Risk-reduction strategies. There is weak evidence to support the use of tamoxifen or other synthetic estrogen reuptake modulators (SERMs) to reduce breast cancer risk in women with BRCA mutations. Many of these cancers do not express estrogen receptors, which may explain the lack of efficacy in certain cases. Several observational studies have shown that tamoxifen can reduce the risk of contralateral breast cancer in women with BRCA mutations who have already been diagnosed with cancer in the other breast.29-31 However, tamoxifen does not reduce a patient’s risk of ovarian cancer, and it may increase her risk of uterine cancer.
Prophylactic bilateral mastectomy is the mainstay of breast cancer prevention in this population. Data from a systematic review suggest that this surgery may prevent the incidence of breast cancer in women with BRCA mutations by 90% to 95%.32 However, this review did not demonstrate a reduction in mortality from breast cancer, likely due to poor data quality.32 The National Comprehensive Cancer Network (NCCN) recommends discussing prophylactic mastectomy with all women who have BRCA mutations.28 Further conversations are important to review the risk of tissue left behind and quality-of-life issues, including the inability to breastfeed if the woman wants more children and the cosmetic changes with reconstruction.
Ovarian cancer screening and risk-reduction strategies
Screening. No effective screening strategy has been endorsed for ovarian cancer, as most previous studies have shown screening to be ineffective.26,33 Recently, studies both in the United Kingdom and the United States have investigated a screening strategy using the risk-of-ovarian-cancer algorithm (ROCA), which calculates an individual’s risk based on serum levels of cancer antigen 125 (CA-125).34,35 These studies measured CA-125 levels every 3 to 4 months followed by transvaginal ultrasound if CA-125 increased substantially (as determined by ROCA). Absent an abnormal increase in CA-125, transvaginal ultrasound was performed annually. These screening strategies showed improved specificity over annual screening programs, and the cancers detected were more likely to be diagnosed at an early stage (stage II vs stage III) and had higher rates of zero residual disease after surgery compared with those detected 1 year after screening ended.34,35 However, survival data are not yet available. More research is needed to determine if more frequent screening approaches could improve survival in high-risk women.
NCCN and the American College of Obstetricians and Gynecologists (ACOG) do not endorse routine screening with transvaginal ultrasound and serum CA-125 for high-risk women, as the benefits are uncertain. However, they do advise that these screens may be considered as a short-term strategy for women ages 30 to 35 who defer risk-reducing surgery.26,36 The USPSTF does not make a recommendation regarding ovarian cancer screening in high-risk women.37
Risk-reduction strategies. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only recommended technique for reducing the risk of ovarian cancer in women at high risk.26,33,36 Meta-analyses have shown an 80% reduction in ovarian cancer risk16 and 68% reduction in all-cause mortality with this approach.38 The NCCN recommends RRSO for women with a known BRCA1 mutation between the ages of 35 and 40 who have completed childbearing.36 Since the onset of ovarian cancer tends to be later in women with BRCA2 mutations, it is reasonable to delay RRSO until age 40 to 45 in this population if they have taken other steps to maximize breast cancer prevention (ie, bilateral mastectomy).36
Continue to: Adverse effects of RRSO...