Life expectancy gains from cancer prevention strategies for women with breast cancer and BRCA1 or BRCA2 mutations.
BACKGROUND
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.


METHODS
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.


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


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


METHODS
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.
Schrag
D
D
Department of Adult Oncology, Center for Outcomes and Policy Research, Dana-Farber Cancer Institute, Boston, Mass, USA.
Kuntz
K M
KM
Garber
J E
JE
Weeks
J C
JC
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control*; D003661:Decision Support Techniques; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008017:Life Expectancy; D008390:Markov Chains; D008408:Mastectomy; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control*; D010052:Ovariectomy; D011379:Prognosis; D012306:Risk; D013629:Tamoxifen / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors; D013629:Tamoxifen