Breast Cancer Chemoprevention for BRCA1 and BRCA2 Carriers
William J. Gradishar, MD
Tamoxifen reduced risk for contralateral breast cancer in patients with either mutation.
Women who carry BRCA1 or BRCA2 mutations have a significantly elevated lifetime risk for developing breast cancer and ovarian cancer. The risk is reduced by >90% with bilateral mastectomy and by 50% with premenopausal bilateral salpingo-oophorectomy. Data demonstrating the benefit of nonsurgical risk-reduction strategies have been less compelling. Large prevention trials with tamoxifen have clearly demonstrated that risk can be reduced by 40% to 50% in at-risk women, though not necessarily in mutation carriers, yet uptake of tamoxifen for prevention has been disappointing. One prospective trial in the primary-prevention setting (JAMA 2001; 286:2251) suggested that tamoxifen reduced the risk in BRCA2 carriers (hazard ratio, 0.38) and increased risk in BRCA1 carriers (HR, 1.67), but it was a substudy, and the confidence intervals were wide.
Now, to evaluate the effect of tamoxifen on the risk for contralateral breast cancer in mutation carriers who have already developed cancer in one breast, investigators pooled observational cohort data on 2464 eligible patients from three independent academic organizations. Among patients with known estrogen-receptor (ER) status, the first breast cancer was ER negative for 76% of BRCA1 mutation carriers and ER positive for 77% of BRCA2 mutation carriers. Tamoxifen was taken after first breast cancer diagnosis by 383 (24%) of the 1583 BRCA1 carriers and 454 (52%) of the 881 BRCA2 carriers.
A total of 520 contralateral breast cancers were diagnosed during 20,104 person-years of observation. The adjusted hazard ratios for contralateral breast cancer risk associated with tamoxifen use were 0.38 and 0.33 for BRCA1 and BRCA2 carriers, respectively. Analysis of only the prospective data showed a similar impact of tamoxifen (HR, 0.58 for BRCA1 carriers; HR, 0.48 for BRCA2 carriers) during 4392 person-years of prospective follow-up.
Citation(s):
Phillips K-A et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2013 Aug 5
