing mortality may not be the whole story. Some very small

cancers can be very aggressive, regardless of when they are detected, and other big

tumors caught later may never cause a death. We must consider screening mammography, not only in terms of how early and effectively it detects tumors, but also

in terms of the impact early detection will have on a woman’s treatment options in

light of what we now know about this disease.

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We also must be clear about the realities and limitations of the early detection

tools that exist today. Currently, there is no truly early detection. Often, by the time

a tumor is found, it has been in the breast for 6 to 10 years. The goal must be to

detect the tumors at their earliest stage, or prevent them in the first place.

Mammography should be accepted for what it is: followed by treatment, it may

extend the lives of some women who have breast cancer, but it does not prevent

or cure breast cancer, and it has many limitations.

At best, this is simply not good enough. We need more reliable and less invasive

tools developed to detect breast cancer. We need more targeted and more effective

treatments for this disease and a better understanding of how one tumor differs

from another. And, we need a clearer understanding of what causes this disease,

and how to prevent it.

It is also important to keep in mind that this debate is not about diagnostic mammography (for women with symptoms of breast cancer), but about screening mammography (the healthy population of women). This issue must be considered in the

context of the limited health care dollars available for breast cancer. What are the

best use of resources to reduce mortality and improve quality of life for women?

The National Breast Cancer Coalition respects the difficult challenge in developing a public health message, which may differ from the personal decisions that individual women and their doctors will make. But, our goal today is to explain what

we do and do not know about how to reduce breast cancer mortality. The truth is

not always clear, but we believe that women deserve to be fully informed, and that

they are capable of understanding the complexities around this disease.

BACKGROUND

The National Breast Cancer Coalition believes that the debate over the effectiveness of mammography in reducing breast cancer mortality is vitally important. For

too long, mammography has been inextricably and erroneously linked with ‘‘prevention’’ of breast cancer. Mammography screening of women age 40 and above has become the standard of care for women in the United States. It has become a multibillion dollar business. Organizations exist solely to raise awareness about mammograms and breast self-examination. Legislation has proposed to teach high school

students about breast self-examination. Campaigns directed to the public about the

importance of screening are increasing in number. For much of the public, mammography is the most important, if not the only, issue in breast cancer.

Women are told that early detection saves lives. Yet, the evidence of mortality reduction from screening is conflicting and continues to be questioned by scientists,

policy makers and some members of the public. Breast self examination has become

part of the culture of breast cancer, even though there is no evidence whatsoever

to support its efficacy.

The fact that breast cancer screening is now high on this nation’s agenda must

not color the analysis of the evidence. Recommendations on breast cancer screening

must have as their goal saving women’s lives, not preserving an infrastructure.

In my testimony today, I will make four major points.

First, I will explain NBCC’s position on mammography screening.

Second, I will respond to the recent studies about what more we now know regarding the effectiveness of mammography reducing mortality.

Third, I will discuss what these new data mean for women, and for the decisions

they must make.

Finally, I will give NBCC’s recommendations for where we need to go from here.

THE NATIONAL BREAST CANCER COALITION’S POSITION ON SCREENING MAMMOGRAPHY

The National Breast Cancer Coalition has long acknowledged the limitations of

mammography screening. For years, NBCC has said that mammography is not the

answer to the breast cancer epidemic. Although it may be difficult to accept, it is

vital that women know the truth about breast cancer screening and the false sense

of security it provides. As breast cancer activists, NBCC welcomes the long overdue

criticism and discussion of the effectiveness of existing breast cancer screening

methods.

We must accept that we do not know how to detect breast cancer truly early or

how to prevent or cure this disease. Instead, we should focus our attention on getting those answers. NBCC believes the goal must be to focus research efforts on true

prevention and on stopping breast cancer from occurring altogether. We must work

together to find new, more accurate ways to detect and treat this disease.

The Coalition also believes that women who have access to mammography must

have access to treatment. Screening alone does not reduce mortality. It is for that

reason that NBCC was proud to be the originators, and lead advocates on working

69

with Members of Congress, many who sit on your Committees, to enact the Breast

and Cervical Cancer Treatment Act in the 106th Congress. As you know, this law

ensures that low-income women screened and diagnosed with breast cancer through

Federal programs can now have access to the treatment they need. NBCC had to

fight four, very long, hard years to get women in this program treated as well as

screened. There was a lot of opposition along the way, mainly because people were

afraid that we were criticizing screening. This debate must not be about saving

screening, but rather, about reducing breast cancer mortality. It is about women’s

lives.

NBCC also believes that mammography should be of the highest quality possible.

The Coalition commends your Committees’ leadership in enacting the Mammography Quality Standards Act (MQSA), which established minimum national quality

standards for mammography facilities and personnel as well as a rigorous annual

inspection program to ensure those standards are being met. We appreciated the opportunity to testify before Congress during reauthorization of this program in 1998,

at which time we urged that the women be notified directly of the results of their

mammogram, and that Congress continue to ensure the highest quality mammography by maintaining the rigorous inspection process initially contemplated.

NBCC supports reauthorization of this important program this year, and would

be happy to provide the Committee with additional information or recommendations.

NBCC’S RESPONSE TO THE EVIDENCE

The National Breast Cancer Coalition’s general position on mammography is that

guidelines on mammography screening should only be issued if scientific studies

prove that such programs save lives, and if the benefits outweigh the risks.

As your Committees know, there are seven published randomized trials of mammography screening. The oldest of these trials, the New York Trial, was conducted

in the 1960’s. Four of the trials were conducted in Sweden, one was conducted in

Canada, one was conducted in the United Kingdom, and one was conducted in the

United States. The seven trials are known as:

The New York trial or HIP trial—enrolled women 40–64

The Malmo trial—enrolled women 45–69

The Two-County trial—enrolled women over age 40

The Edinburgh trial—enrolled women ages 45–64

The Canadian trial (parts 1 and 2)—enrolled women ages 40–59

The Stockholm trial—enrolled women ages 40–64

The Goteborg trial—enrolled women ages 39–5

Two of these trials—the Malmo and Canadian trials—found that mammography

did not benefit women. In these trials, the women who got mammography screening

had the same breast cancer mortality as the women who did not. The other five

trials found that mammography did benefit women and reduce breast cancer mortality by about 30% on average. Although a majority (five of seven) of the trials found

that mammography is beneficial, we cannot simply conclude that mammography

saves lives.

First, the reliability and quality of each trial must be evaluated. Some trials may

have been poorly carried out, and some trials may not be applicable to the general

population of women. Also, it is important to note that a majority of trials does not

necessarily represent a majority in the number of individuals who participated in

the trials.

Many scientists have critiqued these trials, however, the most thorough peer reviewed evaluation to date was recently conducted by Drs. Gotzsche and Olsen, Danish scientists affiliated with the well-respected Cochrane Collaboration. These scientists set out to review and evaluate all seven of the mammography trials to determine the quality of each. The authors had no conflicts of interest and were unbiased

at the start of the review. Their findings were published in a recent issue of The

Lancet medical journal as a systematic review.

The findings of the systematic review prompted an independent panel of experts

(the PDQ screening and prevention editorial board) at the National Cancer Institute

to conduct its own evaluation of the seven mammography trials. After its review,

the panel concluded that there is insufficient evidence to show that mammography

screening prevents breast cancer deaths in any age group of women. Moreover, it

concurred with Drs. Goetze and Olsen that the Malmo and Canadian trials were the

highest quality trials, and that they did not show that mammography reduces

breast cancer mortality. Finally, the review found that mammography could also

have negative effects—including more aggressive treatment and more unnecessary

surgeries.

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The authors of the systematic review do not state that there is proof that mammography is ineffective. Rather, the evidence is unclear.

Most recently, the U.S. Preventive Services Task Force (USPSTF) recommended

screening mammography, with or without clinical breast examination, every one to

two years for women ages 40 and over. The Department of Health and Human Services (HHS), and the National Cancer Institute (NCI), have endorsed these recommendations.

NBCC believes that these recommendations were premature and that the Task

Force should not have made recommendations until the individual data is released

by the Swedish investigators and analyzed by an independent review.

It seems clear that in a situation like the present, where data exist that could

answer the questions posed, those data should be released and analyzed before recommendations are made. In addition, the fact that data exist that could help answer

the question of whether screening results in fewer breast cancer deaths, but more

deaths from other types cancer or other causes, should have compelled the Task

Force to demand the data before it made recommendations.

Moreover, the Task Force relied on evidence to recommend screening mammography for women age 40–49 that clearly does not rise to a level sufficient to support

screening. In fact, only one trial was designed to answer the question of screening

in women aged 40–49, and it found no benefit. In the remaining trials, women in

that age group were a cohort of the larger population. In previous recommendations,

the Task Force did not recommend screening women in this age group; since there

is no new data to show a benefit for these women, it is unclear why the Task Force

changed its recommendation.

WHAT DOES THIS MEAN FOR WOMEN TRYING TO MAKE INFORMED HEALTHCARE

DECISIONS?

The National Breast Cancer Coalition believes strongly that women deserve to

know the truth. If the truth is that evidence is unclear, then they should know that.

Progress in eradicating breast cancer means accepting uncertainty regarding best

treatment and detection methods. Women and doctors have to understand, and live

with this uncertainty, understand the risks, and make individual decisions.

This issue is not black and white. The public needs to accept uncertainty, and

move toward educating themselves so they can make their own decisions on an individual basis. Women are capable of understanding that to date, no screening tool

allows for truly early detection of breast cancer. Meaning, by the time a tumor is

detected, it has been in the breast for 6–10 years. Women also need to understand

that some cancers will never spread to other parts of the body, so detecting these

cancers won’t save lives—rather, treatment would be unnecessary, and possibly

harmful. We just don’t know.

WHERE DO WE GO FROM HERE?

First, the National Breast Cancer Coalition believes that the most useful thing

we can do now is make certain that there is an independent review of the data.

NBCC would like to first better understand what the results of these trials mean.

The Swedish researchers must allow all of the individual data to be released to an

independent reviewer like Medico Legal Investigations, Ltd. in Knebworth, England.

This may resolve many of the concerns and questions raised by Drs. Gotzsche and

Olsen, and may provide better answers about the effectiveness of mammography.

Second, the cost of mammograms cannot be ignored. Remember, we are not talking here about women who have been diagnosed with a disease. We are talking

about the screening of a healthy population of women. Mammography screening is

a multi-billion dollar expenditure. We must ask ourselves whether this is the best

expenditure of finite dollars? Especially in light of the fact that we know using these

resources to buy healthcare for underserved and uninsured women would unquestionably reduce mortality.

We must ask the critical questions: What is the best use of resources? What are

the pros and cons? This is a debate that must happen. These are the issues that

we must grapple with before we decide to just accept the status quo.

Finally, NBCC urges the public not to just sit and fret over the lack of clear consensus on mammography. Instead, we need to be advocating for more research and

resources going towards true prevention and better methods of treatment and detection.

Precious time, resources and attention continue to be diverted away from promising research and funneled into an oversold panacea for breast cancer detection. The

issue is about saving women’s lives, not saving the institution of mammography. We

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must continue to look ahead of the curve to see what more can be done regarding

prevention and detection. Only then will we be able to eradicate this disease.

I want to thank these Committees for the opportunity to testify today. I have enclosed NBCC’s Question and Answer document on mammography, and ask that it

be included in the record. I would be happy to answer any questions.

Senator MIKULSKI. Dr. Runowicz, please.

Dr. RUNOWICZ. Good afternoon, Madam Chair and distinguished

members of the subcommittee. I appreciate your invitation to testify today on behalf of the American College of Obstetricians and

Gynecologists, or as it is better known, ACOG.

I am a practicing physician who is no stranger to dealing with

concerned patients when scientific controversies raise questions

about their health and safety. In this particular debate, I also wear

a third hat—I am a 10-year breast cancer survivor.

The American College of Obstetricians and Gynecologists represents nearly 40,000 physicians dedicated to improving women’s

health care. Our members are seeing women on the front lines of

the breast cancer struggle. We provide women with clinical breast

exams, refer them most often for mammography, and often make

the diagnosis of breast cancer. Some of us, like myself, are also

gynecologic oncologists and assist in the treatment plan.

ACOG agrees that an extensive and objective reassessment of all

mammography data may be justified. Until further reanalysis of

the data is conducted, ACOG continues to recommend mammography screening every one to 2 years for women in their 40’s and

annual mammograms beginning at age 50.

We are here today because of publicity surrounding a study done

by Danish researchers recently published in Lancet. The Lancet

study questions one of the most widely held beliefs in preventive

medicine—that screening healthy people for cancer and detecting it

early saves lives. It is important to note that this is not a new

study but a reanalysis of already existing published data.

Scientific debate on critical issues like this one is common.

ACOG supports periodic, evidence-based, peer-reviewed analysis of

all available data on mammography, including a review of studies

like the one in Lancet. We take its criticism of prior mammography

research very seriously, and we want to make sure that the Lancet

study itself stands up to rigorous review.

In fact, the U.S. Preventive Services Task Force announced last

week a different conclusion than that of the Lancet study. Their review of the data found that breast cancer deaths among women

randomized to screening in seven trials that included women older

than 50 showed a 23 percent reduction in mortality. And contrary

to prior testimony that you have heard today, in 1993, an independent analysis of the actual data from the five Swedish trials

cited in the Lancet study showed a statistically significant 24 percent reduction in breast cancer mortality in the screened group.

With such conflicting data, where do we go from here?

Initially, I think that all of us—Members of Congress, doctors,

patients, journalists, researchers—need to understand the difference between the very rigorous standards that scientific evidence must meet to clearly prove the worth of a test and the

proctocolitis of what must be done in physicians’ offices when conclusive scientific evidence (1) is not yet available or (2) may never

be available.

72

I make this second point because at this time and in the future,

there would be clear ethical and moral problems in performing a

randomized prospective clinical trial in breast cancer screening

that medical scientists say are the highest qualify of scientific

proof. How many women today would be willing to go without

breast cancer screening in a clinical trial to prove or disprove a statistical point? We may have to live with a certain amount of uncertainty when it comes to the results of mammographic screening

trials.

I also think we need to educate our patients about the facts behind the recent media hype—and that is what this is all about—

media hype. While the Lancet study has raised several important

issues, as a practicing physician, I have to look at this through the

eyes of individual patients. I explain to patients that this debate

has nothing to do with the effectiveness of breast cancer treatment.

There is agreement that treatment saves lives. Instead, the debate

is whether earlier treatment made possible by the early detection

of tumors is better than later treatment.

I tell them that early treatment made possible by early detection

does make a difference. I explain why I think the accumulation of

research trial evidence over the years has strengthened the science

behind breast cancer screening and that the data in aggregate

demonstrate improved health outcomes, with benefits outweighing

the harmful effects.

I discuss the recent controversy and my own recommendations.

I explain that scientific debate on critical issues is common, but

well-established guidelines should be followed unless there is compelling evidence to alter or abandon them.

The news stories have already had a large impact on patients.

They are confused, and they express a loss of faith and confidence

in mammography. Some even misinterpret the media coverage and

take away the message that mammography is bad and even causes

cancer.

Over the years, we have made significant strides in educating

women about mammography by breaking down financial, physical,

and psychological barriers to women seeking mammographic

screening. I fear, as does ACOG, that these barriers might be reinforced by this negative attention and uncertainty generated by the

media hype.

As already mentioned by Senator Mikulski, I and ACOG are also

deeply concerned that the ongoing controversy might discourage

health insurance plans from covering this important screening tool.

As frustrating as this controversy may be to women suffering

from breast cancer, the silver lining is that it brings to light a goal

that we all share—the need to be even more vigilant in supporting

research efforts to enhance not just early detection, but treatment

as well as prevention and finding a cure for breast cancer. Until

then, mammography remains as one of a number of strategies that

can help save or improve women’s lives.

Even if the screening tests that we have now are not as good or

as conclusive as we would like, they are the best we have at the

moment. As a practicing physician, I would be derelict in my duties

if I advised women to stop having mammograms.

73

On behalf of ACOG and my patients, I thank you for holding this

hearing and for the opportunity to testify today. I would be happy

to answer questions.

Senator MIKULSKI. Thank you very much, Doctor.

[The prepared statement of Dr. Runowicz follows:]

PREPARED STATEMENT OF CAROLYN D. RUNOWICZ, M.D.

My name is Carolyn D. Runowicz, and I appreciate your invitation to testify

today. I appear before you on behalf of the American College of Obstetricians and

Gynecologists (ACOG), and as a practicing physician who is no stranger to dealing

with concerned patients when scientific controversies raise questions about their

health and safety. In this particular debate, I also wear a third hat: I am a 10-year

breast cancer survivor.

The American College of Obstetricians and Gynecologists (ACOG) represents

nearly 40,000 physicians dedicated to improving women’s health care. Ninety-five

percent of board-certified obstetricians and gynecologists in the United States are

members of ACOG. Our members are seeing women on the front lines of the breast

cancer struggle: we provide women with clinical breast exams, refer them most often

for mammography, and often make the diagnosis. Some of us, like myself, are

gynecologic oncologists and assist in treatment plans.

I am currently Vice Chair of the Department of Obstetrics and Gynecology at St.

Luke’s-Roosevelt Hospital in New York City. I also serve as Director of Gynecologic

Oncology Research for the Women’s Health Service Line of Continuum Health Partners, Inc. and I am Professor of Obstetrics, Gynecology and Women’s Health at Albert Einstein College of Medicine (AECOM). Since 1994, I have chaired the

gynecologic subcommittee of the Breast Cancer Prevention Trials that are part of

the National Surgical Adjuvant Breast and Bowel Project.

ACOG agrees that an extensive and objective reassessment of all mammography

data may be justified. In fact, ACOG continually updates its own clinical recommendations by periodically reviewing all data. Until further reanalysis of the

data is conducted, ACOG continues to recommend mammography screening every

one to two years for women in their forties and annual mammograms beginning at

age 50.

We are here today because of publicity surrounding a study done by Danish researchers, members of the Cochrane Collaboration, recently published in Lancet (referred to here as the Lancet study). The Lancet study questions one of the most

widely held beliefs in preventive medicine: that screening healthy people for cancer

and detecting it early saves lives. It is important to note that this is not a new

study, but a re-analysis of published data.

Scientific debate on critical issues like this one is common. ACOG supports periodic, evidence-based, peer-reviewed analysis of all available data on mammography—including a review of studies like the one in Lancet. We take its criticism

of prior mammography research very seriously, and we want to make sure the Lancet study itself stands up to rigorous review.

In fact, the U.S. Preventive Services Task Force (USPSTF) announced last week

a different conclusion than that of the Lancet study. The USPSTF review of the data

found that the pooled effect size of the combined trials was sizable and statistically

significant. Breast cancer death among women randomized to screening in seven

trials that included women older than 50 showed a 23 percent reduction in mortality.

In addition, an earlier independent analysis of individual-level data from the five

Swedish trials cited in the Lancet study, conducted under the auspices of the Swedish board of health and published in 1993, showed a statistically significant 24 percent reduction in breast cancer mortality in the screened group.

With such conflicting data, where do we go from here?

Initially, I think all of us—members of Congress, doctors, patients, journalists, or

researchers—need to understand the difference between the very rigorous standards

that scientific evidence must meet to clearly prove the worth of a test, and the

practicalities of what must be done in physicians’ offices when conclusive scientific

evidence (1) is not yet available, or (2) may never be available.

I make this second point because at this time and in the future there would be

clear ethical and moral problems in performing the randomized, prospective clinical

trials in breast cancer screening that medical scientists say are the highest quality

of scientific proof. I ask you: how many women today would be willing to go without

breast cancer screening in a clinical trial to prove or disprove a medical researcher’s

74

point? We may have to live with a certain amount of uncertainty, when it comes

to the results of mammographic screening trials.

I also think we need to educate our patients about the facts behind the recent

media hype on the usefulness of mammography. While the Lancet study has raised

several important issues and I am very interested in the scientific debate, as a practicing physician I have to look at this through the eyes of individual patients.

It is important to explain to our patients that this debate has nothing to do with

the effectiveness of breast cancer treatment. There is agreement that treatment

saves lives. Instead, the debate is whether earlier treatment made possible by early

detection of tumors is better than later treatment.

Then I explain why I believe that early treatment does make a difference. I am

very careful to explain to women that early diagnosis combined with early treatment translates for many women into a better future. I believe that early detection

in most cases helps us to prolong women’s lives, even those destined to die from

breast cancer. Early diagnosis can affect the quality of women’s lives in positive

ways.

I explain why I think the accumulation of research trial evidence over the years

has strengthened the science behind breast cancer screening. There has been an important decline in death rates from breast cancer, nearly 2 percent every year during the 1990s and nearly 4 percent since the mid-90s, which has been attributed

to improvements in treatment and a trend towards earlier detection. In the 1980s,

only 13 percent of U.S. women were getting mammograms and the average size of

tumors was 3cm. By the late 1990s, 60 percent of women were having regular mammograms and the average size of tumors decreased to 2cm.

So, I note that although mammography is not a perfect screening tool, it is very

effective. Mammography can have false-positive results, which may cause anxiety,

biopsies, and cost—although these diminish from ages 40–70. However, the data in

aggregate demonstrate improved health outcomes, with benefits outweighing the

harmful effects.

I discuss the controversy and my own recommendations noting of course that the

decision on whether to be screened is theirs. I explain that scientific debate on critical issues is common, but well-established guidelines should be followed unless

there is compelling evidence to alter or abandon them.

The news stories have already had a large impact on patients. They are confused

and express a loss of faith and confidence in mammography. Some misinterpret the

media coverage and take away the message that mammography is ‘‘bad’’ and can

even cause cancer!

Over the years, we have made significant strides in educating women about mammography by breaking down financial, physical, and psychological barriers to

women seeking mammography screening. I fear that existing barriers and negative

attitudes towards mammography might be reinforced by the negative attention and

uncertainty generated by the media hype. It is too soon to know if women will turn

away en masse from mammography and we will turn the clock back in the fight

to treat breast cancer. I am also deeply concerned that the ongoing controversy

about the value of screening mammography might discourage health insurance

plans from covering this important screening tool.

As frustrating as this controversy may be to the women suffering from breast cancer, the silver lining is that it brings to light a goal I think we all share: the need

to be even more vigilant in supporting research efforts to enhance not just early detection but also treatment, as well as prevention and finding a cure for breast cancer. Until then, mammography remains as one of a number of strategies that can

help save or improve women’s lives.

Even if the screening tests we have now are not as good or as conclusive as we

would like, they are the best we have at the moment. As a practicing physician, I

would be derelict in my duties if I advised women to stop having mammograms.

On behalf of ACOG and my patients, I thank you for holding this hearing and

for the opportunity to testify today. I am happy to answer any questions.

Senator MIKULSKI. Dr. Leffall, we would be happy to hear your

testimony in behalf of the Komen Foundation.

Dr. LEFFALL. Thank you very much, Senator Mikulski and other

distinguished members of the committee.

As a surgeon oncologist and medical educator, I have devoted

most of my professional life to the study of cancer. After I completed my surgical oncology training and Memorial Sloan Kettering

Cancer Center and 2 years in the Army, I returned to Howard UniVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00078 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
75

versity in 1962 and have been there since then, so this is now my

41st year on the surgical faculty at Howard and my 41st year in

the active practice of surgical oncology, and the major part of my

practice consists of patients who have breast problems; thus my

major interest in this.

The Komen Foundation was established some 20 years ago by

Nancy Brinker to honor the memory of her sister, Susan Goodman

Komen, who died of breast cancer at the age of 36. Today the

Komen Foundation is the Nation’s largest private funding sources

of breast cancer research and community-based outreach programs.

Modern medicine is fully of uncertainty, but today the assault on

mammography has created a cloud of confusion and an atmosphere

of suspicion. It has also done a true injustice to American women

who understand that screening is not prevention. We are not surprised, but certainly we are disappointed.

That said, we concur with the expert opinion of our times—mammography is an imperfect screening tool and one that should be

made better. But we want to emphasize that we think it is the

most appropriate thing now for women, screening mammography.

While we are working to unlock the secrets of what causes breast

cancer and eventually prevent the disease for future generations of

women, the Komen Foundation understands the realities facing

women and their families today. Therefore, the Foundation applauds the mammography screening recommendations reported

last week by the U.S. Preventive Services Task Force and the National Cancer Institute.

Affiliates of the Komen Foundation currently provide grants for

more than 1,600 breast health education and breast cancer screening and treatment projects in their communities. In addition, the

Komen Foundation Research Program awarded more than $20 million in grants during the last year alone to support cutting-edge research in institutions around the globe.

As someone who is on the front lines and seeing patients every

day with breast problems, many of whom have breast cancer, I

know firsthand how both mammography and breast cancer treatment have changed during the last 20 years. Mammography is better. The radiologists are better. The technicians are better.

Two of the crown jewels of health care policy in the United

States, both of which came about in the last decade, are the Mammography Quality Standards Act and the CDC’s Breast and Cervical Cancer Early Detection Program. Senator Mikulski, the

Komen Foundation applauds your efforts and being a leader in the

MQSA. It is so important to ensure the high quality of mammography for women. We know that quality mammography certainly

saves lives.

Mammography screening to reduce breast cancer mortality must

be sensitive enough to detect the disease. Poor-quality mammography reduces the sensitivity and specificity of the screening test.

The use of dedicated, up-to-date equipment is key to the performance of high-quality screening tests. Since the MQSA enactment,

women throughout this country have gained further confidence in

their mammogram.

My next statement was alluded to by Senator Murray earlier

today. In the early 1980’s, when only 13 percent of women in the

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United States were getting mammograms, the average tumor size

at detection was about 3 centimeters. By the late 1990’s, when 60

percent were getting mammograms, the average detected tumor

size was 2 centimeters. For many women, early detection means

the possibility of less invasive treatments in some cases as well as

the option of breast conservation surgery instead of mastectomy.

In the past decade, breast cancer mortality rates have declined

in the United States, and Dr. von Eschenbach showed that on his

charts. This is due in large measure to early detection and timely

treatment. That is important—early detection and timely treatment.

Regular mammography as part of a three-step breast health regimen that includes monthly breast self-exams and annual clinical

exams saves lives. It enables women, as true partners in their

health care, to become familiar with the normal look and feel of

their breasts.

While mammography can sometimes lead to false negative results when a woman and her caregiver discover a suspicious lump

that did not show up on a mammogram, further examination does

not always entail surgery. We have means now of making a diagnosis with image-guided biopsies and tests like that.

There is also the risk of false positive results, and an abnormal

mammogram is in fact not breast cancer, which may also result in

further tests.

But while these risks may result in unnecessary procedures for

some women, our constituents in America’s communities tell us

that even these serious consequences seem acceptable if they are

faced with the possibility of a life-threatening disease.

We encourage the Senate to allow steadfast hearts and large

minds to rule the day and advocate instead for the recommendation

of the U.S. Preventive Services Task Force to take advantage of the

only widely available screening tool currently proven to find breast

cancers before they grow to the size that can be felt by hand.

The National Cancer Institute declares that the evidence will not

support a change in their recommendations. We at the Komen

Foundation will remain true to our recommendations as well.

Thank you for this opportunity to appear before you today, Senator Clinton and Senator Mikulski.

[The prepared statement of Dr. Leffall follows:]

PREPARED STATEMENT OF LASALLE D. LEFFALL, JR., M.D.

On behalf of the Susan G. Komen Breast Cancer Foundation, thank you Senator

Mikulski, Senator Harkin, Senator Frist, and Senator Specter and other committee

members here today, thank you for creating a forum for public discussion on the

most recent debate on breast health.

The Komen Foundation is one of the largest private funding sources for breast

cancer research today, and was begun by Nancy Brinker 20 years ago in honor of

her sister, Susan Goodman Komen, who died of breast cancer at the age of 36.

Helen Keller has long been a hero of Nancy’s, and she once said, ‘‘Doubt and mistrust are the mere panic of timid imagination, which the steadfast heart will conquer, and the large mind transcend.’’

Modern medicine is full of uncertainty... This can be purposeful, however, for

it is uncertainty which lends life its fascination when partnered with the desire to

comprehend. But today, the assault on mammography has created a cloud of confusion, an atmosphere of suspicion, and an injured party of women. Discounting the

power of uncertainty, the recent debate has thrust ambiguity upon this significant

subject of public health. Unproductive reiteration of the relative merits of various

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scientific inquiries has created confusion. We’re not surprised, but we are disappointed.

Imagine two computers on one hand, and a couple of mastermind logicians on the

other, testing which group analyzes chess moves more advantageously. Would you

be surprised if your results were conflicting if one computer had a Pentium Chip,

and the other did not?

The ‘‘Pentium Chips’’ of Mammography in the United States are the Mammography Quality Standards Act, the BCCEDP, and other new initiatives of the last

decade. The vast improvements in film, machinery, training, and access are part

and parcel to mammography’s ‘‘Pentium Chip’’. That said, we concur with the expert opinion of our times. Mammography is an

imperfect screening tool. We are investing heavily in better technologies. Yet, we

know improvements take time. So while we are working to improve early detection

and eventually uncover true forms of prevention, the Susan G. Komen Breast Cancer Foundation applauds the mammography screening recommendations reported

last week by the U.S. Preventative Services Task Force and the National Cancer

Institute.

The Komen Foundation will continue to recommend the three-step approach to

positive breast health including monthly self breast examinations beginning at age

20; clinical breast examinations at least once every three years beginning at age 20

and annually after age 40; and annual screening mammography beginning at age

40.

The Task Force’s recommendations, underscored by Secretary Thompson’s re- marks, take us one step closer to clearing the confusion. Because, before women

start canceling screening mammography appointments, we need clear guidelines for

those making the decision today about their health care based on the best currently

available information and technology. Until a foolproof mechanism of detection is

widely available, the Komen Foundation strongly encourages women to continue

having mammograms.

At the same time, the Komen Foundation will continue to focus research dollars

on improving the quality of screening technology as well as research that will one

day lead to a cure for breast cancer. The Komen Foundation Research Program

awarded more than $2.4 million in grants last year to support institutions conducting cutting-edge imaging technology research. In total, the Komen Foundation awarded $20 million in research grants last year

in support of the fight against breast cancer, it’s eventual cure, prevention and

eradication. In addition, Komen Affiliates provided grants for more than 1,600

breast health education, screening and treatment projects in 116 communities

across the country.

Since 1998, the Komen Foundation Research Program has funded grants to im- prove breast imaging technology totaling $3,320,927. We have also funded considerable research aimed at finding a way to cure or prevent breast cancer, to wit: proteins associated with breast cancer totaling $4,786,144; Angiogenesis totaling

$754,148; Oncogenes totaling $1,845,348; Growth Factors totaling $4,051,553; Antibodies totaling $2,998,787; and BRCA genetic abnormalities totaling $2,082,024.

Please find detailed information about grants in each category as an addendum to

my testimony.

The benefit of early detection is undisputed, but with it comes the potential risks

for additional procedures and/or over-treatment. ‘‘False-positive’’ results may lead to

further imaging or biopsy that end up with a benign finding. When there are historic data (i.e., previous mammograms) for comparison, however, the rate of false

positives can be decreased, thus the need for regular screening rather than a onetime view only.

The detection of breast cancers that may never have progressed to a dangerous

stage during a patient’s lifetime also counts toward the ‘‘risk’’ side of the equation.

But since we don’t know which breast cancers will progress, virtually all these

women are treated surgically, with or without radiation and chemotherapy. And

while these risks may result in unnecessary procedures or treatment for some

women, our constituents in America’s communities tell us that even these serious

consequences seem acceptable if they are faced with the possibility of a life-threatening disease.

Mammography can also sometimes lead to false-negative results. For this reason,

when a woman and her caregiver discover a suspicious lump that did not show up

on a mammogram, it should be examined by other means—but that doesn’t always

entail surgery. There are well-accepted alternative ways of assessing whether a

lump detected through clinical exam, or even an abnormal mammogram, is breast

cancer other than through surgical biopsies. These methods include MRI,

ultrasound, and ultrasound-guided or stereotactic (x-ray guided) biopsy. The cost of

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making a breast cancer diagnosis is lowered dramatically by appropriate use of

ultrasound and image-guided biopsies.

So, while we have the potential for false-negative and false-positive findings on

the one hand, we have the case for early detection on the other. The larger the

tumor, the longer or faster it has been growing. This often translates into more aggressive treatment, as larger tumors are more likely to have spread beyond the initial site. And even with more treatment, the survival chances of women with larger

tumors is not as good as those with tumors smaller in size.

As previously stated, the Komen Foundation is funding research into new imaging

technology with a goal of diminishing false-positive and false-negative outcomes.

Further, and more critically, we are funding research to identify which tumors in

which women are likely to spread aggressively and become life-threatening. Our

funding of studies of molecular markers associated with breast cancer or other abnormalities, including inherited genetic changes, tumor growth factors and gene proteins, totaled nearly $3 million in 2001 alone.

In the early 1980’s, when only 13 percent of women in the U.S. were getting mammograms, the average tumor size at detection was about 3cm. By the late 1990’s,

when 60 percent were getting mammograms, the average detected tumor size was

2cm. For many women, early detection also means the option of breast conserving

surgery, instead of a mastectomy.

Mortality rates have also declined in the U.S. in the past decade. Some argue that

lowered mortality rates for breast cancer may be attributable to better treatment

options rather than early detection. It is intriguing however, to review data compare

from countries that do and do not have national screening programs. The breast

cancer screening program in Sweden is arguably the most comprehensive in the

world. Denmark, Sweden’s Scandinavian neighbor to the South, does not have a

screening program. Germany also does not have a comprehensive screening program

and never has. The U.S. has a growing program of mammography screening, with

Medicare and Medicaid coverage, CDC programs, and private insurers.

The incidence of breast cancer per 100,000 population is lower in Germany than

in the Sweden; lower in Denmark than in the U.S. Nonetheless, the ratio of mortality to incidence rate (which approximates the percentage of people who will die from

the disease) is far lower in Sweden (22 percent) and the U.S. (23 percent) compared

to Germany (32 percent) and Denmark (36 percent).

Country Incidence Mortality Ratio

Sweden .................................................................................................................... 81.03 17.48 22%

United States .......................................................................................................... 91.39 21.22 26%

Germany .................................................................................................................. 73.65 23.74 32%

Denmark .................................................................................................................. 86.15 29.16 36%

Further, the rate of mortality decline in Germany and Denmark have not kept

pace with the declines in the U.S. Between 1990 and 1996 (the last year of data

for all four countries), breast cancer mortality declined 12 percent in the U.S. and

8 percent in Sweden, compared to 1 percent in Denmark and Germany.

Country 1990 1996 %change

Denmark .................................................................................................................. 26.88 27.25 ¥1%

Germany .................................................................................................................. 21.87 22.03 ¥1%

Sweden .................................................................................................................... 17.80 16.39 8%

United States .......................................................................................................... 22.54 19.75 12%

Dr. Gabriel Hortobagyi, of M.D. Anderson, believes that both early diagnosis and

treatment play an important role in the decrease, stating, ‘‘The available data would

indicate that early diagnosis would reduce risk of mortality by about 25–30 percent

and that optimal adjuvant chemotherapy plus hormonal therapy would reduce risk

of mortality by about 30–45 percent. However, neither approach has been applied

to its full potential—not every woman between ages 40 and 65 has annual mammograms, and not everybody with primary breast cancer larger than 1cm receives optimal adjuvant systemic therapy.’’ It is interesting to consider therefore, that the decrease in mortality observed in the U.S. may be only a fraction of the decrease one

would observe, were both early detection and optimal timely treatment be available

to all eligible women.

The Komen Foundation appreciates the significant role economics play in screening, and that new interventions must also be cost-effective. However, we cannot

align ourselves with a ‘‘bottom line’’ philosophy, as therein the cheapest patient is

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a dead patient. Thus, while we consider all screening and treatment with an eye

toward cost-effectiveness, the Komen Foundation still puts faith in a procedure that

yes, holds elements of uncertainty, but also holds proof of lives saved.

There are unanswered questions, not only behind mammography, but also behind

its debate. What has really spurred this vigorous deliberation yet again? If the opponents of mammography vehemently deny substantial benefits, arguing instead that

the risks tip the scales unfavorably, why then is there no call for a national ‘‘cease

and desist’’ for all screening?

There is always a role for economics, but if that’s the heart of this debate, then

lay it on the table and have it examined objectively. If there’s an argument for

spending public and private dollars on research rather than screening, then it too

should be aired for public examination.

To truly eradicate breast cancer, we must not only meet the immediate needs of

women facing this disease today, but we must also invest in research for future generations. This is how grants are made at Komen—investing in tomorrow and today.

But even then, the fight is not won. The greatest tragedy would be to discover that

elusive cure or prevention and not be able to get it into the hands of each and every

person who needs it, regardless of where they live or their ability to pay.

Clearly, the issues of risk and economics need to be spoken in a language women

will understand. And for that, we encourage the members of these two committees

to review this issue carefully to resolve the unanswered questions and confusion

surrounding the risks of mammography. It is too hard to argue that a decrease in

deaths of American women due to breast cancer is not related to a link in awareness

and its sister messages of early detection and annual screening.

Women are in a quandary. Will you send the message to your mothers, sisters,

aunts, wives and daughters to wait for a lump to be felt to find their breast cancer,

even when we are able to find it much earlier? Public Health is in a quandary. Will

even low-cost, effective screening methods be disallowed in a time of tightened

healthcare budgets? And researchers are in a quandary. Will their years of research

be allowed to go fallow due to politically motivated debate?

Rather, let us allow ‘‘steadfast hearts’’ and ‘‘large minds’’ to rule the day, and advocate instead for the recommendation of the U.S. Preventative Services Task Force:

take advantage of the only widely available screening tool we currently have proven

to find breast cancers before they grow to the size that can be felt by hand. The

ACS sees no reason to change its screening recommendation. The NCI declares that

the evidence will not support a change in their recommendations. We at the Komen

Foundation will remain true to ours as well. Thank you for this opportunity to appear before you today.

Senator MIKULSKI. Thank you very much.

Senator Clinton, I am happy to do the wrap-up questions; if you

want to go first and lead off this round, we are happy to have you

do so.

Senator CLINTON. Thank you very much.

I want to thank the panelists. We have three extremely dedicated witnesses who have given their lives to this fight against

breast cancer.

I could not agree more with the point that Fran Visco made

about the inequitable distribution of resources with respect to dealing with breast cancer. In fact, most of our major health problems

are more likely to fall disproportionately on the poor, on the people

who do not have access to affordable, quality, reliable health insurance. I think that the National Breast Cancer Coalition’s constant

advocacy on behalf of more resources and better access has been an

extremely important part of this debate, and I hope that it is not

a point that is going to be forgotten, because we still have a lot of

work to do.

I want to ask Fran about what the Coalition’s current review of

insurance coverage with respect to not only mammography but to

breast cancer treatment in general has led you to conclude about

any action that we need to be contemplating with respect to insurance coverage.

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Ms. VISCO. I think one of the most important issues before the

Congress now is coverage for oral anti-cancer drugs. As you know,

breast cancer is primarily a disease of older women. Medicare does

not cover tamoxifen, which is probably responsible for much of the

decrease in mortality that you have seen in the charts that Dr. von

Eschenbach put up. That is a critically important question in

breast cancer, much more important than if a woman has to wait

3 months for a screening mammogram.

I also want to say that there is no way that the National Breast

Cancer Coalition would let up on pushing for access to health care

for all women and all Americans.

Another point that I need to have the opportunity to make is

about breast self-exam. There is no scientific evidence that breast

self-exams save lives. That is another infrastructure that has been

built up in this country based on no evidence, and in fact the evidence that we are seeing now indicates that there may not be a difference in mortality through teaching breast self-exam.

Senator CLINTON. Thank you.

Dr. Runowicz, I really appreciate your perspective, both as a physician and as a breast cancer survivor yourself. What is the best

way for us to dispel the confusion and to some extent even more

than that, the despair that women feel about knowing what they

are supposed to do and who they can believe and how they make

the decisions. I think that what the American Cancer Society and

the National Cancer Institute and others have said, which is, I

think, putting it sort of simply, that you cannot let the perfect be

the enemy of the good, and until we know something more than we

know now, it is prudent to continue to recommend the same standards that we have adopted.

How do we get that message out?

Dr. RUNOWICZ. I think that is a very big challenge, and one article on the front page of The New York Times can undo all the good

of all of the organizations. But I think that hammering home the

same consistent message and letting patients know that controversy is what science is all about, and that is how we make new

discoveries, but until we have other data that make us change

these guidelines, these guidelines are based on good science, and

we need to get that message out over and over again.

Senator CLINTON. I thank you for your role in doing that.

And Dr. Leffall, thank you for your years of service to patients

and as an advocate and spokesman. From your perspective also

dealing with patients and from the Komen Foundation work that

you do, is there more that we could do in the Congress to try to

convey more support for the clinicians’ work that you and Dr.

Runowicz and others are doing? How can we help you get the message out, and from your perspective, what additional steps should

we be taking in funding to try to move the breast cancer debate

beyond mammography to prevention and cure and some of the

other issues that are at the root of it?

Dr. LEFFALL. We must always be concerned about those, Senator

Clinton, prevention and cure. But one thing that I think you can

do—so many of my colleagues who are radiologists are now telling

me that they are no longer willing to perform mammography because the reimbursement they receive is not worth it from a pragVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00084 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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matic point of view. They say, ‘‘I want to help patients’’—that is

why we are in medicine, to help patients—‘‘and I do not get enough

to pay the expense in my office.’’ So that is something that certainly can be done, but in addition

to that, as long as we can continue to emphasize that until we have

something better, the things that are based on science—and the

mammography recommendations are based on scientific data—and

we are not opposed to other people looking at those data to be sure

that they are what they say they are, and if there is a difference

of opinion, let us talk about it; let us not try to hide it. But that

is something that we can do for the radiologists who perform mammography.

Senator CLINTON. Thank you, because as I said earlier, that is

a big problem in New York and is becoming a real barrier to access, so that even if women are presented with all sides of this

issue and make the determination that they want a mammogram,

it is becoming harder to get one, either because of access or affordability.

Dr. LEFFALL. That is correct.

Senator CLINTON. I want to again thank Chairman Mikulski for

holding this important hearing along with Chairman Harkin. It

was a very important service.

Senator MIKULSKI. Thank you very much.

Senator Harkin?

Senator HARKIN. Thank you very much, Madam Chairman.

Dr. Leffall, regarding one point you just mentioned, I just want

to say that I do have a bill in to increase that reimbursement rate

for radiologists. I have been hearing from them, and just yesterday

in Iowa the question was asked as to what does a mammogram

cost. They said $100 to $120, somewhere in that range. I think the

reimbursement is now around $75; is that right?

Dr. LEFFALL. Average.

Senator HARKIN. Average about $75?

Dr. LEFFALL. Yes.

Senator HARKIN. So you are right—a lot of people are just turning people away.

Dr. LEFFALL. They are not doing it anymore; that is correct, Senator.

Senator HARKIN. So I do have a bill in to get the reimbursement

raised, and if I can find something to attach it to this year, I will

attach it.

Dr. LEFFALL. Very well.

Senator HARKIN. I am wondering, though, if I will get comments

on the floor that maybe this is not necessary. I don’t know. Is it

necessary? With the confusion that seems to be out there now, people will say, ‘‘Why do you want to increase the reimbursement rate

to radiologists who do mammograms when we do not even know if

mammograms are effective? Maybe we should not do it.’’

Dr. LEFFALL. But most groups in the United States believe that

until we get something better, this is what we should continue to

recommend. That is why the Komen Foundation is recommending

it, ACOG, NCI, the American Cancer Society—because we believe

that it is based on the available science that we have today. And

we would like to emphasize that we are not opposed to a re-look

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at the data to be sure that it is what we say it is, and let patients

know the truth. We are not trying to hide the truth. But when you

come up with something better—and Dr. von Eschenbach mentioned some things like the PET scan, MRI, digital mammography—when they prove to better, we can go to that, but until

then, I think we should stick with what we have that we know can

make the diagnosis early. And you have asked many questions

today about early detection, which is extremely important.

Senator HARKIN. Fran Visco, we have worked together now for

over 10 years.

Ms. VISCO. Yes, that is right.

Senator HARKIN. You said in your testimony that we have got to

ask if mammography screening is the best use of finite dollars.

Well, if not, then, what do we do?

Ms. VISCO. Well, I think we should use them to give health coverage to women. I think that women need to be reimbursed for

their medicine. I think that more women need to have access to

quality care. There are many areas that are looking at truly early

detection, looking at how to prevent breast cancer, looking at

nontoxic targeted therapies.

The mammography debate is sucking up all of our time, all of

our dollars, all of our attention, all of our focus. There is so much

more to eradicating breast cancer, and that is where we need to

move those dollars.

Senator HARKIN. How much do we spend yearly on mammography?

Ms. VISCO. It is a multibillion-dollar number; exactly how many

billions, I do not know. I have seen numbers recently, but they are

not in my head; I know that it was many billions.

Senator HARKIN. Are most covered by insurance and Medicare—

mostly Medicare?

Ms. VISCO. Probably. I do not know the answer to that question.

Senator HARKIN. I would like to find that out.

Senator MIKULSKI. But not for the poor. Senator, just in the interest of a little dialogue, you have Medicare covering mammography, but that is every other year—but at least it is something,

and we spearheaded that. Then, those of us who have private insurance receive reimbursement, but again, you have got to watch

your time on that, or they will not cover that. But for poor women,

the only thing that we have is the breast and cervical screening

program at CDC, which the women of Congress initiated and, Senator, you have been steadfast in helping provide the funds for it.

Did you hear what I just said? [Laughter.]

Senator HARKIN. I am sorry. Everybody is talking to me at one

time.

Senator MIKULSKI. I said that for reimbursement, Medicare provides it for the women over 65 every other year; for other women,

it is reimbursed through private health insurance, and again, it

has age guidelines; third, for poor women, the only tool—and it is

a down-payment tool—is for the breast and cervical cancer screening at CDC, and that is funded through—— Ms. VISCO. The treatment component that we worked on for 4

years and last year, we were finally successful in getting enacted

into law, where women who are screened through the CDC proVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00086 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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gram, once they are diagnosed, become Medicaid-eligible for their

treatment.

Senator MIKULSKI. That is right. But you fund in Labor-HHS the

CDC program; but if it were not for your funding in the CDC program, poor women would not even have an option—and by and

large, even there, it is still a rather spartan number of women who

can participate. But even when they are screened, the Medicaid is

also an option to the State.

Ms. VISCO. It is an optional program with the States, but the National Breast Cancer Coalition has been very successful over the

past year in getting 39 States so far to opt in.

Senator MIKULSKI. Bravo, bravo for that.

Ms. VISCO. Thank you.

Senator MIKULSKI. But again, for poor women—you see.

Senator HARKIN. My staff tells me the amount spent on mammograms yearly is $3 billion. I assume that it is all covered by insurance and Medicare. So it is a sizeable sum of money. We are up

to $800 million into research now; right?

Ms. VISCO. Yes.

Senator HARKIN. We finance $800 million for breast cancer research. So it is a lot of money for mammography.

Ms. VISCO. And remember, access to health care, too, for these

women to treatment and to oral anti-cancer drugs—very important

issues in breast cancer.

Senator HARKIN. Well, again, we’re trying to clear this up and

trying to get a definitive answer to women out there. What would

you tell my nieces? Both of their mothers died of breast cancer.

They are now in their late 30’s now, maybe almost 40, and they

have been getting breast cancer screening because of that. What

would you tell them?

Ms. VISCO. I would tell them to go to the National Breast Cancer

Coalition website and look at our question-and-answer, which lays

out all of the issues on this very debate, and we would be happy

to help them work their way through it, and then they can make

up their minds about what they want to do. But I think women

have the power and the capability to understand this complexity

and to make a decision on what to do.

Senator HARKIN. I believe that is true also, but I think early detection right now is still the best.

Ms. VISCO. We may not know how to detect breast cancer early

enough.

Senator HARKIN. I know that. I read that in your testimony.

Ms. VISCO. Believe me, I wish——

Senator HARKIN. And we are working on the blood test, as we did

for ovarian cancer. That might be possible for breast cancer. They

are working on it now. But in the meantime we do not have it. It

might not be early enough, but finding it with mammography is

earlier than detecting it during a physical exam.

Ms. VISCO. But the issue is does it make a difference, and that

is the debate around the trials.

Senator HARKIN. I thought the answer to that was, all other

things being equal, yes, it makes a difference. The earlier you detect it, the better the quality of life and the higher probability of

having a longer life.

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Ms. VISCO. Let me respond that the data do not necessarily show

that in terms of length of life, but certainly quality of life. The data

from the trials show that more mastectomies are performed in the

group that is screened by mammography than in the control group,

because we do not know how to treat very early breast cancer, and

we tend to do mastectomies often in that population.

Senator HARKIN. Or lumpectomies, or something like that.

Ms. VISCO. Yes, but the data show that more mastectomies are

done in the mammography screened group. That is the data.

Senator HARKIN. But that data from the sixties, seventies and

eighties.

Senator MIKULSKI. And now we have new approaches.

Senator HARKIN. Yes, we have new approaches now. That is why

I keep saying the Danish study does not take into account some of

the new technologies and new interventions that we use now.

Ms. VISCO. OK. I know we can have this debate forever, and

again, I believe that our Q and A lays out some of these issues, and

perhaps it warrants a longer debate at another time. But sometimes breast cancer is not a very logical disease; it is a very complex disease.

Senator HARKIN. Well again I ask, as I asked the other panelists:

all things being equal, if someone has the insurance coverage or if

they are low-income and can get access to the breast and cervical

cancer screening program, should they go ahead and have a mammogram?

Every single person I talked to yesterday in my State of Iowa answered yes. These were clinicians, doctors, nurses, and breast cancer survivors. Every single one said yes. I am not a doctor and I

would not give advice, but I think one of the purposes of our hearing is to try to clear the air a little and get a little more clarity

for the women of this country.

You are right, women can make up their own minds—— Ms. VISCO. Yes.

Senator HARKIN [continuing]. But it is very difficult to make up

your mind when you are faced with a life-threatening illness, and

the people in whom you put your trust and confidence do not have

definitive answers or clear guidelines for you.

I keep coming back to my basic question: all other things being

equal, is early detection better than later detection, and will mammography give you earlier detection?

Dr. Runowicz, what do you say?

Dr. RUNOWICZ. I would like to answer several of the questions

that you have raised. On your nieces, there has been a breast cancer prevention trial that has been completed in this country and

showed that tamoxifen prevented breast cancer, and there is the

STAR study now. If they meet the eligibility criteria—and I do not

think they will because they are not postmenopausal—but I would

certainly encourage that they look into clinical trials and that they

certainly discuss the issue of tamoxifen.

As far as right now, there is no compelling evidence to alter any

of our guidelines. Every, single major institution, every, single

major organization, is still saying ‘‘Stick with your guidelines,’’ which are from age 40 to 50 every one to 2 years—some organizations are every year, such as the American Cancer Society; others

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are every one to two, such as the National Cancer Institute, and

the American College of Ob-Gyn—after 50, every year until there

is another comorbid condition which precludes the sensibility of

continuing mammography.

The debate here today is a statistical debate. The debate here

today is media hype. The debate here today is The New York

Times front page. That is why we are here today. We are not here

because there is new data. We are here because there are statisticians who, in their own group, the Cochrane group, which is an excellent group—these two investigators did not have the entire

group behind them, and the Lancet article that they published was

not published with the entire backing of that group. Instead, that

group published a separate article, and they have their website,

where dissension from the two authors.

That is why we are here today—because somebody has reanalyzed data, and they have chosen, based on their statistical evaluation, that they wish to exclude other studies, to which other groups

like the U.S. Preventive Services Health Task Force said no, we do

not agree with their exclusions.

So looking at the raw data again—and it has been done in

1993—but looking at that raw data again will perhaps readdress

these issues. But there is no compelling evidence, there is no new

evidence, to alter our guidelines.

Was that clear?

Senator HARKIN. That is very clear.

Dr. LEFFALL. Senator, I would just like to echo—you asked the

question about your nieces—without any question, I believe the answer is yes, please get the screening mammogram. And this is not

saying you are opposed to any of the other things that have been

mentioned today in terms of access to care. What could be more important than access to health care? It is one of the most important

things. But today we are talking about the mammography debate,

and it is a debate, a statistical debate.

But I think Dr. Frist, a colleague, mentioned it. When you are

sitting with a patient, and that patient—once again, you go with

a lot of information—they say, ‘‘You are asking me to make a decision in a few minutes, and you have spent your entire professional

life studying this. I do not think you are being fair to me.’’ I would

get that when I used to go into a lot of detail; yet you try to inform

patients. Patients should be informed. Patients are very intelligent.

They should be informed. But when we cut through the chaff to get

to the wheat—get the screening mammogram—that is the answer.

Senator HARKIN. Thank you all very much. I appreciate it.

Senator MIKULSKI. Before we conclude—because I said I would

be the wrap-up questioner—I just want to reiterate essentially

what has come out of this hearing and then have a final question

for you, Doctor.

First of all, what we see is that the biostatisticians disagree.

That is clear. And they will continue to look at data and analyze

it.

Clinicians, those who have the lives of patients in their hands,

do not disagree that clinicians agree and recommend in the most

enthusiastic, unabashed, and unqualified way that we follow the

existing guidelines that have been established by the National CanVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00089 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
86

cer Institute, recently reaffirmed by the Preventive Services Task

Force at HHS, and have also been the longstanding recommendations of the American Cancer Society.

So this hearing should not end without it being clear that those

who are in charge of America’s public health, its research institutes, the oldest cancer organization in the United States of America, and representing the clinicians all agree that if you are 40 or

older, you should have a mammogram every other year, and if

there is indication of greater risk, either genetically or because of

medications, to pursue it.

That is where there is agreement. There is also agreement,

whether it is among the biostatisticians or among the advocacy

groups, where again there is disagreement.

But first of all, yes, we need access. We need access to women’s

health care. And as part of that, if you have access to health care,

your doctor can then recommend what are the best next steps. It

could be diabetes; it could be lung cancer, which is the biggest killer of women; it could be heart disease, etc. But we need access to

health care, and then, access also to treatments, which means the

way we need to look at our patients’ bill of rights. I believe, Doctor,

that ob-gyns should be designated also as primary care providers.

You are the first and sometimes the only physician that women

see, and you are the one who can say, ‘‘Wow, 20 years on birth control—we had better get you in now, even though you are 38 years

old.’’ So access is important.

Of course, this debate is moot for the poor because of limited access to health care and the even further limited nature of access

to treatments, even where there is diagnosis. We have all heard

that.

I thank all of you for mentioning the mammogram quality standards as well as the Cervical and Breast Screening Act at CDC.

Thanks to the advocacy groups, and Fran, I particularly want to

mention your group. We really pushed for that. I take pride that

I was one of the prime movers of that initially, and then we had

these fine men of the Senate really support us. We now know that

it has made a difference, and we welcome any views on the mammogram quality standards, so we thank you for that.

So that is where we agree. We agree that we have got to have

our mammogram quality standards. We agree that we need research on new tools and on new treatments—but new tools and

new treatments are a hollow opportunity if we do not have access

to health care for women, and the start for what is the best way

to go for whatever we confront really needs to start with access to

health care.

So that, then, is where I think we agree, and I think if people

ask me, ‘‘What do you think about all this, Senator?’’ I would say

that we need to stay the course in terms of the existing guidelines

until there is clear, compelling, and convincing evidence otherwise.

We really need to pursue these mammogram quality standards as

well as new research.

I am going to close with the access issue. I have raised this issue,

as have Senator Clinton and others. We have got to be really careful that while we scientifically disagree, we do not end up discouraging health insurance plans from covering this important screenVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00090 Fmt 6633 Sfmt 6601 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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ing tool. It might not be the best tool right now, although it seems

to be the only reliable, or at least pretty reliable, tool. In fact, we

would like the health insurance industry to take a whole new,

fresh look at women’s health care and what they reimburse, starting with designating the ob-gyn as the primary care physician,

along with other internists.

So we say to the insurance companies that we hope you have

learned something, and we say most of all to American women that

if you are over 40, get a mammogram; if you are under 40, let us

find a way to get you in to talk to someone to see if you are at risk

and go from there.

Thank you very much. I really want to thank everyone who presented their views today, and to the biostatisticians, thank you

even for your disputed presentations, because they have caused us

now to take a new look at where we are. So we thank you, and we

encourage you to continue in your own good work.

This hearing stands adjourned.

[Additional material follows:]

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1 .abMiettinen OS, Henschke CI, Pasmantier MW, Smith JP, Libby DM, Yankelevitz DF.

Mammographic screening: no reliable supporting evidence? Lancet 2002;358:404–06. 2 .abMiettinen OS, Henschke CI, Pasmantier MW, Smith JP, Libby DM, Yankelevitz DF.

Mammographic screening: no reliable supporting evidence? BMl1lwww.theLancet.com. 3 .abLetter to the editor. Lancet 2002, Feb 23. In press.

ADDITIONAL MATERIAL

PREPARED STATEMENT OF CLAUDIA I. HENSCHKE, PHD, M.D.

Our testimony on behalf of mammography screening is based on our recent article

published in The Lancet on February 2, 2002 123. We there responded to the publication by Olsen and Gotzsche (also published in The Lancet, October 20, 2001) in

which they concluded that of the seven major mammography studies, five were severely biased and thus could not be used to evaluate mammography. They stated

that neither of the remaining two (Malmo and Canadian) studies considered to be

acceptable showed a benefit.

In our paper, we focused on the Malmo and Canadian studies that Olsen and

Gotzsche deemed acceptable to illustrate that they, among many others, ignored

larger and even more fundamental flaws in their analyses and that this lack of understanding led them to produce misleading, falsely nihilistic evidence. These fundamental flaws are inherent in the currently prevailing approach to assessment of

any screening test for cancer: the failure to continue screening long enough in a

study for its benefit to become evident and the failure to assess that resulting benefit, namely the reduction of cancer deaths, during a relevant time period, that is,

sufficient distant from the onset of the screening program. If the approach is flawed,

conclusions drawn from such an evaluation will also be flawed.

We showed that in the Malmo study, mammography provided for a 55% reduction

in the breast-cancer case-fatality rate in women 55 years and older and about a 30%

reduction in those aged 45 to 54. This benefit, however, only became evident after

six years of screening, that is from the seventh year of screening onward. It was

only in the Malmo study that screening was not discontinued prematurely as had

been done in the Canadian study.

It should be self evident that when a screening test picks up a cancer and this

cancer is cured by the early intervention provided by the early detection, the death

that would have otherwise occurred in the absence of screening would have been

at some point in the future, typically years later. The better the screening test, the

earlier the detection, the longer the time required before the evidence of the benefit

becomes apparent. Thus, when assessing the screening benefit, screening must continue for sufficiently long to recognize the deaths which were prevented in the

screened group as compared to the control group. Many studies have been done to

evaluate mammography, yet we still are left in a state of confusion. This situation

should not be repeated with screening for other cancers. Thus, we endorse these

public hearings, but plead that before anything else, the fundamentals of research

on screening for cancer be re-examined in open discussions. Some current examples

of the now prevailing flawed approach are worth noting.

The National Cancer Institute (NCI) is about to embark on a new trial to evaluate

spiral CT for lung cancer. This study will cost approximately $300 million (approximately the same amount the U.S. is planning to spend on rebuilding Afghanistan),

will last 10 years, and its current design exhibits the same fundamental flaws that

we have addressed. The ongoing PLCO (Prostate, Lung, Colon, Ovary) screening

study currently underway, started in 1993 and projected to last until 2014, is the

most expensive screening study ever performed by NCI until the recently contemplated spiral CT study. The PLCO costs approximately $150 million. It similarly

ignores the fundamental principles we addressed. We therefore expect both of these

studies to yield misleading results. In addition, these studies take so many years

to complete that the screening they seek to evaluate may well be obsolete by the

time the study is completed. For example, the lung component of the PLCO will

evaluate the chest x-ray screening for lung cancer. In 1993 this may have been a

reasonable consideration; by 1999, it was clear that spiral CT was far superior in

detecting early lung cancer, and by 2014, even spiral CT likely will be outdated.

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UPMC HEALTH SYSTEM,

PITTSBURGH, PA 15213–3180,

February 21, 2002.

Hon. ARLEN SPECTER,

U.S. Senate,

Washington, D.C. 20510.

DEAR SENATOR SPECTER: I am the Director of the Breast Program at the MageeWomens Hospital/University of Pittsburgh Cancer Institute and the protocol chairman for the National Surgical Adjuvant Breast and Bowel Project STAR trial, the

Study of Tamoxifen and Raloxifene that is funded by the National Cancer Institute.

I understand that on February 28 you will be participating in a Labor, Health and

Human Services and Education Appropriations Subcommittee and the Health, Education, Labor and Pensions Public Health Subcommittee joint hearing on mammography. As you prepare for this hearing, I wanted to bring to your attention another

important weapon in our battle against breast cancer—breast cancer risk assessment.

While the debate over mammography is critically important, the statistics show

that mammography alone is not enough. In addition to mammography and other

tools for early detection, attention also needs to be focused on prediction and prevention—identifying those women who are at highest risk for breast cancer, and intervening to prevent them from developing breast cancer in the first place. Fortunately, women at high-risk now have several ways to reduce their risk and help prevent breast cancer. However, these options all involve difficult risk/benefit decisions,

which heightens the importance of better predicting which women are most likely

to benefit from early, preventative intervention.

One approach to refining our predictive abilities is to move risk assessment from

statistics to science. Along with evaluating a woman’s family history, age and other

general risk factors, we now have biologically-based risk assessment tools to consider. For example, ductal lavage is a procedure in which the cells lining the milk

ducts are collected and analyzed under a microscope to determine whether they are

abnormal. Published studies demonstrate that high-risk women with atypical milk

duct cells have a significantly increased, near-term risk of developing breast cancer.

Using such individualized risk information, we can identify women at very high risk

for breast cancer and better target our ability to offer them risk reduction options.

Because of my commitment to encouraging the routine practice of risk assessment

among breast care specialists, I am currently serving as the chair of the Risk Assessment Working Group (RAWG), which consists of 13 leading breast specialists.

On February 27, 2002, members of the RAWG will participate in the first risk assessment symposium of its kind at the 19th Annual Miami Breast Cancer Conference. At the conference, we will be presenting a consensus Risk Management

Strategy, which will help guide breast specialists in the practice of risk assessment

and the management of high-risk women. I have attached copies of two posters on

breast cancer risk assessment and ductal lavage that will be presented at the Miami

conference. Following the conference, the RAWG plans to broadly distribute the

guidelines to the breast health community and pursue publication in a peer-reviewed journal.

As more prevention options become available for women at high risk of breast

cancer, individualized risk assessment becomes increasingly important. I would like

to stress, however, that neither risk assessment nor ductal lavage are substitutes

for breast cancer screening. Rather, they are intended to serve as adjuncts to mammography and breast physical examinations. Early detection and preventative measures are both critical to our fight against breast cancer.

I hope that you will submit my letter to the record, so that you can share this

important information about breast cancer risk assessment with your colleagues.

Please feel free to call me at (412) 641–6500 if you have any questions or if I may

be of further assistance to you or your staff. Thank you for your leadership on this

and other important women’s health issues.

Sincerely yours,

VICTOR G. VOGEL, MD, MHS, FACP,

Professor of Medicine and Epidemiology,

Director, Magee/UPCI Breast Program.

PREPARED STATEMENT OF THE AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

The Agency for Healthcare Research and Quality (AHRQ) respectfully submits the

following testimony on the effectiveness of screening mammography for the record.

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Today’s hearing is very timely in light of the recommendation from the U.S. Preventive Services Task Force (USPSTF) released last week on February 21, 2002, by

HHS Secretary Tommy G. Thompson. The USPSTF is a leading independent panel

of private-sector experts in prevention and primary care sponsored by AHRQ that

conducts rigorous, impartial assessments of scientific evidence for a broad range of

preventive services. In its new recommendation, the USPSTF endorsed screening

mammography every 1–2 years for women ages 40 and over.

AHRQ’s mission is to support research designed to improve the outcomes and

quality of health care, reduce its costs, address patient safety and medical errors,

and broaden access to effective services. The research sponsored, conducted, and disseminated by AHRQ provides information that helps people make better decisions

about health care.

With this mission, AHRQ-funded research activities provide meaningful, evidencebased information on screening mammography to women and their clinicians. The

Agency does this in three ways: first, supporting research that informs the quality

of mammography and interpretation of mammograms; second, supporting a review

of the up-to-date evidence on mammography screening by the U.S. Preventive Services Task Force (USPSTF); and third, developing evidence-based materials for patients and clinicians.

QUALITY MAMMOGRAMS

Screening mammography is an important tool for reducing deaths from breast

cancer in women 40 and older. However, it is not a perfect tool. Because it is not

as specific a test as it could be, false positives can occur which often require repeat

screening and/or biopsies. This can cause significant anxiety among patients and

their families, as well as unnecessary health care expenditures. In addition, problems with mammogram interpretation and communication of results to patients can

result in cancers that are missed and treatment that is delayed.

As a result, the effectiveness and usefulness of mammography have been the subject of controversy for many years. AHRQ, along with other agencies of the Department of Health and Human Services, have worked to build the foundation of evidence for the effectiveness of mammography and to ensure that patients have access

to high quality screening.

One of AHRQ’s earliest activities in this area was the development of a clinical

practice guideline on how to identify the elements of high quality mammography

screening.

The guideline, developed in 1994 by an independent panel sponsored by AHRQ’s

predecessor, the Agency for Health Care Policy and Research, was entitled Quality

Determinants of Mammography. The multidisciplinary panel that developed the

guideline comprised radiologists, radiologic technologists, medical physicists, family

practice physicians, a nurse, an obstetrician-gynecologist, a surgeon, a pathologist,

an internist/oncologist, and consumer representatives. Many of these panel members

also served on the original Food and Drug Administration (FDA) National Mammography Quality Assurance Advisory Committee.

The guideline provided information to clinicians on providing high quality mammography services and also gave patients information on how to determine the quality of the mammography services they received.

It is important to note that science and research are continually moving forward,

and that medical practice must keep pace. In 2001, AHRQ reviewed the guidelines

it had developed in the 1990s to determine which were still scientifically valid.

Among those found to be out of date was the Quality Determinants of Mammography, a guideline that was published in 1994 and is therefore 8 years old.

Given the restructuring of AHRQ’s guideline development activities in 1996, the

evidence base for the guideline has not been updated since its initial release. A recent study sponsored by AHRQ has shown that the lifetime of a guideline is variable, but, generally, guidelines should be reviewed every 3 years

AHRQ now makes evidence-based guidelines available through the National

Guideline ClearinghouseΤΜ (NGC), an Internet-based compendium of more than

1,000 evidence-based clinical practice guidelines found at http://www.guideline.gov.

At this time, the site contains 76 guidelines related to breast cancer and 23 related

to mammography. AHRQ sponsors the NGC in partnership with the American Medical Association and the American Association of Health Plans. The NGC Web site

provides the most current recommendations on screening mammography from leading guideline developers in the United States and around the world.

The NGC is an internationally recognized source of high-quality, evidence-based

clinical information. Currently, NGC has approximately 55,000 user sessions and

950,000 hits a week. Guideline developers are contacted yearly to verify that their

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guidelines are considered current. After 5 years, if the developer has not reviewed

its guideline, it is withdrawn from the site.

RESEARCH ON MAMMOGRAPHY

AHRQ sponsors health services research that helps to inform the delivery and

quality of health care services. The Agency has supported a number of important

studies on the quality of mammography, its interpretation, and access to screening.

A study by Craig Beam, Ph.D., of the Medical College of Virginia, found that U.S.

radiologists looking at the same mammogram are likely to interpret it quite differently. In their study sample, Dr. Beam and his colleagues found that some radiologists referred 100 percent of women with cancer for biopsy, while others referred

only 47 percent. Inaccuracy in mammogram interpretation may mean that breast

cancer goes undetected or is detected at a later stage, when it is more difficult to

treat successfully.

Another AHRQ study, co-funded with the National Institutes of Health, is attempting to identify reasons for variability in the interpretation of mammograms.

The study, led by Joann Elmore, M.D., at the University of Washington, is a unique

collaboration among three geographically distinct breast cancer surveillance programs in the states of Washington, New Hampshire, and Colorado. This collaboration will permit the collection of breast cancer outcome and interpretive data on

more than 500,000 mammograms from 91 facilities and 279 radiologists.

Dr. Elmore’s study is especially timely because it takes place in the community

setting where the majority of mammograms occur. Although mammography facilities are subject to rigorous accreditation standards regulated by the FDA, requirements do not include an evaluation of radiologists’ accuracy levels in mammography

or address the issue of variability in interpretation. Identifying the causes of variability of interpretation will be extremely important in enhancing the quality of

screening mammography.

The Agency also is supporting research to understand barriers to breast cancer

screening and improve access. For example, a study funded by AHRQ found that

negative attitudes about mammography might play a role in the disproportionate

number of breast cancer deaths among African American women compared with

white women. Knowledge of screening recommendations and access to free mammograms were not enough to get some low-income black women to keep their mammography appointments. Most of the women who skipped their appointments said

they were embarrassed or believed that a mammogram was unnecessary if they

didn’t have any symptoms.

Another study funded by AHRQ found that a major reason women cite for not undergoing breast and cervical cancer screening is that their physicians never recommend it. Older women, in particular, are less likely to be screened. This may be

due in part to conflicting professional recommendations for screening older women,

the many competing causes of mortality as women age, and possible negative attitudes about screening held by doctors and their older female patients.

An important element of AHRQ’s research agenda is helping to ensure that the

research it sponsors is translated into improved clinical practice. The first step in

this translation is the publication of these findings in the professional literature.

The Agency also works with professional and patient groups to disseminate the findings to those who can put them to work in routine medical practice.

NEW USPSTF MAMMOGRAPHY RECOMMENDATION

The debate over the usefulness of mammography has recently intensified. Much

of this debate has focused on the critiques of the scientific literature on mammography screening by Olsen and Gotzche of the Nordic Cochrane Center in Copenhagen.

Over the last two years, the USPSTF has been reviewing the same scientific literature. The findings from this review were the foundation of the mammography

recommendations released by Secretary Thompson on February 21.

Acknowledging that the scientific evidence is not perfect, but not as flawed as others have claimed, the USPSTF recommends screening mammography every 1 to 2

years for women age 40 and older. Evidence of benefit and reduced mortality is

strongest for women aged 50–69, the age group generally included in screening

trials.

The evidence was unclear on when women should have their first mammogram

and how frequently they should be screened, so the Task Force recommends that

women should discuss their personal preferences and the harms and benefits of

mammography with their clinicians to determine when to start routine screening

mammography and the optimal interval for screening.

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AHRQ is working to get the new USPSTF recommendation translated into improved clinical practice and into information that will help reduce confusion and

anxiety among patients.

As a start, AHRQ has made the new recommendation on mammography available

on our Web site at http://www.ahrq.gov/clinic/3rduspstf/breastcancer/index.html.

Also available are a fact sheet for clinicians and information for patients.

AHRQ also will use the Put Prevention Into Practice (PPIP) program to help get

this information out to preventive services providers and patients around the country. PPIP, an AHRQ program, is designed to increase the appropriate use of clinical

preventive services, such as screening tests, immunizations, and counseling, which

are based on USPSTF recommendations.

CONCLUSION

AHRQ has a tradition of supporting and conducting evidence-based research and

translating that research into improved clinical practice. The Agency also has led

the way in providing evidence-based information for health care decision making for

mammography, other important screening tools, and other clinical issues.

As HHS Secretary Tommy G. Thompson said on February 21, screening mammography can save lives. But this test is not perfect, and we need more research to improve the mammography and the interpretation of results. We also must ensure

that women have the information they need to make decisions about their own

health. Finally, it is particularly important that we continue periodic evaluations of

the available scientific literature to ensure that medical practice and patient decision making are based on an up-to-date foundation of evidence.

Thank you very much for the opportunity to comment on this important issue,

and we look forward to any questions that you may have.

PREPARED STATEMENT OF THE FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF

HEALTH AND HUMAN SERVICES

INTRODUCTION

Madam Chairwoman, Mr. Chairman, members of the Committees, thank you forgiving the Food and Drug Administration (FDA or the Agency) this opportunity to

present this statement for the record regarding Mammography Quality Standards

Act (MQSA) of 1992.

BACKGROUND

The MQSA of 1992 was enacted in response to serious concerns about the quality

of mammography. This procedure is an aid in combating the mortality associated

with the growing incidence of breast cancer. In spite of the current controversy

about the studies showing the benefits of mammography screening and in the absence of consensus about the scientific issues, the Department of Health and Human

Services (HHS) and FDA support the conclusion reached by the U.S. Preventive

Services Task Force. High quality mammography continues to be the best available

tool for the early detection of breast cancer and MQSA provides our best assurance

of that quality.

Mammography can reveal cancerous lesions up to 2 years before a woman or her

doctor can feel a lump, and is a significant contributor to the current 5-year survival

rate of 86 percent. Mammography represents life-saving ammunition in the war on

breast cancer which is the most common non-skin cancer and, after lung cancer, the

second leading cause of cancer deaths among women.

To achieve these benefits, all elements of the mammography system must be of

high quality. Mammography is a highly challenging radiographic examination of the

breast. The equipment must be capable of producing quality images and be maintained and operated by qualified individuals. Physicians who interpret these images

must also be highly skilled. If the quality of mammography is poor, an incipient cancerous lesion may be missed. False negative diagnoses can delay early treatment

and result in avoidable deaths. Poor quality mammography can also lead to false

positive diagnoses, in which normal tissue is judged to be abnormal, resulting in

needless anxiety for patients, costly additional testing, and unnecessary biopsies.

In the mid-1980s, indications of problems with the quality of mammography

began to appear. Significant evidence came from a 1985 study known as the Nationwide Evaluation of X-ray Trends (NEXT), which was conducted by State radiation

control agencies in cooperation with the FDA. Based on a survey of a representative

national sample of mammography facilities, this study found that the image quality

produced in perhaps as many as one-third of the facilities was less than desirable.

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The findings from the NEXT study catalyzed efforts by the American College of

Radiology (ACR), a private, non-profit association of radiologists, to create a voluntary mammography accreditation program. Begun in 1987, this program included

an evaluation of the quality of clinical mammograms provided by facilities seeking

accreditation. Although it is reasonable to surmise that facilities participating in

this voluntary program were among the better facilities, ACR found that approximately 30 percent of the applicants failed on their first attempt to achieve accreditation.

Other evidence came from a 1990 General Accounting Office (GAO) study that reported that many mammography providers lacked adequate quality assurance programs. In 1992, hearings held by the Senate Committee on Labor and Human Resources revealed a wide range of problems with mammography services in the

United States. These problems included poor quality equipment, lack of quality assurance procedures, poorly trained facility personnel, and inconsistent governmental

oversight. At the same time, several States instituted programs to ensure that their

residents were being provided with high quality mammography.

Despite these efforts, no national standards for providing safe, reliable, and accurate mammography were in place for the over 25 million American women who undergo the procedure annually. To rectify this situation, Congress enacted the MQSA

on October 27, 1992, to ensure uniform high standards for mammography facilities,

their equipment and personnel, and the quality of their mammograms. This law required all mammography facilities be certified by the Federal government after October 1, 1994, except for those facilities operated by the Department of Veterans Affairs (DVA). A separate law mandating a similar program governs DVA facilities.

Responsibility for implementing MQSA was delegated to FDA by the Secretary of

HHS on June 2, 1993.

IMPLEMENTATION

Faced with the task of certifying approximately 10,000 mammography facilities in

less than 2 years, FDA published interim regulations in December 1993, which became effective in February 1994. As a prerequisite to certification, facilities had to

be accredited by an FDA-approved accreditation body, the first of which was ACR

approved in March 1994. Subsequently, four States, Arkansas, California, Iowa, and

Texas, achieved approval as accreditation bodies.

FDA successfully met its demanding statutory deadline of certifying all qualified

mammography facilities by October 1, 1994. While the interim regulations were in

effect, FDA developed more exacting regulations, and the MQSA final regulations

were published in October 1997, and became effective on April 28, 1999.

Another hurdle was obtaining qualified personnel to annually inspect the nearly

10,000 mammography facilities. FDA developed special training courses for both

FDA and State personnel, and trained and eventually deployed 250 inspectors to

conduct annual facility inspections. These inspections began in January 1995. During this time, FDA implemented the Mammography Program Reporting and Information System (MPRIS), a dynamic, interactive data system, designed to tie the

pieces of the program together. MPRIS provides and tracks information on accreditation and certification of facilities, facility inspections, inspection violations, and

the billing of inspection fees. MPRIS also allows inspectors to use uniform software

on a laptop computer while in the field, and to directly upload inspection results

to the headquarters database, thus streamlining the inspection process and facilitating data analysis. In addition, the database transmits daily certification information

to the Centers for Medicare and Medicaid Services, thereby facilitating efficient facility reimbursement, and allowing consumers to search for certified mammography

facilities by zip code.

In order to educate facilities about the regulations and how to comply with them,

FDA published a quarterly newsletter that was mailed to facilities and other interested parties. The printed newsletter eventually evolved into web page updates and

articles on matters of importance to facilities. A mammography website

(www.fda.gov/cdrh/mammography) was created, a principal component of which is

an extensive policy guidance help system.

DEVELOPING PROGRAMS

MQSA allowed States that desired to do so to take on the role of a certifying body,

with FDA approval and oversight. In August 1998, the States as Certifiers (SAC)

pilot was initiated with two participating States. During this time, regulations were

promulgated and published in February 2002. These regulations will become effective in May 2002. Several additional States have expressed interest in the SAC program, and FDA expects this program to expand.

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PROGRAM COMPLIANCE

Compliance with the final regulations continues to improve. Currently, 60 percent

of all certified facilities are in total compliance with MQSA. The Government Performance Results Act goal for most serious violations is less than 3 percent. At this

time, only 2.4 percent of facilities are exceeding the goal. This exemplary compliance

rate can in large part be attributed to the program’s extensive outreach efforts, including facility education by inspectors, and the availability, both on the web and

in hard copy, of all guidance and policy determinations.

PROGRAM ASSESSMENT

In 1995 and 1997, the GAO evaluated aspects of the MQSA program. These favorable reports found that the initial impact of the new Federal law had been positive,

while the report that looked at mammography inspections found that facility compliance was continuing to improve.

FDA performed facility satisfaction surveys under both the interim and the final

regulations to review how facilities perceive the inspection process and the program’s educational and guidance materials. Based on these results, it is clear that

the vast majority of facilities see the MQSA inspection program as beneficial, particularly the educational approach of the inspectors that helps facilities identify

areas for improvement.

FDA continues to fine-tune the MQSA program to better serve the mammography

community, leading to higher quality care for the women of America.

REAUTHORIZATION

MQSA was reauthorized in October 1998, with the enactment of the Mammography Quality Standards Reauthorization Act (MQSRA). MQSRA mandated that patients be directly notified of their mammogram results, in lay language. The regulations were amended to reflect this mandate. Facilities quickly complied, and currently, there are almost no inspection violations in this area. In addition, a study

published in the February 2002 American Journal of Roentgenology surveyed patients before and after this requirement went into effect. The study found that there

was a substantial increase in the number of patients who reported timely receipt

of mammography results, and a substantial decrease in patients dissatisfied with

their results, all without an appreciable increase in patient anxiety.

Congress also requested FDA to determine if best-performing mammography facilities can maintain their high standards without the scrutiny of annual inspections. With input from the conference of Radiation Control Program Directors, FDA

designed a demonstration program whereby citation-free facilities from States who

agreed to participate were randomly assigned to study and control groups. Those

study group participants would begin skipping their next annual inspection, beginning in May 2002. After data collection is completed in the summer of 2004, data

analysis will be performed and a report will be presented to Congress in mid-2005.

Reauthorization of the appropriations authority for the Certification of Mammography Facilities would allow the Federal government to continue to ensure that all

mammography facilities provide high quality mammograms as an aid in the early

detection of breast cancer.

CONCLUSION

FDA has successfully implemented the MQSA program and has improved the

overall quality of mammography by constructing and implementing an effective program that holds all providers of mammography to the same standard. The MQSA

program in an invaluable tool in promoting public health and merits reauthorization.

ONCOLOGY NURSING SOCIETY,

PITTSBURG, PA 15220–2749,

February 26, 2002.

Hon. EDWARD M. KENNEDY,

U.S. Senate,

Washington, D.C. 20510.

Hon. JUDD GREGG,

U.S. Senate,

Washington, D.C. 20510.

DEAR CHAIRMAN KENNEDY AND RANKING MEMBER GREGG: On behalf of the more

than 29,000 nurses and other health professionals of the Oncology Nursing Society

(ONS), we are writing to inform you of our position on mammography screening for

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breast cancer and our concern about the impact of the recent report published in

the British medical journal, The Lancet, which concluded that no scientific support

exists for breast cancer screening with mammography. For your reference, we have

attached the ONS position paper on mammography, a public awareness ad supported by ONS on this issue, and a letter to the editor of the New York Times

signed by ONS and numerous other cancer related organizations voicing concern regarding the impact that The Lancet article could have on public health.

ONS, the largest professional oncology group in the United States, exists to promote excellence in oncology nursing, teaching, research, administration; education

in the field of oncology, and the provision of quality care to individuals affected by

cancer. As part of our mission, we stand ready to work with policymakers at the

local, state, and Federal levels to advance policies that will reduce and prevent suffering from cancer, including access to cancer detection tools that locate cancer early

when both the chances of survival and treatment outcomes are highest.

Breast cancer is the leading cancer and the second leading cause of death from

cancer in women in the United States. Additionally, for women between the ages

of 15 and 54, breast cancer is the leading cause of cancer-related death. Early detection of cancer, including routine mammography screening, has been shown to decrease a woman’s chance of dying from breast cancer. It is the position of ONS that:

• every woman has the right to make an informed decision about her need for

mammography screening;

• baseline mammography must occur for all women by age 40;

• screening mammography must be provided every year for all women ages 40

and older who are at average risk for the development of breast cancer;

• women at higher than average risk due to genetic or lifestyle factors must have

access to expert medical guidance to define the appropriate age to begin and the

frequency of mammography screening; and

• mammography must be included as part of routine follow-up care to detect the

recurrence in women who have been treated for breast cancer.

Although research continues to develop improved methods for early detection, at

the present time, high-quality mammography coupled with adequate clinical breast

exams remain the most effective means of early detection. ONS, like many in the

cancer community, are concerned about the impact that The Lancet journal article

will have on women’s decision to be screened for breast cancer, that lives may be

lost if women ultimately are dissuaded from having regular mammograms. Although the existing studies of mammography screening do have known limitations

and even some flaws in design, ONS does not believe that any compelling evidence

exists at this time that would warrant dropping the recommendation of mammography as a screening tool for the early detection of breast cancer.

ONS maintains that public and private health insurance plans, must continue to

provide coverage of—and access to—age and risk appropriate mammograpy screening for all women who seek it. ONS will continue to monitor the research and await

review by experts of these studies, as well as additional research in this area. To

that end, we are hopeful that much of the doubt recently cast upon mammography

will dissipate in light of last week’s U.S. Preventive Services Task Force (USPSTF)

recommendation calling for screening mammography, with or without clinical breast

examination, every one to two years for women ages 40 and over. In addition, last

week both the National Cancer Institute (NCI) and the U.S. Department of Health

and Human Services (HHS) reaffirmed their support of mammography; these statements further validate the value of this important cancer screening tool.

ONS stands by its position that every woman has the right to make an informed

decision about her need for mammography screening for the early detection of

breast cancer. Should you have any questions or need more information regarding

ONS’ position on this important public health matter, please do not hesitate to contact us at (412/921–7373) or our Washington Health Policy Associate, Ilisa Halpern

(202/857–8968).

Sincerely,

PAULA TRAHAN RIEGER, RN, MSN, AOCN, CS, FAAN,

President.

PEARL MOORE, RN, MN, FAAN,

Chief Executive Officer.

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PREPARED STATEMENT OF SAMUEL B. WALLACE

MAMMOGRAMS DETECT CANCER SUGGESTED NEW SYSTEMIC & LOCAL ANTIBIOTIC THER- APY THAT IS EFFECTIVE AGAINST MICRO BREAST CANCER CELLS, THUS THERAPY WAS

DEVELOPED BY SAMUEL B. WALLACE, AUTHOR OF THIS RESEARCH PAPER

Subject: Whether Mammograms save Breast Cancer Patient’s lives? Distinguishing Cancer Detection and Cancer Therapy with emphasis on more precise Systemic

and Local Therapy as I suggested in Subcommittee Hearings in 1979 in written testimony before Select Subcommittee on Cancer Research titled: ‘‘Frontiers in Cancer

Research.’’ Subcommittee on Health, House and Senate Committees Chaired by Senator Weicker and Chairman Natcher, May 1985 published in 1985 and 1986. Which

were confirmed by the Five Year Clinical Trials of Dr. Bonadonna, an NIH Grantee

as he reported in the Journal: CANCER RESEARCH, May 1988. The main point

of the debate on this issue suggests to me that perhaps there should be two categories of Doctors—a Doctor of Medicine and an Doctor of Surgery. One would deal

with the application of curative medicines and the other would deal with Surgical

Procedures which also culminate in the saving of human lives. Thus far all in the

field of Breast Cancer with the exception of Doctor Bonadonna place the emphasis

on drastic or minimal surgery with the area of Cancer Metastasis all but forgotten

or ignored. Thus the real issue seems to be justifying surgery rather than that of

treating and cuing Micro Cancer.

MAMMOGRAMS ONLY DETECT CANCER—IT IS NOT CLAIMED THEY CURE IT

Proponents on both sides of the raging Debate all agree on one point and that

is that Mammograms do detect Cancer better than any other medical device known

to Medical Science. However, because the use of mammograms with concurrent

Breast Cancer therapy of Surgery, radiation and chemotherapy does not produce a

positive long lasting cure, the critics of the results of Cancer therapy suggest that

perhaps mammograms should not be used because some forms of Cancer Therapy

are not very effective. Thus, in Breast Cancer therapy for small Breast Cancer Tumors ‘‘the size of pencil points there is concern that Surgery followed by Radiation

has produced only a very small increase in survival. While the benefits of early detection are unquestioned for larger sized tumors. It should be noted that the manufacturers of the Mammogram do not claim that their machine has any therapeutic

value but only that it is capable of detecting even small cancer cells at close to the

time of the breast cancer cells inception. Therefore the real issue is not about the

Mammograms that successfully detect even the smallest cancer cells in a very early

stage but the therapy that sometimes fails in curing the Breast Cancer.

The American Cancer Society in its 2nd Edition of Oncology 1996, Ch.12: Breast

Cancer indicated at P. 296:

‘‘Routine mammography (combined with good Breast Cancer Therapy) will reduce

Breast Cancer Morality by at least 30%. No strategy has been shown to have a

larger impact on breast Cancer Mortality and use of such techniques has not been

as well established for any other disease:Day, N.E.: ‘‘Screening for Breast Cancer.

British Medical Bulletin, 1991; 47: 400–415.’’

Time Magazine, February 18, 2002 in its article: Rethinking Breast Cancer P 50:

‘‘Doctors know what to do when they find tumors the size of marbles—. . . surgery,

radiation and chemotheopy. But what to do when the cancers are as (small) as

pencil points? Do you treat them as massive tumors or do you leave them alone?

30 years ago these small tumors called ‘‘DCIS’’ were diagnosed in 6% of time. . . .

Today it is approximately 20% largely because of detection . . .’’

The questions asked by the writers of the February article on ‘‘Rethinking Breast

Cancer’’ (Therapy) ‘‘do you treat small breast cancer tumors as you would massive

tumors or do you leave them alone?’’ is not a difficult one to answer since it is obvious from their article that medicine has met with some success in treating large

breast cancers, but not small ones. The obvious answer to that question is to find

a new way to cure small breast tumors.

Small breast cancer tumors the size of pencil points generally begin in either the

bone marrow and travel to the breast or begin in the small capillaries of the breasts

that lead to the breast ducts. This poses a special problem for the breast Cancer

Therapist. In the ordinary initial immune responses, the tissue macrophage and the

smaller neutrophils in breast tissue called ‘‘histiocytes of breast tissue increase and

immediately injest invading Bacteria and Viruses. Next, the neutrophils in the blood

increase as a result of a combination of chemical released by the infected tissue. In

acute infection, those Immune cells can act almost instantly. But in the case of precursor Cancer cells their action is much slower. There is a combination of chemical

substance released from the infected tissue including neutrophils which carry natuVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00100 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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1 N.Y. Times Feb. 12, 2002 D5 shows nonspecific therapy adds Antibiotics to all B.M. targeted

cells!

/Id. N.Y. Times Feb. 12, 2003 Sect. D5: Showing mechanism by which Immune and Blood

Cells are targeted to their destination by means of their receptors which attach to a matching

receptor at a specific location in the nearby blood vessel which is near a specific tissue type such

as the skin, GRR, GGH, or GTV protein cells, or the LVS, protein cells of the skeletal muscle

which has a similar target receptor, such as the rib cage bones to which the Breasts are attached which are also linked to the arteries and veins in the Bone Marrow. It is important to

note that many of these Immune Cells are Bone Marrow Macrophage which immediately ingest

the Antibiotic when an Antibiotic is Injected into the Bones. Thus, the macrophage become essentially Antibiotic Macrophage which carry quantities of Antibiotics to the Cancer Infected area

of the Breasts. See also: Nature Immunology 3, 189, Feb. 2002 ‘‘How GD94–NR G2A Receptors

regulate T4 Cell Immune Response by Moser . . .; NATURE MAGAZINE, Feb. 2002, ‘‘Reporting

that they have identified five area receptor codes which the matching Bone Marrow Blood vessels.

ral antibiotics, toxicins and immune hormones as well as therapeutic antibiotics

which are called ‘‘leucosytosis’’ inducing factor which diffuse from the precursor or

tumor cells into the blood where it is transported into the Bone Marrow. This action

also causes the circulating neutrophils carrying natural and man-made antibiotics

to move to the targeted cancer infected tissue.

However, in the case of the small capillaries 1 which lead to the breast cancer

ducts there are a number of barriers to the small capillaries which prevent the Antibiotics from being absorbed by the tissue and its capillaries which lead to the blood

system. In addition, the small tumors because of their size and density of their tissue can not absorb the Antibiotic when it is applied directly.

Therefore, in order to treat small sized tumors or their precursors they must be

treated by one of two routes by means of medication applied to the nose that enters

85% of the patient’s blood supply and is truly systemic in that it treats the patient’s entire blood system and entire glandular system. For most illnesses this is good

therapy which produces the immediate activation of complement the beginning of

the curative process which I indicated in Testimony Samuel B. Wallace, before Subcommittee of Health, House Ways and Means Committee Dec. 4th, 1975 was true

for a wide variety of Viral, Bacterial and Protozoa Illnesses.

When there are barriers to Antibiotic therapy, such as the Blood Brain Barrier,

as for example in the case of encephalitis of the brain, a slightly different approach

is necessary for the best results. And this is true not only for Breast Cancer but

also for of all things Lung Cancer where ordinary large cell treatment has not

worked for small cell lung carcinoma. In both, the Bone and Bone Marrow are it

would seem a far better route of application of the Antibiotic such as Penicillin or

Tetracycline. And that is because in both instances the bone marrow which has access to virtually all the immune cells also has immediate access to the small carcinoma or precursors of Breast Cancer or Lung Cancer through the skeletal system

which directly links both the Breast Tissue and the Lung Tissue including the small

capillaries in each case! And this also has to do with the particular ‘‘Defensins’’ or

natural antibiotic which are specific in neutrophils targeted for specific areas and

tissues of the body as explained in a splendid article in the American Society of

Microbiology News 5:56,315–320, 1990, the authors Robert Lehrer, Tomas Ganz and

Michael Selsted, Professors of Medicine, (UCLA) explain @ 315: ‘‘Researchers have

found a variety of Peptides (naturally occurring Antibiotics in man) with Antibacterial, antifungal, antiviral and cytotoxic Activities’’ called ‘‘Defensins’’ or natural

antibiotics.

‘‘Defensins’’ are ‘‘natural peptide antibiotics from neutrophils’’ or natural antibiotics produced by the human body to fight bacterial and viral infections including

cancer and leukemia’’ (asm) are a key to understanding: how the natural immune

response overcomes cancer.

In the recent past most Medical Textists while acknowledging that the Innate Immune System which they describe as: Antigen to Macrophage Activation and Macrophage to Complement Activation which in turn stimulates the activities of other

Macrophages such as Neutrophils in the Innate Immune Response and the activity

of NK Killer Cells and T Cells which kill Viruses in the acquired or Indirect response. But the Medical Textist do not explain the positive role of the chemotaxis

role of Antibiotics particularly in the Innate Immune Response by the direct application of Antibiotics to the Macrophage which leads to the instant activation of Blood

Serum Complement whose effects I discussed in my 1975 Testimony demonstrating

that the Alveolar Macrophage when Penicillin and an Immune Hormone were combined and applied as Nose Drops good therapeutic results were obtained that cut

in half the time it normally takes to produce a lasting cure. This therapy normally

used 10% of the Physician’s Desk reference recommended curative dosage for AntiVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00101 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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biotics. And I indicated that my 1975 Congressional testimony applied to: Viral,

Bacterial and Protozoa Illnesses.

While I indicated in my 1985 Testimony that such Alveolar Macrophage Antibiotic

Activation of complement could be important for the enhancement and protection of

the entire Immune system and in order to produce a more ‘‘Systemic’’ form of Cancer Therapy citing the important Research of Umtae Kim on Metastasis. And indeed, Tonagawa won the Nobel Prize by discussing T Cell Acquired Immunity without discussing the Macrophage and Innate Immunity and the chemotaxic role of the

Antibiotics in either form of Immunity.

The UCLA Professors of Medicine do discuss this important point in their article

in the American Society of Microbiology on the ‘‘DEFENSINS’’ or ‘‘NATURAL ANTIBIOTICS’’ produced by the human body in the activation of the Macrophage which

results in their activating complement, the beginning of the curative process in both

the specific and acquired Immune Response. They also mention on page 316 of the

same article that the same natural antibiotics have a I effect on tumors that have

targets cells in the skeletal system and target cells in Cancer infected tissue: (paraphrased)

Defensins are newly defined family of broad spectrum Antibiotics found in the leukocytes of humans and other mammals. . . . Human neutrophils contain four

principal Defensins. The four principal Defensins usually account for about 80%

of the Neutrophils total Defensin content. The Defensins contain 30 to 50% of the

total protein in human neutrophil’s . . . granule.’’

. . . Neutrophils are made by stem cells in the bone marrow.

‘‘Neutrophils are (also) Macrophages in the circulating blood. They are (highly flexible cells that enter infected tissues in large numbers (with) . . . the help of

chemotactic stimuli. (Such as the Antibiotics) It is estimated that the Neutrophil

Defensins account for as much as 7% of the protein content of the Neutrophils,

themselves which approximates the standard standard dosage of Antibiotics. The

Defensin delivery system by means of the neutrophil is more sophisticated than

any yet constructed by the pharmaceutical industry.

The Human Defensins HNP-I . . . exert nonspecific cytoxicity against various

human tumor cells that, depends on active target cell metabolism as found in the

skeletal systems or bones and in the tissue, glands, and blood vessels. For that reason and because the Neutrophil Defensins account for as much as 7% of the protein

content of the neutrophils themselves which is approximately the standard daily

dosage of (some) Antibiotics, the Neutrophils and other Macrophage produce an extraordinary impact on the Immune system, singularly where most viruses and Cancer, and Leukemia Precursors are normally thrown off. And therapeutically when

man made Antibiotic and Synthetic Immune Hormones are applied to the Immune

systems directly related to the specific and systemic Immune, blood, glandular and

skeletal immune systems.

Because as consequence of the neutrophils relation to humans immune system

and because of the enormous impact they can exert on all immune systems for

which they are targeted Neutrophils can be characterized as Macrophage that carry

Antibiotics (natural or man-made) as do all Macrophage to all the areas of infection

and inflammation caused by Virus, Bacteria and Protozoa including those caused by

Cancer, Leukemia and AIDS Infections which are more in that they are also Immune responses that have gone wrong which have produced severe genetic

mutations which effect the structure of the Immune and Metabolic systems in varying degrees.

Injection of Antibiotics into the surface of the cranium is a Bone Marrow Immune

System Therapy which is not only important to those suffering from brain damage

caused by ordinary diseases but also those caused by tumors. And it is safer and

more effective less invasive than any other form of therapy. Particularly, surgery

or radiation which one must recall are both very invasive Immune suppressing procedures. And in the recommended Antibiotic Therapy, the Macrophage and

Neutrophils play a key role searching for damaged or diseased brain tissue which

when found they instantly repair.

For example, I found in Brazil that encephalitis of the brain could be cured by

simply Injecting Tetracycline into the cranium. On the other hand, at John Hopkins

Hospital, the standard treatment for encephalitis of the Brain is removal of the diseased brain tissue which may result in paralysis and in some cases total disfunction

of the brain. Therefore, a simple procedure of Injecting an Antibiotic into the cranium is a safe and effective therapy for Encephalitis of the Brain which utilizes the

extraordinary properties of the Neutrophil Macrophage Immune Cell systems which

includes their ability to find diseased or damaged tissue and to apply both natural

and man made Antibiotics to that tissue when they are stimulated by the

99

chemotaxic effects of the added Antibiotics to the appropriate Immune System affected by Disease or Infection.

The ‘‘chemotaxic’’ effects on proteins including Immune blood cells causing their

movement particularly in conjunction with epinephrine and the production of the

ATP Enzyme and the release of C Amp the energy used to fuel cellular interactions

play a critical role in the Immune response and cause Immune cells such as the

Neutrophils or Macrophage to move toward the areas of Infection including areas

where tumors or even small micro tumor precursors reside. This process is best understood when the event is severe inflammation which is described by the Physiologist Guyton in ‘‘Human Physiology’’ 1982, P.48: ‘‘The tissue macrophage are the first line of defense against infection during its first

hour. Neutrophils move from the nearby Bone Marrow and the circulating blood

to the area of inflammation within a few hours after the onset of the infection

where they often increase four to five fold. Which is the result of a combination

of chemical substances that are released from the inflamed tissues called

leukosytosis inducing factor. This factor diffuses from the inflamed tissue into the

blood and is carried into the bone marrow . . . causing the release of many leukocytes, . . . especially large numbers of Neutrophils that are almost immediately

transferred from the bone marrow storage pool into the circulating blood or directly from the bone marrow by way of its blood vessels to nearby targeted tissue

which is inflamed.

When there is no inflammation the same basic process though considerably slower

is basically identical. And what is noteworthy is that not only antigen or disease

can initiate this macrophage-Neutrophil activation of complement, but that man

made Antibiotics applied to macrophage can do the same thing, particularly when

they are injected into the Bone of patients infected with cancer or leukemia.

While the standard procedure of removal of diseased brain tissue may cause the

patient to be completely paralyzed or in some cases no longer living. In addition the

costs of such surgical procedures are enormous—costing at least twenty thousand

dollars per operation while the extremely safe injection of the Antibiotic into the

surface of the cranium costs pennies per injection of Antibiotics and leaves the patient fully functional. Thus, such diseases of the brain can be treated by the manmade Antibiotics applied to the surface of the cranium where the neutrophils bearing Natural Antibiotics or ‘‘Defensins’’ also reside and are activated by the addition

of man made Antibiotics causing the sensitized Neutrophil Macrophage Cells to seek

the diseased brain tissue and to treat it effectively by causing the Activation of

Blood Serum Complement. And given the proclivity of the Neutrophils and other

Macrophage to seek damaged and inflamed tissue when stimulated, the addition of

Injected Antibiotic to the bone marrow of the cranium could lead to good treatments

for wide variety of Brain Damage caused Neurological diseases such as Multiple

Sclerosis, Parkinson’s Disease, Autism and Epilepsy. Direct Injection into the surface of the cranium is recommended.

This then is further indication that Injecting Antibiotics into the Bone Marrow,

also for Breast Cancer Patients and small cell Lung Cancer would be effective in

light of the role the natural Defensin Antibiotics play in the Bone Marrow Immune

system responses to diseases of the brain an excellent therapy which imitates the

natural Immune activity of the Natural Antibiotic Defensins in the Neutrophil

Macrophages own immune response. The anatomy of the Bone Marrow Rib cage

which are linked to the Breast tissue by means of common arteries and veins as

well as the linkage of the rib cage veins to the Breast Cancer Glands and Blood

Vessels also suggests that such treatment would be actually enhancing the normal

immune response of the Breasts to potential malignancies which are often defeated

by the normal immune response in that area.

The fact that this form of therapy has been tested in over 50 Clinical trials

against Cancer and Leukemia as reported on the Japanese Internet in 1999 as I

suggested in 1985 is also a strong indication that Injection of Antibiotics into the

Bone for Breast Cancer is a reasonable alternative to the Invasive and Mutilating

Procedures of Radiation and Surgery. The Antibiotic therapies are not only very effective but are also very inexpensive and invariably would yield good results in

treating micro sized Breast Cancer Cell and would prevent metastasis as does Dr.

Bonadonna’s Breast Cancer Clinical Trials show . . . Dr. Bonadonna does not suggest the mild inexpensive and effective Antibiotic Bone Marrow therapy, perhaps because of NIH Policy which favors the unsafe and largely ineffective Bone Marrow

Transplant Program which it sponsors. Thus there are two paths through which the

Bone Marrow enter the nearby Breast tissue: One route is the application of the

Antibiotic nose drops that treats the entire blood and glandular system which pass

through the Breasts. Another is by way of the Microphage-Antibiotic entry by Injection into the rib cage beneath the Breasts where arteries and veins go into the nearVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00103 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
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2 Arthur Guyton’s: HUMAN PHYSIOLOGY AND MECHANISM OF DISEASE, 3rd Edition

1982, p.56. . . .‘‘The complement System . . . is composed of 9 Enzymes which are normally

inactive but which can be activated by Antigen-Antibody reactions or (Macrophage to Complement reactions) . . . 4. Chemotaxis (of complement): ‘‘One or more of the complement products cause chemotaxis of the Neutrophils and Macrophages, thus enhancing the number of

macrophage and neutrophils in the area of the infection. 5. . . Complement often attacks structure of Viruses neutralizing them.

P.46: . . . Properties of Neutrophils, Macrophages and Monocytes: . . . The Neutrophils,

Macrophage and Monocytes that mainly destroy invading Viruses, Bacteria and other invading

infections. The Neutrophils can destroy Viruses even in the circulating Blood. Macrophage are

mature monocytes which also destroy viruses.

P.48: . . . Tissue Macrophage, . . . the Alveolar Macrophage of the Lungs, the microglia of

the Brain immediately go to work against infections and are the First Line of defense against

infections in the first hour which also respond to inflammation of tissue including the elevation

of temperature.’’ (The fact that a Nasal Decongestant containing epinephrine combined with the

Antibiotic Penicillin (called aptly by the Japanese: Penicillin Diversum) can activate Complement and reduce fevers that are caused by virus or bacteria with seconds of the Application

of the Nose Drops is of great medical significance as I indicated in Congressional Testimony Dec.

4, 1975.) Also in the initial Immune response many neutrophils go from the Bone into the Circulating Blood and from thence to the Infected Tissue carrying Defensin Antibiotics.

by Breast Tissue where they link with target areas in the Breast tissue. Both forms

of Breast Cancer therapy are examples of Innate Immune Therapy.

All three forms of Innate Macrophage Therapy also activate an Acquired Immune

response which embraces Acquired Immunity with the additional benefits of sensitized T Cells activity which along with the Macrophage and the NK Killer Cells

are capable of destroying the Breast Cancer Tumors and Leukemia Viruses. In addition, the sensitized T Cell Acquired Immunity provides long term Immunity against

Breast Cancer. It is also important to note that the Bone Marrow Immune system

like the Lungs is linked to the Glandular System as well as the Blood System. 2

Therefore combining the systemic therapy of Penicillin Nasal Decongestant Nose

Drops and Injection of Antibiotics into the rib cage proximate to the Breasts should

lead to a very high cure rate for most forms of Breast Cancer including particularly

the incipient DCIS which infect the Breast Ducts.

ECONOMIC IMPACT OF THIS INNATE ANTIBIOTIC THERAPY FOR BREAST CANCER

Those Professors of medicine are to be praised not for discussing a ‘‘new discovery’’ in medicine, but for their courage, candor and honesty in discussing a fact

known to science and the entire American and European Pharmaceutical Industry

since the early 1970’s when Dr. Hamao Umezawa, Md. And Professor of Medicine

Tokyo University indicated in the Japanese Journal of Antibiotics 1977: 30

(Supp.):138–63 in an extensive article titled: ‘‘Recent Advances in bioactive microbial

secondary metabolites’’ that he had discovered ‘‘secondary derivative antibiotics’’ made in the human body by a process of screening human blood. A simple process

used now by the American and European Pharmaceutical Companies in which

Human Blood, Animal and Fish Blood and even plants, animals, and earth are

screened by simple centrifugal force, which separates the samples according to their

molecular weights.

What makes this method for Discovery of new Antibiotics produced by man, animals, fish and plants important to mankind is that it is extremely simple and extremely inexpensive to do as compared to the elaborate and costly procedures for

discovery of Antibiotics by means of Enzyme or Protease Inhibitors a process used

by Dr. Hamao, Umezawa to discover hundreds of Antibiotics that cure Cancer and

Leukemia such as Bleomycin a beta lactam (penicillin) compound discussed by the

NIH’s Dr. Chabner as Editor of Oncology: Goodman’s and Gilman’s Pharmacology

1996 Edition. And why was the article by Professor Lehrer et al. of UCLA based

on a lecture he gave in Houston, Texas in 1989 so significant? Because the NIH to

this very day in the year 2002 still claims that the Antibiotics are incapable of Curing Viruses from the simple Asthma Virus to HIV I and III Leukemia! Despite

Goodman’s Pharmacology 2nd Ed. on page 1388 it authors indicating they do. Which

adds immensely to the cost of government and private health program’s. The NIH

in taking the unscientific policy position that the Antibiotics (natural or man-made)

are not Antiviral Agents despite the American Cancer Society and generally AMA

doctors success in curing virally caused Cancer using hundreds of Antibiotics also

contradicts a medical text that it authored in 1955: Goodman and Gilman’s. ‘‘The

Pharmacological Basis for Therapeutics’’, 2nd Edition which on page 1346–1347 indicated that the Antibiotic Penicillin combined with a Nasal Congestant Nose Drops

was a Cure for Asthma. Which I confirmed in Congressional Testimony before the

Subcommittee of Health of the House Ways and Means Committee, Dec. 4th, 1975

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entific policy is that today people who are infected with the Asthma rhino virus are

given Antiviral Asthma Agents that cost $5,000 to $10,000 per year until they finally succumb to Asthma virus infection. Which means in Government Programs

the Federal Treasury looses Billions of dollars annually and many patient’s die from

Asthma and other viral illnesses that can not be cured by means of the NIH’s Antiviral Agents which the NIH admits can not cure Viral Illnesses. The UCLA Professors medicine who in their 1990 article published in the ASM News had showed

great courage showing that the human body produces natural antibiotics which cure

viruses. A finding similar to my own as I had indicated based on my own empirical

tests in Brazil from 1969 to 1974 that man-made Antibiotics cure a wide range of

ordinary viral illnesses in a shorter period of time using ten percent of the PDR required curative dosage which I reported in my Congressional Testimony Dec. 4th,

1975. I informed members of Congress and former Secretary of HH&S Ms. Shalala

that the Antibiotics cure HIV I and III Leukemia in the 1980’s and 1990’s. I participated in two FDA Conferences of Physicians sponsored by David Kessler where I

discussed the same Issues. And at an informal gathering on Capitol Hill I briefly

discussed the Antibiotics effectiveness at an AIDS Conference in which Dr. Fauci

was one of the officials present on stage.

THE ECONOMIC IMPACT OF USING SAFE AND EFFECTIVE ANTIBIOTIC THERAPIES

The economic impact to this approach to medicine is very positive. For Puerto

Rico as was pointed out by a Ms. Pagan in Health Care and Financing Review/Summer 1983, Vol. 4, No.4: the Puerto Rican Public Health System is at least 95% more

efficient than the stateside American Public Health System, (which I have personally experienced while teaching in Puerto Rico) because the Public Health System

of Puerto Rico relies more heavily on Antibiotics.

This is similar to the experience of the Japanese, Canadians and Hawaiian Health

Systems all of whom rely more heavily on Antibiotic Therapy which produce far

more cures. Which leads me to believe that some thought should be given to directing medical studies to Medicines, only. Thus, a doctor could be a doctor of medicine

or a doctor of Surgery. The Medical doctor’s Education would emphasize the roll of

medicines and the human immune response through the studies of Pharmacy and

Immunology and Biochemistry. And would be for six years rather than twelve.

Thereby reducing the cost of Medical School by 50%. While surgery would emphasize gross anatomy and physiology, surgical procedures and why it is important to

treat surgical wounds immediately after surgery with antibiotics as well as always

finding new techniques for the delivery of Antibiotics for the delivery of Antibiotics

to various areas of the human body even when those techniques sometimes required

minor surgery. This division of Medicine into two separate categories: ‘‘Doctor of

Medicine and Doctor Of Surgery’’ would be more appropriate—so that more medicine oriented procedures could be developed through Biochemistry, Pharmacology,

Immunology and Physiology for Doctors of Medicine. Which would lower the costs

of both who would be required to study the essentials of the Medical Science and

Pharmacy. At the same time those training to be Surgeons would also have their

curriculum shortened because they would not have to be quite so knowledgeable

about Medicine. Both disciplines would place emphasis on finding the cure of illnesses rather than on long esoteric studies attempting always to find the cause of

disease. And those studying Medical Science only would have fully interrelated

Science courses that related their individual science courses to Medicine as a whole.

BEST INNATE ‘‘SYSTEMIC’’ CURATIVE THERAPY: ANTIBIOTIC DECONGESTANT NOSE DROPS

Ordinarily Injection of Antibiotics into the veins is considered sound ‘‘Systemic’’

Therapy. However, that form of Therapy treats the Immune System through

Veinular Blood System neglecting the glandular system. It is significant, that Penicillin and Tetracycline Nasal Decongestant Nose Drops That I Rediscovered in

Brazil in 1969 or 1970 whose effectiveness against Bacteria, Viruses etc. I reported

in Testimony before the Subcommittee on Health of the House Ways and Means

Committee Dec. 4, 1975 is probably the best Curative Therapy for HIV I and III

because I proved that a very wide range of illnesses were cured in a far shorter period of time with ten percent of the PDR’s recommended Curative Dosage as well

as Goodman and Gilman’s: The Pharmacological Basis of Therapeutics 1955–1958

Edition, P. 1346–47: ‘‘A Cure for Asthma: Penicillin and a Nasal Decongestant’’ as

well as the Spanish Pharmacopoeia 1993 edition: ‘‘Nasal Decongestant Cures Respiratory Illnesses’’ indicates that such Therapy is the most effective ‘‘systemic’’ therapy for a wide range of Viral and Bacterial Illnesses. And should always be used

in ‘‘Systemic’’ Therapy for all forms of Cancer and Leukemia. That application of

Antibiotic Nose Drops is the best form of ‘‘Systemic’’ Therapy is also shown because:

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(1) Application of the Antibiotic Nose Drops treats the entire Glandular system to

which the Lungs are attached as well as the entire Blood system through which

Blood passes through the Lungs through the heart. That form of treatment is

truly ‘‘Systemic’’ in that it enters into all the systems of the Immune System.

(2) This is also proven by empirical evidence because as is indicated in the Spanish

Pharmacopoeia 1993: ‘‘A Nasal Decongestant Nose Drops combined with Penicillin

Cures Respiratory Infections.’’

(3) My Empirical tests in Brazil indicate that it cures a wide range of Bacterial and

Viral Illnesses. And that it reduces severe bacterial and viral fevers soon after it

is applied as Nose Drops. This same form of therapy generally uses only ten percent of the normal initial curative dosage as recommended by the PDR which is

500 mg Penicillin for the treatment of Pneumonia, for example. The Nose Drops

produce the same effect with only 50 mg of Penicillin, which begins the curative

process immediately activating Blood Serum Complement, which is proved by its

ability to reduce fevers as soon as it is applied as nose drops.

(4) Adriamycin has been designated by the American Cancer Society as the most

effective Anti-cancer and Leukemia Agent, the Japanese Pharmaceutical Industry

proved in Chemical Abstracts April 15, 1985 that PD-3; Penicillin Diversum combining synthetic epinephrine—Naphazoline Hcl in weak solution with Penicillin

was 98% effective against Bone Cancer in vitro, the highest rating ever given an

Anticancer Antibiotic in vitro.

(5) Other forms of Cancer such as Breast Cancer have been cured with the common

Antibiotics such as Penicillin, Adriamycin and Bleomycin (a Penicillin complex

compound)

(6) The Antibiotic Nasal Decongestant Nose Drops also act as an Amazing

Immunological growth factor that can cause the Immature Stem Cells that proliferate in Leukemia Patients to begin growing once more which reverses the Leukemia proliferation process.

No other form of Systemic Therapy uses smaller quantities of Antibiotic to

produce Cures in much shorter periods of time. See Testimony Samuel B. Wallace,

Subcommittee of Health of the House Ways and Means Committee, Dec. 4th, 1975.

Therefore, it is the best ‘‘Systemic’’ therapy for Breast Cancer, Bone Cancer and

Leukemia is the application of the Antibiotic Nasal Decongestant Nose Drops which

treats the Lung Immune System, the most powerful Immune System in the human

body because it is directly linked to both the Blood and Glandular Systems. This

is confirmed by a prestigious Cancer Research Institute in Japan as well as by NIH

Grantee Dr. Bonadonna’s five year Clinical Studies for Breast Cancer,2 which has

produced Cure Rates as high as 80% for Breast Cancer.

INJECTION OF ANTIBIOTICS INTO THE BONES IS THE BEST ‘‘LOCAL’’ (LOCAL—SYSTEMIC)

ANTIBIOTIC THERAPY

...

In 1985, this author proposed an alternative to treating the Bone Marrow with

medicines that were both safe and effective—namely, by Injecting Antibiotics into

the Bone in my Testimony given before the Subcommittees on Health of the House

and Senate Appropriations Committee May 1985. In that Testimony indicated that

all forms of Cancer should be treated ‘‘Systemically’’ and ‘‘Locally’’ with the Curative

Antibiotics and that the Antibiotics should be Injected into the bones of Cancer Patients in order to thoroughly treat such Patients and in order to prevent future reoccurrence and metastasis, citing the ten year work of Dr. Umtae Kim of the Rosewell

Institute, Buffalo, N.Y. Injection of Antibiotics into the bone is the safest way to Administer Antibiotics and can even be given to new-borns before their veins are fully

matured. My own research indicates that Injection of Antibiotics into the Bones,

thus treating the bone Marrow Immune System is second only to the Nasal Decongestant Nose Drops in effectiveness. Thus, such treatment reduces a fever within

approximately an hours time, while the Antibiotic Nasal Decongestant Nose Drops

reduces the fever shortly after it is applied. Clinical Studies by Japanese Oncologists

have proven that Injection of Antibiotics into the Bone is a very powerful and effective form of Cancer and Leukemia Therapy because there were in 1999 50 Clinical

Trials where Injection of Antibiotics were given in the Treatment of Cancer and

Leukemia. Therefore it would seem logical that this safe and effective Cancer and

Leukemia Therapy would also prove effective against HIV III AIDS Leukemia which

resides in the Bone Marrow as well of course in the Lymph Nodes, Blood and

Glands. Therefore, the Best Form of Antibiotic ‘‘Local’’ Curative therapy for HIV III

Patients is Injection into the four limbs and the surface of the cranium, as well as

injection into the AIDS Patient’s Lymph Nodes because:

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(1) It is in the Bone Marrow that Immune Cells normally grow and where obviously

HIV Leukemia suppresses the growth of normal immune cells including the B, T

and Macrophages and particularly the T4 Immune Cells which play an important

role in the Regulation of the Immune Cells in the Immediate Immune Response

as well as influencing the role of the circulatory Lymphocytes. (Susumi Tonegawa

the Noble Laureate emphasized that without the T Cells even in the case B Cell

and macrophage complement activity that those responses without the T Cell participation would fail. (See Scientific American, October 1985, Tonegawa on the

Molecular activity of the Immune Cells, Page 128. Therefore Injection of Antibiotics into the Bone treats the HIV AIDS Infection in its locus.

(2) The Bone Marrow Immune System is the second only to the Lung Immune System in its power to begin the Immune Response and then effecting a Positive result, which is a Cure. For example, applying a Nasal Decongestant Antibiotic as

Nose Drops to the Lung Immune System initiates the Curative Process immediately as is shown by its ability to reduce Bacterial and Viral Fevers which is

accomplished almost immediately. Reduction of Fevers by Injection into the Bones

is accomplished within one or two hours far shorter times than is normal which

generally takes four to six hours. See the Medical Physiologist, Arthur Guyton.

(3) Injection of Antibiotics into the Bone thus Treating the Bone Marrow Immune

System has proven to be one of the most effective ways to Treat and Cure various

forms of Cancer and Leukemia. See Japanese Internet 1999 showing 50 Clinical

Trials where Antibiotics cured various forms of Cancer and Leukemia.

In May 1988, Dr. Bonadonna, a Surgeon at Instituto Tumari, Milan, Italy and

also an NIH Grantee indicated in Cancer Research May 1988 Treating Breast Cancer ‘‘Systemically’’ and ‘‘Locally’’, produced over a five year period higher Cure Rates

than with Surgery or Radiation. That modality of Breast Cancer Antibiotic Therapy

has produced Cure Rates as high as 80% but has not been applied to other forms

of Cancer and Leukemia by the NIH.2

THE EXISTENCE OF DEFENSINS IN THE HUMAN BODY MANUFACTURED BY MYELOID

PRECURSOR CELLS IN THE BONE MARROW IS SIGNIFICANT FOR SEVERAL REASONS

The existence of Natural Human Antibiotics which are produced by myeloid precursor cells residing in the bone marrow and stored in the cytoplasm granules of

mature cells that are capable of destroying bacteria and viruses is significant for

several reasons:

First it destroys a fundamental fallacy where the NIH contradicted its own Text

Goodman & Gilman’s Pharmacology 2nd Ed. 1955–1958, Pharmaceutical Conferences in 1940 to 1950 and Armed Forces Records WWII and the American Cancer

Society’s and Japanese Doctors success in treating and curing Cancer and Leukemia

Viruses with the Antibiotics. This contradictory conduct by the NIH is the basis for

its reliance on ineffective and unsafe Antiviral Agents which have displaced low cost

Safe and Effective Antibiotic Medicines that have long cured HIV I and sometimes

HIV III Leukemia. This NIH fallacy has resulted in the World-wide AIDS Epidemic

which has been characterized as Security Issue by the United Nations and may

have resulted in the infection of more than 100 Million human beings.

Second, the displacement of the low cost safe and effective Antibiotic Medicines

by the NIH’s Unsafe and ineffective nostrums has resulted in the rise in the cost

of Medicines from 5,000 fold to 20,000 fold and has produced many new categories

of formally curable illnesses being reclassified as incurable. i.e. Asthma.

Third, the failure to make available synthetic Antibiotic Medicines has resulted

in unnecessary loss of human life. And now animal life with the wholesale destruction of livestock caused by fear of infected animals who are now not given precautionary Antibiotics.

THE DISCOVERY OF TUMORICIDAL ALVEOLAR (LUNG) MACROPHAGE & NEUTROPHILS

WHICH CARRY ‘‘DEFENSINS’’ OR NATURAL ANTIBIOTICS INDICATE IMMUNE CELLS COMBINED WITH ANTIBIOTICS CAN CURE CANCER, LEUKEMIA AND HIV I AND III

This author during the years 1970–1974 by his use of Innate Antibiotic Therapy

(activation of Macrophage Direct activation of Complement) in Brazil discovered and

described the effects of Antibiotic carrying Macrophage and Neutrophils activity in

the Innate Immune Response. Which I describe in the Testimony of Samuel B. Wallace, Subcommittee of Health of the House Ways and Means Committee Dec. 4th,

1975, the effects of Antibiotic Macrophage and Neutrophil carrying Natural Antibiotics (Defensins). ‘‘The Antibiotic Nasal Decongestant Nose Drops’’ can:

1. Reduce Fevers to Normal Level: Viral, Bacterial and Protozoa Fevers instantaneously. Since, only the Macrophage can act instantaneously and the curative

process begins with the activation of complement), the reduction of fever is an inVerDate 11-MAY-2000 10:49 Nov 21, 2002 Jkt 000000 PO 00000 Frm 00107 Fmt 6633 Sfmt 6621 S:\DOCS\78085.TXT SLABOR3 PsN: SLABOR3
104

3See GAN TO KAGAKU RYOHO 2000 July; 27(8): p. 1191–2000: ‘‘Tumor microcirculation and

selective enhancement of drug delivery-clinical applications.’’ Dept. of Internal Medicine, Sendai

Shakaihoken Hospital . . . using Yoshida Sarcoma (Bone Marrow Cancer Tumors) functional

differences in microcirculation between tumor (tissues) and normal tissues were found by Suzuki

et al. in (1977’’ ...’’ It is very important after chemotherapy to understand . . . the

pathohistological changes in tumor(s) and (their) . . . repaired tissues, which present various

clinical images.’’ (Whether those ‘‘Clinical Images’’ have an effect on Mammographic Images is

an open question that I would assume depends to some extent upon the degree of Tumor tissue

density.) . . . In conclusion: ‘‘IHC (continuous infusion of Angiotensin II ‘increased tumor blood

flow’) might be applied to all kinds of tumors to (including of course small cell Breast Tumors)

to enhance the chemotherapeutic effects through selective increase of drug delivery to tumors.’’

This study at Sendai Hospital Japan was devoted to Cancer Tumor in general, and did not

refer specifically to small Cell Breast Cancer or small Cell Lung Cancer. But it did note that

there was a great difference in normal tissue and tissue that was infected with Cancer Tumors.

And that differences in tissue made a difference in the effectiveness of the delivery of drugs to

the area of tumor infection. It does therefore at least support my theory which was proven with

respect to encephalitis of the brain that there are barriers to the delivery of medicines to tissue,

such as the well known ‘‘Blood-Brain Barrier’’ and I believe the small capillaries of the Breast

as well as the circulatory barriers to the Lungs. Which helps to explain why doctors have not

met with success in treating Small Cell Breast Cancer or Small Cell Lung Cancer. The following

three Papers borrowed from my own work on another Leukemia topic, I suggest from my own

empirical studies in Brazil from 1969 prove the importance of the routes of Antibiotic Delivery

in treating Cancer Tumors as well as the more common infections and neurological diseases titled:

BEST INNATE SYSTEMIC CURATIVE THERAPY ANTIBIOTIC DECONGESTANT NOSE

DROPS

INJECTION ANTIBIOTICS INTO BONES BEST LOCAL (&SYSTEMIC) ANTIBIOTIC

THERAPY

THE EXISTENCE OF DEFENSINS IN BODY MADE BY . . . PRECURSOR CELLS IN

BONE MARROW IS SIGNIFICANT FOR SEVERAL REASONS

This author, Samuel B. Wallace has enclosed those three pages based on his Research in

Brazil 1969 to 1974 because he believes they may be helpful in developing new methods for the

delivery of Antibiotic Medicines in Breast Cancer and Cancer and Leukemia Therapy. All three

pages have been tested by Samuel B. Wallace, in Brazil.

dication that the curative process has begun which is a sure indication that serum

complement has been activated instantaneously.

2. Can cure most Viral and Bacterial Illnesses in three days time. The more difficult

illnesses can be cured in a third less time.

3. Curative dosage required to begin the curative process by activation of Complement is ten percent of the dosage recommended by THE PHYSICIANS DESK

REFERENCE. For example PDR, recommends 500 mg Penicillin for Pneumonia,

but using the Antibiotic Nose Drops the amount of medication required is ten percent of PDR recommendation or less than 5 mg per nose drop dosage.

4. Can cure most Virus, Bacteria or Protozoa Illness is a strong indication of a major

break through in Medical Science. The discovery or rediscovery of an almost resistance free Curative therapeutic.

The four effects of the Innate Antibiotic Therapy: Immediate reduction of Viral,

Bacterial and Protozoa, Fevers, the ability to cure most Viral, Bacterial and Protozoa Illnesses in three days, smaller curative dosages of Antibiotics which have the

same effect as larger recommended dosages, and a medicine that can cure most illnesses is a very strong indication of better utilization of the patient’s immune system and better placement of the medication in that immune system in achieving

cures in a shorter period of time. And since only the Macrophage the predominant

Immune System can act so swiftly to get natural and made Antibiotic to the locus

of the Infection and beginning the curative process through the activation of complement. All of this is strong indication of a Direct Response of the Innate Immune

system which is Macrophage to Direct activation of complement. Which begins the

Curative Process.

On the other hand, the experiments of Kazuyoshi Imaizumi, N. Hasegawa et al.

who found that stimulation of the Aleveolar Macrophage and Antigen Presenting

Cells through the CD40 and CD40L complement receptors which expressed tumor

cells could enhance the cytotoxic effect of macrophages and the Antitumor Immunity

of the T Cells by using alfa Interferon Leukosyte fragments to stimulate Macrophage Antitumor activity against Lung Cancer cells were inconclusive and ambiguous.3 Example: (Tested Macrophage prestimulated with Penicillin!)

The effectiveness of the Innate Macrophage Immune Therapy: Macrophage to direct activation of complement and its immediate therapeutic effects is better tested

against actual disease than against some remotely connected Antigen such as an

Antibody or leucocyte particle. Which demonstrates far more effectively the ability of

the Macrophage or other Immune Cells to act against Virus or Bacteria. And a better

105

understanding of the effectiveness of an Antibiotic Therapy is better determined by

the length of time that red blood serum complement is activated by the Macrophage

which in turn has been activated by an Antibiotic or an Antibiotic combined with

an Immune Hormone.

A more effective laboratory test of the Macrophage’s ability can be determined by

the number of new Antibiotics found in the Macrophage both natural (Defensins)

and man-made after the Macrophage have activated Blood Serum complement.

Therefore, even though showing ‘‘stimulating the Alveolar Macrophage through its

CD40 and CD40L Complement Receptors’’ is of great significance, it is of even more

significance to demonstrate that an Immune Cell actually reacts to a specific disease

by producing new natural antibiotics or Defensins to fight the disease. Or that it

acts in general against a wide range of diseases of one type or another. Kazuyoshi

et al. did use tumor cells in their experiment, but not Antibiotics in sufficient

strength to strongly exhibit a tumoricidal effect! No curative dose! They, did not

show Antibiotic to Macrophage: direct and instant activation of complement shown

by the immediate reduction of fevers, and the cure of an extremely wide variety of

bacterial, viral and protozoa illnesses in 1970 to 1974 for which many U.S. Pharmaceutical companies are today allegedly seeking to find a cure. And which led the

Japanese Pharmaceutical Industry to dub this author’s rediscovery ‘‘. . . Penicilium

Diversum’’ Chem. Abstr,. April 15, 1985 and as being 98% effective against the

deadly sarcoma ‘‘yoshida sarcoma’’ or bone marrow Cancer, is of more value to Medical science than the dubious discovery that an esoteric cellular immunity or acquired

immunity fragment from a T cell Leukocyte Fragment also called ‘‘alfa interferon’’

has some impact on the macrophage because it means that ‘‘researchers’’ had failed

to take into account the Macrophage’s ability to do its most important work, its ability to Directly Activate red blood serum complement as well as its ability to reduce

Viral Fevers and to achieve cure rates better than 90%, even though they nibbled

around the edges of this discovery by proving that the Macrophage have

Antitumoricidal properties by testing the Macrophages’ Complement Receptors.

A better more Scientific approach would have been to test the complement receptors against some disease or virus said to be incurable such as Asthma or HIV AIDS

using their approach or mine which consists of the Antibiotic stimulating the Alveolar Macrophages’ Complement Receptors by showing that that approach actually activates red blood cell complement, thus beginning the Curative Process. The use of

very weak or dubious indicators such as Interferon or Interleukin II–12 is of very

little significance because those indicators, themselves, only produce cure rates of

5% or slightly better, while Antibiotics such as Penicillin or tetracycline alone or

combined with synthetic Immune Hormones such as synthetic epernephrine produce

cure rates against the same viruses. And the question remains that an experiment

that uses a stronger stimulant the Antibiotics to ‘‘preserve’’ the Macrophage in culture, whether such ‘‘preservation’’ may have prestimulated the Macrophage before

the test of the Macrophage’s by means of weak CD-40 receptors and weak Interferon

and Interleuken 2. Thus, invalidating the entire experiment.

[Whereupon, at 5:10 p.m., the joint hearing was concluded.]

Æ