Highly penetrant gene variants in BRCA1 and BRCA2 genes are associated with increased risk of several cancers, particularly breast and ovarian. These show autosomal dominant inheritance pattern.1,3 Pathogenic variants in BRCA1 and BRCA2 are associated with increased risk of other cancers including prostate (for men specifically) and pancreatic.
The lifetime risk of breast cancer in Australian women is approximately one in eight.4 Inheriting pathogenic variants of the BRCA1 and BRCA2 genes increase the chance of developing breast cancer to about 70% (cumulative risk to 80 years of age). Despite this, BRCA1 and BRCA2 variants account for only about 5% of all breast cancer cases, because these variants are relatively rare.3–6
Several other genes (low-to-moderate penetrant variants) predisposing to breast and/or ovarian cancer can now also be tested.7
Features within a family that are suggestive of increased risk of carrying a pathogenic BRCA1 or BRCA2 variant include:5
- multiple affected relatives on the same side of the family (maternal or paternal)
- breast and ovarian cancer in the same woman
- breast cancer diagnosed <40 years of age
- Ashkenazi Jewish ancestry (from central and eastern Europe)
- bilateral breast cancer
- male breast cancer.
A three-generation family history is key to identifying high-risk families who are most likely to benefit from genetic testing. Such a history should include first-degree and second-degree relatives on both sides of the family, and ethnic background (eg Ashkenazi Jewish). Note that sex-specific cancer can be inherited through maternal or paternal sides of the family (eg BRCA variants can be passed from the paternal side). Type of cancer (including bilateral) and age of onset should be recorded where available.4
Use existing risk criteria to identify families who are at increased risk of carrying a pathogenic BRCA1 or BRCA2 variant (high risk), or women who may require additional screening or chemoprevention (moderately increased risk).2
Alternatively, the ‘Familial risk assessment – Breast and ovarian cancer’ (FRA-BOC) tool can be used to assess risk .8