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Deborah Schrag, MD, MPH; Karen M. Kuntz, ScD; Judy E. Garber, MD, MPH; Jane C. Weeks, MD, MSc

JAMA. 2000;283:617-624.

Context  Women with BRCA1- or BRCA2-associated breast cancer are at increased risk for contralateral breast cancer and ovarian cancer and therefore may consider secondary cancer prevention strategies, such as prophylactic surgery and tamoxifen therapy. It is not proven to what extent these strategies reduce risk of second cancers in such patients.

Objective  To examine the effect of tamoxifen therapy, bilateral prophylactic oophorectomy (PO), prophylactic contralateral mastectomy (PCM), and combinations of these strategies on life expectancy for women with unilateral breast cancer and a BRCA1 or BRCA2 gene mutation.

Design and Setting  Decision analysis using a Markov model. Probabilities for developing contralateral breast cancer and ovarian cancer, dying from these cancers, dying from primary breast cancer, and the reduction in cancer incidence and mortality due to prophylactic surgeries and/or tamoxifen were estimated from published studies.

Participants  Hypothetical breast cancer patients with BRCA1 or BRCA2 mutations facing decisions about secondary cancer prevention strategies.

Interventions  Seven strategies, including 5 years of tamoxifen use, PO, PCM, and combinations of these strategies, compared with careful surveillance.

Main Outcome Measures  Total and incremental life expectancy (LE) with each intervention strategy.

Results  Depending on the assumed penetrance of the BRCA mutation, compared with surveillance alone, 30-year-old early-stage breast cancer patients with BRCA mutations gain in LE 0.4 to 1.3 years from tamoxifen therapy, 0.2 to 1.8 years from PO, and 0.6 to 2.1 years from PCM. The magnitude of these gains is least for women with low-penetrance mutations (assumed contralateral breast cancer risk of 24% and ovarian cancer risk of 6%) and greatest for those with high-penetrance mutations (assumed contralateral breast cancer risk of 65% and ovarian cancer risk of 40%.) Older age and poorer prognosis from primary breast cancer further attenuate these gains.

Conclusions  Interventions to prevent second cancers, particularly PCM, may offer substantial LE gain for young women with BRCA-associated early-stage breast cancer. Estimates of LE gain may help women and their physicians consider the uncertainties, risks, and advantages of these interventions and lead to more informed choices about cancer prevention strategies.

Author Affiliations: Department of Adult Oncology (Drs Schrag, Garber, and Weeks) and the Center for Outcomes and Policy Research (Drs Schrag and Weeks), Dana-Farber Cancer Institute, and the Department of Health Policy and Management, Harvard School of Public Health (Dr Kuntz), Boston, Mass. Dr Schrag is now with the Health Outcomes Research Group, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.

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Benefit of Prophylactic Mastectomy for Women With BRCA1 or BRCA2 Mutations
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