Breast Cancer Incidence After Risk-Reducing Salpingo-Oophorectomy in BRCA1 and BRCA2 Mutation Carriers

Abstract

Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers effectively reduces ovarian cancer risk, but also reduces breast cancer risk. Breast cancer risk reductions up to 50% have been reported for both BRCA1 and BRCA2 mutation carriers, but recent prospective studies were not able to reproduce this finding for BRCA1 mutation carriers.Breast cancer incidence after RRSO was assessed in a consecutive series of 104 BRCA1 and 58 BRCA2 mutation carriers. On the basis of data from our own centre, and assuming a 50% risk reduction through RRSO at premenopausal age, we expected to find 8 breast cancers (range 6-10) in this population for the reported screening period (532 women-years).In 162 carriers with a median age of 41 years at RRSO, 13 incident breast cancers were diagnosed. In BRCA1 mutation carriers, 12 incident breast cancers were found compared with 5 (range 3-6) expected and in BRCA2 mutation carriers 1 breast cancer was found compared with 3 (range 2-5) expected.Breast cancer incidence after premenopausal RRSO is still high, especially in BRCA1 mutation carriers. Previously reported breast cancer risk reductions up to 50% were not confirmed. As a consequence, continued intensive screening for breast cancer is warranted in BRCA1 and BRCA2 mutation carriers after RRSO. Cancer Prev Res; 5(11); 1291-7. Ó2012 AACR.

Management of women at high risk of breast cancer

“…Nevertheless, ongoing breast surveillance is still recommended in these women and there are some prospective case series that suggest the incidence of breast cancer after risk reducing bilateral salpingo-oophorectomy is still high. 33 The ideal age for risk reducing bilateral salpingo-oophorectomy remains uncertain, but studies suggesting an earlier age of onset of cancers in carriers of the BRCA1 mutation support earlier intervention compared with carriers of the BRCA2 mutation. A surgical menopause can result in acute symptoms and long term risks of oestrogen deficiency.…”

Variation in Mutation Spectrum Partly Explains Regional Differences in the Breast Cancer Risk of Female BRCA Mutation Carriers in the Netherlands

“…This may have led to a higher percentage of censored cases in the study population. Therefore, the breast cancer risk could be underestimated in the study population as compared with the carrier reference population, because after these censoring events some carriers will develop breast cancer (31). Because the medical files were available, underestimation of the risk due to missing data on breast cancer, ovarian cancer, or preventive surgery is unlikely.…”

Which screening strategy should be offered to women with BRCA1 or BRCA2 mutations? A simulation of comparative cost-effectiveness

“…An inherent limitation of simulation modelling is that some of the included parameters are associated with uncertainty—in our model, these uncertainties are predominantly determined by the uncertainties in the lifetime risk of developing breast cancer, and also in the preclinical growth model parameter, as indicated by the sensitivity analysis of the main model output. As there is a lot of international variability in the uptake of prevention strategies in BRCA1 and BRCA2 mutation carriers, and as their effect is under debate, this was not included in our model (Metcalfe et al , 2007; Fakkert et al , 2012). …”