# Presentation: 654948

## Breast Cancer Screening

**Eve Espey, M.D.**
**University of New Mexico **

## Objectives

**To explain the epidemiology of breast cancer among US women**
**To understand screening modalities and current breast cancer screening recommendations **
**To discuss strategies to reduce risk of developing breast cancer**

## 2003:  211,300 new cases of breast cancer and 39,800 deaths
32% of all newly diagnosed cancers in women are cancers of the breast
Most common cancer diagnosed in women
Most feared health condition by women

**32% of all newly diagnosed cancers in women are cancers of the breast**
**Most common cancer diagnosed in women**
**Most feared health condition by women**

**Epidemiology of Breast Cancer**

**Notes:**
Incidence has increased over the past decade due to:
       1)  Mammographic screening - detecting more pre-invasive or 
	in-situ cancers as well as earlier invasive cancers
      2) Aging of the population

## Leading Sites of Cancer Incidence and Death in Women (1997 Estimates)

**	****	****	****   ****CANCER****	****             CANCER**
**RANK****	****	**** INCIDENCE****	****	****   DEATHS**
**   ****1****	****	****     Breast****	****	****      Lung**
**	****	****	****    ****192,200****	****	****     66,000**
**   ****2****	****	****      Lung****	****	****     Breast**
**	****	****	****      ****79,800****	****	****     40,200**
**   ****3****	****	****Colon/Rectum****	****Colon/Rectum**
**	****	****	****      ****64,800****	****	****     27,900**
**   ****4****	****	**** Corpus Uteri****	****     Ovary**
**	****	****	****     ****34,900****	****	****     14,200**

## Selected Cancer Statistics by Ethnicity

## New Mexico Breast Cancer Data

**Notes:**
The incidence in Native American women is around 1/3 that of Caucasians but in those who develop breast cancer, the survival is less than that in white women who get the disease.  I.e., as a Native American, your risk of breast cancer is much lower, but if you get it, you’re more likely to die from it.  Probably NOT based on biological differences in types of cancer but rather:
	- Geographic access issues in treatment
	- Cultural differences
	- Until recently, less screening mammography

It has been thought that Native American women are more likely to be young when they develop breast ca.  The impression comes from the fact that the age structure of Navajo population is very different from the general pop, with a much larger proportion of young women.  If rates are age-adjusted, no difference in incidence rates, with age remaining a very strong risk factor.

## Cancer Mortality Rate Ratio for Females, 1994-98, AI/AN Compared to U.S. All Races

***AI/AN rate statistically different from US All Races death rates **

**.5**

**.75**

**1**

**1.5**

**2**

**All Sites**
**Lung**
**Colon/Rect.**
**Ill Def/Unk.**
**Breast**
**Stomach**
**Liver**
**Pancreas**
**Kidney**
**Ovary**
**Esophagus**
**Cervix**
**Gallbladder**

## Slide 8

## Risk Factors for Breast Cancer

**Female gender**
**Age over 50**

**Notes:**
Note:  The most important risks are inescapable, gender and age.  Women in general, however, overestimate their risk of breast cancer and fail to understand the importance of age as a risk factor.

## Age

**Notes:**
- Age 40s:  127 / 100,000
Age 50s:  348 / 100,000
Age 60s:  450 / 100,000

Breast ca rare in 20s, but increases steeply with age after 30 with a peak incidence in the 80s.

## Putting Breast Cancer Risk in Perspective

**The “1 in 9” statistic**
**Cohort of 1000 women**
**By age 85:**
**33 dead from breast cancer**
**99 will have diagnosis of breast ca**
**203 dead from CV disease****	****	**

**Notes:**
Excellent article which takes a critical look at the commonly quoted 1 in 9 statistic:  I.e., 1 in 9 chance of developing breast cancer.  Article shows that the actual risk of breast cancer is complex (as it refers to cumulative risk over time) and difficult to explain to patients.  There are studies which show that women tend to overestimate their own risk of breast cancer and fail to understand the importance of age as a risk factor.   It then explains the risk in a variety of ways, one of which is the life table.  Data from the Ontario Cancer registry suggests that with a birth cohort of 1000 women:
	By age 40, 17 will be dead but not of breast cancer
	In the 40s and 50s, 9 will die of breast cancer, 9 of CV dz
	In the 60s and 70s, 18 will die of breast cancer, 105 from
		CV disease
	By 85, total of 33 dead from breast cancer, although a total
		of 99 will have the disease
	          total of 203 dead from CV disease

## Putting Breast Cancer Risk in Perspective

**1 woman in 9 develops breast cancer**
**That woman has a 50% chance of being diagnosed after age 65**
**That woman has a 60% chance of surviving breast cancer and dying of another cause**

## Fear of Breast Cancer

**Survey of 1000 women age 45-64**
**Condition they feared most:**
**Breast cancer:  61%**
**Cardiovascular disease:  9%**

## Other Major Risk Factors

**Family History**
**1st degree relative**
**Premenopausal**
**Bilateral cancer**
**Personal History**
**Breast cancer**
**Carcinoma in situ**
**Atypical hyperplasia**

**Notes:**
If you did risk based screening, only pick up 20-25% of breast cancers.  Therefore, screening programs need to target the main risk factors:  female gender and age.  I.e., all women over certain age cutpoints are screened.

current age 
age at menarche 
number of breast biopsies 
age at first live birth 
number of first-degree relatives with breast cancer 

## Minor Risk Factors

**Late age at first pregnancy**
**Nulliparity**
**High socioeconomic status**
**Exposure to high dose radiation**
**Hyperplasia on breast biopsy**

## Risk factors for BRCA 1 and BRCA 2

**Breast and ovarian cancer**
**2 or more relatives < 50 with breast cancer**
**Male breast cancer**
**> or = 1 relative < 50 with breast cancer + Ashkenazi Jew**
**Ovarian cancer + Ashkenazi Jew**

**Notes:**
100 specific genetic mutations – tumor suppressor genes
Lifetime risk of breast cancer 60-80%
BRCA 1 – also cervical, endometrial pancreatic ca
RX:  Intensified screening
Prophylactic mastectomy
Oophorectomy – decreases ovarian > 90% and breast > 50%
Tamoxifen

## Breast cancer and HRT	

**5 years of ERT does not increase risk**
**5 years of HRT increases risk by 26%**

## Unproven Risk Factors

**Oral contraceptives**
**Obesity**
**High fat diet**

## Breast Cancer Screening

**Breast self exam (BSE)**
**Clinical breast exam (CBE)**
**Mammography**

**Notes:**
A good screening test is one which allows intervention to substantially reduce morbidity and mortality of the disease.  These three tests have been proposed.  

Some mathetmatical evidence based on doubling times that mammography COULD identify a non-palpable mass of 1 mm to 1 cm in the 3 years before it became palpable at about 2 cm.  

\Mammography is by far the most studied of the three and appears to have the most promise of reducing M&M.
SBE:  We have traditionally encouraged women to do BSE every month 
CBE:  Traditionally performed once a year

Sensitivity:  Likelihood of testing positive if disease is present
Specificity:  Likelihood of testing negative if the disease is absent
PPV:  If test is positive, disease truly present
NPV:  If test is negative, disease not present

## USPSTF and Canadian TFPHCRating of evaluations

**A:  *****Strong***** recommendation to include the service **
**B:  *****Recommendation***** to include the service **
**C:  *****No***** recommendation either for or against**
**D:   *****Recommendation against***** routine provision of the service **
**I:   Evidence insufficient **

**Notes:**
A:  Good evidence that the service improves health outcomes
B:  At least fair evidence that the service improves health outcomes
C:  At least fair evidence that the service can improve outcomes but balance of benefits and harms too close to call
D:  At least fair evidence that the service is ineffective or harms outweigh benefits
I:  Insufficient evidence

## Breast self exam:Canadian Task force on Prevention

**Fair evidence of no benefit **
**Good evidence of harm **
**Overall fair evidence that routine teaching of BSE should be excluded from the annual exam**
**D recommendation**

- June, 2001

## USPSTF:  2002 Should we recommend BSE?

**BSE:  insufficient evidence to**
**recommend for or against**
**“****I” recommendation**

## Studies evaluating BSE

**2 RCTs, 1 quasi RCT, 3 case-control studies**
**No difference in breast cancer mortality**
**No difference in stage of cancer at diagnosis**
**More provider visits:  8% vs. 4%**
**More benign biopsies**

**Notes:**
Chinese 266,000 women age 39-72 in monthly BSE with extensive training, 2 reinforcement sessions, multiple reminders:  Planned for 10 year F/U – powered to find 30% difference in mortality.  At 10 years, no difference in mortality (135 vs. 131)

Russia:  122,000 women aged 40-64 with similar BSE teaching.  No difference in mortality at 9 years.

Neither has reached maturity but a large benefit would be unlikely and the continuation of both studies is threatened from a political perspective.
Chinese and Russian study:  no benefit
Non-randomized trial of BSE in UK
Nested case control in a Canadian screening study 
NO REDUCTION IN MORTALITY

## ACOG Practice Bulletin:  Breast cancer screening       April, 2003

**Despite a lack of definitive data for or against breast self-examination, breast self-examination has the potential to detect palpable breast cancer and can be recommended.**

## Costs of BSE

**$700 per competent frequent self-examiner**
**Opportunity cost:  limited time for counseling**
**Anxiety, worry, depression**

## Should we recommend mammography?

|  | 1996 | 2002 |
| --- | --- | --- |
| Ages 40-49 | C | B |
| Ages 50-65 | A | B |
| Age > 70 | C | B |
|  |  |  |

## Disadvantages of Screening Age 40-49

**1/3 of women undergoing annual**
**screening mammography between**
**40-49 will have an abnormal mammo**
**requiring:**
**Further imaging studies**
**FNA or core biopsy**
**Excisional biopsy**

## Does mammography work?	

**2001:  Cochrane review by Olsen and Gotzsche found no reduction in mortality**
**5 of 8 trials seriously flawed**
**3 “sound” trials showed no benefit**
**Methodological flaws negate findings of benefit **

**Notes:**
All of the 8 trials were done before the current stringent and exacting format for a population-based randomized trial was established AND no consensus about the ideal design for a population based RCT to assess mammography.

## Does mammography work?	

**2002:  USPSTF reviewed Cochrane findings**
**Only 1 trial seriously flawed**
**Flaws “problematic” but unlikely to negate findings of benefit**
**Downgraded recommendation (A to B) but included all women **_**> **_**40**

**Notes:**
Problems with data:  1980’s inferior technique, single view vs standard 2 views, longer screening intervals...

## Mortality is declining

**1990-1999:  breast cancer mortality has decreased by 17%**

## New screening technologies	

**Full-field digital mammography**
**Computer-assisted detection**
**MRI**
**Ultrasound**

**Notes:**
FFDM:  Digital images have enhanced resolution over mammography
Ultrasound:  Increased detection at the expense of a lot of false positives
MRI: Better detection but studies have included only small numbers of cancers
CAD:  May enhance sensitivity of mammography—should be studied in large prospective trials – like a spellchecker, helping radiologists detect lesions

## Screening Mammogram ReportsBirads

**Birads 0:  Incomplete study**
**Birads 1:  Normal, routine follow-up**
**Birads 2:  Benign finding, routine follow-up**
**Birads 3:  Probably benign finding, 6 month ****	****	****	****	****follow-up**
**Birads 4:  Suspicious finding, consider biopsy**
**Birads 5:  Highly suspicious, biopsy required**

**Notes:**
Normal:  unequivocally benign - follow up for age
Probably benign:  1-2 % risk - follow up 6 months
Probably enign: 3-20% risk - stereotactic biopsy
Possibly malig > 20% risk of cancer - surgical biopsy

## Limitations of Mammography

**Palpable masses must be evaluated despite  NEGATIVE results**

## Slide 34

**Notes:**
44 y/o woman with palpable breast lump.  Ultrasound showed a cystic lesion and mammogram was negative.  Physician told her that unlless the mass grew larger or became painful, she would not need any treatment.  He suggested that she eliminate caffeine.  20 months later, she presented with nipple discharge and was diagnosed with breast cancer.  She won $625,000.

## Slide 35

## Gail Model

**http://bcra.nci.nih.gov/brc/**
**Calculates 5 year risk of developing breast cancer**
**Age**
**Age at menarche**
**# of breast biopsies**
**Age at first live birth**
**Number of first degree relatives with breast cancer**

## Reducing the risk of breast cancer

**Chemoprevention**
**Tamoxifen and raloxifene:**
**38% decrease in breast cancer incidence?? Reduction in mortality**
**Tamoxifen**
**Endometrial cancer, DVT**
**Raloxifene**
**DVT**

**Notes:**
13,000 women randomized to tamoxifen vs placebo
Premenopausal women with risk of 1.67% chance of developing breast ca in 5 years derived benefit

## Chemoprevention

**NSAIDs??**
**2 or more tabs/wk of ASA/ibuprofen led to a 21% decrease in breast cancer risk in the WHI trial**

## Reducing the risk of breast cancer

**Prophylactic surgery**
**Bilateral mastectomy**
**Reduces risk by 90%**
**Bilateral oophorectomy**
**Lifestyle**
**Reduction in fat intake, exercise, weight loss, reduction in alcohol**

##    Summary

**Take down your shower card for BSE**
**Encourage mammography**
**Work up palpable masses**
**Don’t worry quite so much...**