# Presentation: 669547

## Cancer Intervention and Surveillance Modeling Network:  Scientific UpdateBreast Cancer Initiative  National Cancer Advisory BoardJune 14, 2006

**Donald Berry PhD.**
**M.D. Anderson Cancer Center**
**Houston, TX**

## Joint Analysis: Breast Cancer Base Case

**Assess Impact of Adjuvant Therapy & Screening Mammography on US Breast Cancer Mortality, 1975-2000**

## Population Models

## Mammography Screening Over Time, Women ages 40-79

## Dissemination of Adjuvant TherapyAges 50-69, node-positive, stages II/IIIA

**Both**

**Polychem**

**Tamoxifen**

**None**

**Dissemination of Adjuvant Therapy****Ages 50-69, node-positive, stages II/IIIA**

## Modeling Results

## One Group’s Mortality Rate per 100,000 Women 40-79 under Various Scenarios

**One Group’s Mortality Rate per 100,000 ****Women 40-79 under Various Scenarios**

## Percent reductions in BC mortality due to adjuvant Rx and screening

**Percent reductions in BC mortality ****due to adjuvant Rx and screening**

## Percent reductions in BC mortality due to adjuvant Rx and screening

**Percent reductions in BC mortality ****due to adjuvant Rx and screening**

## Conclusions

**Screening lowers BC mortality**
**Population treatment benefit similar to clinical trials**
**Little evidence for synergy**
**Some model differences**
**Overall robustness across models**

## New York Times Editorial

**  ****“****What seems most important is that each team found at least some benefit from mammograms. The likelihood that they are beneficial seems a lot more solid today than it did four years ago, although the size of the benefit remains in dispute”**

**New York Times Editorial**

## Principal Publications

***JNCI***** Monograph, summer 2006**
**Common inputs**
**Model descriptions**
**Comparisons of **
**Modeling assumptions**
**Intermediate outcomes**
**Mortality outcomes**

**Principal Publications**

## The Future

## The Future

**Individual groups modeling risk factors, optimal screening schedules, high-risk populations, disparities**
**Some groups participating in HP2010**
**Base case II: Modeling impact of new (mostly individualized) treatments on breast cancer mortality rates**

**The Future**

## The Future

**New targeted treatments:**
**Trastuzumab (Herceptin)**
**Lapatinib (Tykerb)**
**Bevacizumab (Avastin)**
**Aromatase inhibitors**
**Individualized therapy:**
**Adjuvant!Online**
**OncoType Dx**
**Chemotherapy benefit by ER/HER2**
**Chemoprevention:**
**Tamoxifen**
**Raloxifene****	**

## Relapse-free and Overall Survival Benefit of Trastuzumab (Herceptin) in HER2+ Adjuvant Breast Cancer: B31/N9831

## Cumulative Effects: Higher Dose Doxorubicin + Paclitaxel + Dose-Dense by ER Status

**Berry et al. JAMA 2006**

**Cumulative Effects: Higher Dose Doxorubicin + Paclitaxel + Dose-Dense by ER Status**

## Benefits of Paclitaxel on Disease-Free Survival by HER2 and ER Status

**Notes:**
These curves represent DFS of the combined sets 1 and 2 by ER and by HER2, as assayed by immunohistochemistry with MAb cb11.
Shown on your left, patients who were ER negative benefited from paclitaxel, 
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but the benefit appears smaller in HER2 negative patients, in the top panel, than in HER2 positive patients, shown in the bottom panel.
ER positive patients are illustrated in the right panels.  While HER2 positive patients, shown in the lower right bottom panel, again appeared to benefit from paclitaxel, 
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In this analysis there was no apparent benefit from paclitaxel for those women whose cancers were ER Positive and HER-2 negative.
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This subgroup, ER Positive HER-2 Negative patients, represents more than 1⁄2 of the subjects in this study.
Evaluation of paclitaxel benefit according to ER and HER-2 was highly exploratory, and not powered for appropriate statistical analyses for a 3 way interaction.

## CISNET Breast Cancer Investigators

**Dana Farber Cancer Institute: Marvin Zelen, ****Sandra J. Lee, Hui Huang, ****Rebecca Gelman **
**Erasmus University: Dik Habbema, ****Sita Y.G.L. Tan, Gerrit J. van Oortmarssen, Harry J. de Koning, Rob Boer**** **
**Georgetown University: Jeanne Mandelblatt, ****Clyde B. Schechter, ****K. Robin Yabroff, William Lawrence, Bin Yi, Jennifer Cullen **
**MD Anderson Cancer Center: Donald Berry, Lurdes Inoue, Mark Munsell, John Venier, Yu Shen, Greg Ball, Emma Hoy, Richard Theriault, Melissa Bondy **
**Stanford University: Sylvia Plevritis, Bronislava Signal, Peter Salzman, Peter Glynn, Jarrett Rosenberg, Sanatan Rai **
**University of Rochester: Andrei Yakovlev, ****Alexander V. Zorin, ****Leonid G. Hanin **
**University of Wisconsin: Dennis Fryback, Marjorie A. Rosenberg, Amy Trentham-Dietz, Patrick Remington, ****Natasha K. Stout, Vipat Kuruchittham**** **
**National Cancer Institute: Eric J. Feuer, Kathleen A. Cronin, Angela Mariotto **
**Cornerstone Systems Northwest: Lauren Clarke**