Background: To prospectively assess the efficacy of bilateral risk-reducing mastectomy (BRRM) when compared with surveillance on breast cancer (BC) risk and mortality in healthy BRCA1 and BRCA2 mutation carriers.Patients and methods: Five hundred and seventy healthy female mutation carriers (405 BRCA1, 165 BRCA2) were selected from the institutional Family Cancer Clinic database. Eventually, 156 BRCA1 and 56 BRCA2 mutation carriers underwent BRRM. The effect of BRRM versus surveillance was estimated using Cox models.Results: During 2037 person-years of observation (PYO), 57 BC cases occurred in the surveillance group versus zero cases during 1379 PYO in the BRRM group (incidence rates, 28 and 0 per 1000 PYO, respectively). In the surveillance group, four women died of BC, while one woman in the BRRM group presented with metastatic BC 3.5 years after BRRM (no primary BC), and died afterward, yielding a HR of 0.29 (95% CI 0.02-2.61) for BC-specific mortality. Conclusions:In healthy BRCA1/2 mutation carriers, BRRM when compared with surveillance reduces BC risk substantially, while longer follow-up is warranted to confirm survival benefits.

A majority of women would choose the procedure again, but adverse effects and untoward changes in the perception of the sexual relationship need to be addressed in the counselling of women at high risk, to optimize an informed choice and enable adequate adjustment postoperatively.

BACKGROUND:We assessed the efficacy of taxane chemotherapy in BRCA1-and BRCA2-associated patients compared with sporadic metastatic breast cancer patients. METHODS: Response rates (RRs) to and progression-free survival (PFS) after taxane chemotherapy of 35 BRCA1-associated and 13 BRCA2-associated metastatic breast cancer patients were compared with those outcomes in 95 matched (1:2) sporadic patients. Matching was performed for age at and year of diagnosis of primary breast cancer, year of metastatic disease, and line of therapy (first vs second or third). RESULTS: Among BRCA1-associated patients, the RR was worse (objective response [OR], 23% vs 38%; progressive disease [PD], 60% vs 19%; P < 0.001); and the median PFS shorter (2.2 vs 4.9 months; P ¼ 0.04) compared with sporadic patients. In the subgroup of hormone receptor (HRec)-negative patients, BRCA1-associated patients (n ¼ 20) had a worse RR (OR, 20% vs 42%, respectively; PD, 70% vs 26%, respectively; P ¼ 0.03) and a shorter PFS (1.8 vs 3.8 months; P ¼ 0.004) compared with sporadic patients (n ¼ 19). These outcomes in HRec-positive patients were similar in BRCA1-associated (n ¼ 11) and sporadic (n ¼ 61) patients (OR, 36% vs 38%; PD, 28% vs 20%; median PFS, both 5.7 months). In BRCA2-associated patients, who were mainly HRec-positive, the OR was higher than in sporadic patients (89% vs 38%, respectively; P ¼ 0.02), whereas the median PFS was not significantly different (7.1 vs 5.7 months, respectively). CONCLUSIONS: BRCA1-associated, HRec-negative metastatic breast cancer patients were less sensitive to taxane chemotherapy than sporadic HRec-negative patients. HRec-positive BRCA1-and BRCA2-associated patients had a sensitivity to taxane chemotherapy similar to that of sporadic patients. Cancer 2012;118:899-