Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers

Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high r isk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in o varian hormone exposure following bilateral prophylactic oophorectomy (i.e. , surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylac tic oophorectomy is associated with a reduction in breast cancer risk in BR CA1 mutation carriers. Methods: We studied a cohort of women with disease-a ssociated germline BRCA1 mutations who were assembled from five North Ameri can centers. Surgery subjects (n 43) included women with BRCA1 mutations wh o underwent bilateral prophylactic oophorectomy but had no history of breas t or ovarian cancer and had not had a prophylactic mastectomy. Control subj ects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and gear of birth. Res ults: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (H R) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08- 0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. U se of hormone replacement therapy did not negate the reduction in breast ca ncer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy i s associated with a reduced breast cancer risk in women who carry a BRCA1 m utation. The likely mechanism is reduction of ovarian hormone exposure. The se findings have implications for the management of breast cancer risk in w omen who carry BRCA1 mutations.