Bilateral risk-reducing mastectomy reduces cancer risk by at least 90%rr (depending on the operation performed). Statistically significant survival benefit associated with bilateral risk-reducing mastectomy compared with surveillance is yet to be demonstrated.
While RRSO had been reported to reduce breast cancer risk by 53% in BRCA1 and BRCA2 pathogenic variant carriers,r this protective effect has been questioned, with a prospective study showing no reduction in breast cancer risk in BRCA1 pathogenic variant carriers with RRSO.r Recent data indicates the benefit for BRCA2 pathogenic variant carriers is restricted to the risk of breast cancer diagnosed before the age of 50.r
MRI is the preferred screening technique due to its high sensitivity compared with MMG or US. The addition of MMG is limited, and does not lead to a significant increase in sensitivity compared with MRI alone.r There is no added value of ultrasound in women undergoing MRI for screening. MRI detects tumours which are smaller and more likely to be node-negative than MMG. MRI has a recall rate (requiring further investigation and/or biopsy) of 15% for initial screening, which decreases with subsequent rounds of screening to <10%.
Mammography screening is not recommended before age 40 years in BRCA1 and BRCA2 pathogenic variant carriers. The sensitivity of MRI is not influenced by age or breast density, being similar in women aged >50 years to those aged <50 years. On current evidence, it may be reasonable to offer breast MRI to women with BRCA1 and BRCA2 pathogenic variants beyond age 50 years.r
The rate of cancers occurring between annual screening (interval cancers) is higher in BRCA1 pathogenic variant carriers than other high risk populations.
Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high risk women. To date studies have not included enough BRCA1 or BRCA2 pathogenic variant carriers to determine if it is effective for primary prevention in this population. Tamoxifen use is associated with a reduction in contralateral breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers with breast cancer; such benefit is stronger if ovaries are still intact.r In view of the potential side effects associated with tamoxifen/raloxifene, risk-reducing medications should be discussed with an experienced medical professional to determine the relevant risks and benefits in an individual pathogenic variant carrier. See COSA medication to lower the risk of breast cancer: clinician guide.
Ovarian and fallopian tube cancer
Bilateral risk-reducing salpingo-oophorectomy (RRSO) significantly reduces the risk of ovarian and fallopian tube cancer in BRCA1 and BRCA2 pathogenic variant carriers.r The residual risk of primary peritoneal cancer after RRSO is <2%.r
The effectiveness and safety of risk-reducing bilateral salpingectomy followed by delayed bilateral oophorectomy has not been established, and is not recommended for ovarian cancer risk management.
The decision to perform hysterectomy at the time of RRSO should be individualised. There is no evidence of an increased risk of endometrial cancer in Australian BRCA1 and BRCA2 pathogenic variant carriers, although there is some evidence that serous histology may be more common in BRCA1 pathogenic variant carriers.rr Hysterectomy may simplify subsequent menopausal hormone therapy, or the use of tamoxifen for breast cancer risk or as adjuvant treatment of breast cancer, but it is not justified for endometrial cancer prevention alone.
For asymptomatic women annual transvaginal ultrasound (TVU) and serum CA125 levels have poor sensitivity and specificity for ovarian cancer. They do not reliably detect ovarian cancers at an early stage, nor do they affect outcomes. This is true of women in the general population and women at high risk of hereditary ovarian cancer. Effective ovarian cancer risk management relies on RRSO.
Although there is evidence that the combined oral contraceptive pill can reduce the ovarian cancer risk, it is significantly less effective than RRSO and it is not recommended for cancer prevention.
There is currently no effective surveillance that detects early pancreatic cancer.