Ovarian and fallopian tube cancer
Apart from BRCA1 and BRCA2 there are no studies focused on the utility of risk-reducing salpingo-oophorectomy (RRSO) in women with a pathogenic variant in a gene that increases the risk of epithelial ovarian cancer. However, in a UK setting, premenopausal RRSO is cost effective at ≥4% lifetime ovarian cancer risk.r
The current evidence is insufficient to make a firm recommendation as to the optimal age for RRSO in women with a pathogenic variant in a non-BRCA ovarian cancer risk gene. Based on the current limited evidence base, a discussion about surgery should be held around age 45 years and after family completion, or earlier if there is a family history of an earlier onset ovarian cancer.rr
For women at increased risk because of a family history of ovarian cancer the age at which RRSO is recommended should be individualised. Factors to consider include residual age-related ovarian cancer risk, the impact of oophorectomy on fertility, co-morbidities, family history and personal preference.
The effectiveness and safety of risk-reducing bilateral salpingectomy followed by delayed bilateral oophorectomy has not been established, and it is not recommended for ovarian cancer risk management.
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. Effective ovarian cancer risk management relies on RRSO.
Although there is evidence that the combined oral contraceptive pill can reduce ovarian cancer risk, it is significantly less effective than RRSO and it is not recommended for cancer prevention.
Estimating ovarian cancer risk
Currently there is no independently validated family history based tool for estimating ovarian cancer risk.
Jervis et al. (2015)r developed an ovarian cancer risk prediction model that is incorporated into BOADICEA and the CanRisk Web Tool (which utilises BOADICEA version 5). Familial cancer services that use BOADICEA/CanRisk should be aware BOADICEA is validated for breast cancer risk, but has not been independently validated for ovarian cancer risk. In addition, BOADICEA versions 4 and earlier considered only the effects of BRCA1 and BRCA2 on ovarian cancer risk and are not appropriate outside BRCA1 and BRCA2 families. BOADICEA version 5 uses a model that includes the effects of pathogenic variants in BRCA1, BRCA2, RAD51D, RAD51C and BRIP1, polygenic risk scores, residual family history, and personal lifestyle/hormonal/reproductive risk factors.
Other cancer risks
Many, but not all, genes that are associated with an increased risk of ovarian cancer are also associated with a risk of other cancers.
^ MMR - mismatch repair
^^ EPCAM refers to a deletion in EPCAM affecting MSH2 function
¶ Cumulative breast cancer risk is influenced by family history; some carriers will be close to population risk for breast cancer