Breast-cancer genes 1 and 2 (BRCA 1, BRCA2) encode for proteins involved in tumor suppression. The BRCA1 gene, located on chromosome 17, is involved in cell-cycle checkpoints in response to DNA damage and DNA repair. The BRCA2 gene, located on chromosome 13, is involved in the repair of double-strand DNA breaks
Women with BRCA1\2 mutations have a significantly increased risk of developing ovarian and breast cancer. BRCA1 mutation carriers have a 44% risk of ovarian cancer (OC) and 72% risk of breast cancer (BC) BRCA2 mutation carriers have a 17% risk of OC and 69% risk of BC. Other types of genetic mutations also increase the risk (see table).
International guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) after completion of childbearing or at 35–40 years of age for BRCA1 mutations carriers or at 40–55 years of age for BRCA2 (ref here). The current National Comprehensive Cancer Network guidelines recommend that bilateral salpingo-oophorectomy also be considered for carriers of BRIP1, RAD51C, and RAD51D at ages 45–50 years and that hysterectomy along with bilateral salpingooophorectomy be considered for those with Lynch syndrome
Hormonal replacement 6(HRT) among RRSO patients does not appear to significantly alter postsurgical breast cancer risk Moreover, a possible protective effect of HRT on BC in BRCA mutation carriers has been reported, with a reduction of 8% of cancer risk for every year of an estrogens-only regimen and an increase of 8% of cancer risk for every year of progestin-only regimen. A subgroup analysis carried out in Italy including women before the age of 45 undergoing RRSO observed a 18% reduction in BC risk for every year of estrogen-only replacement and a non-significant increase in BC risk of 14% for every year of a combined therapy (study here).
Tamoxifen (and raloxifene) appears to reduce the risk of breast cancer by 62% in BRCA2 mutation carriers but has not been found to reduce the risk of breast cancer among BRCA1 mutation carriers. This likely reflects the lower prevalence (10–24%) of estrogen receptor-positive breast cancer among BRCA1 mutation carriers; whereas BRCA2 mutation carriers have tumors that are predominantly (65–79%) estrogen receptor positive.