In support of early small studies,[65,66] a retrospective study of 551 women with disease-associated BRCA1 or BRCA2 mutations found a significant reduction in risk of breast cancer (HR 0.47; 95% CI, 0.29-0.77) and ovarian cancer (HR 0.04, 95% CI, 0.01-0.16) after RRSO. A prospective single-institution study of 170 women with BRCA1 or BRCA2 mutations showed a similar trend. With RRSO, the HR was 0.15 (95% CI, 0.02-1.31) for ovarian, fallopian tube, or primary peritoneal cancer, and 0.32 (95% CI, 0.08-1.2) for breast cancer; the HR for either cancer was 0.25 (95% CI, 0.08-0.74). A prospective multicenter study of 1,079 women followed for a median of 30 to 35 months found that, while RRSO was associated with reductions in breast cancer risk for both BRCA1 and BRCA2 mutation carriers, the risk reduction was more pronounced in BRCA2 carriers (HR = 0.28; 95% CI, 0.08-0.92). A meta-analysis of all reports of RRSO and breast and ovarian/fallopian tube cancer in BRCA1/BRCA2 mutation carriers confirmed that RRSO was associated with a significant reduction in breast cancer risk (overall HR = 0.49, 95% CI, 0.37-0.65; BRCA1 HR = 0.47, 95% CI, 0.35-0.64; BRCA2 HR = 0.47, 95% CI, 0.26-0.84).
In addition to the reduction in incidence of both breast and ovarian cancer, a prospective multicenter cohort study of 2,482 BRCA1/BRCA2 mutation carriers has reported an association of RRSO with a reduction in all-cause mortality (HR = 0.40, 95% CI, 0.26-0.61), breast cancer-specific mortality (HR = 0.44, 95% CI, 0.26-0.76), and ovarian cancer-specific mortality (HR = 0.21, 95% CI, 0.06-0.80).
Level of evidence: 3ai
Tamoxifen (a synthetic antiestrogen) increases breast-cell growth inhibitory factors and concomitantly reduces breast-cell growth stimulatory factors. The National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (NSABP-P-1), a prospective, randomized, double-blind trial, compared tamoxifen (20 mg/day) with placebo for 5 years. Tamoxifen was shown to reduce the risk of invasive breast cancer by 49%. The protective effect was largely confined to estrogen receptor-positive breast cancer, which was reduced by 69%. The incidence of estrogen receptor-negative cancer was not significantly reduced. Similar reductions were noted in the risk of preinvasive breast cancer. Reductions in breast cancer risk were noted both among women with a family history of breast cancer and in those without a family history. An increased incidence of endometrial cancers and thrombotic events occurred among women older than 50 years. Interim data from two European tamoxifen prevention trials did not show a reduction in breast cancer risk with tamoxifen after a median follow-up of 48 months  or 70 months, respectively. In one trial, however, reduction in breast cancer risk was seen among a subgroup who also used hormone replacement therapy (HRT). These trials varied considerably in study design and populations. (Refer to the PDQ summary on Breast Cancer Prevention for more information.)