Other cancers in BRCA1 and BRCA2 mutation carriers: implications for counselling and follow up

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Data come from the Breast Cancer Linkage Consortium. The BRCA1 estimates (from 1993) are being updated. The overall risk of ovarian cancer was estimated as 30% by age 60 (but the data suggested the possibility, subsequently supported by mutation data, of heterogeneity, with two groups of families with higher and lower risks of ovarian cancer), and 3- and 4-fold increases in risk of prostate and colorectal cancer respectively, corresponding to absolute risks of about 5-10% by age 70. The BRCA2 estimates are more recent and so based on more extensive data. The estimated cumulative risk of ovarian cancer is 0.4% by age 50 and 27% by age 70 (again with evidence of heterogeneity from mutation studies); statistically significant elevated risks are also observed for prostate cancer (overall RR 4.65 [7.33 below age 65]; absolute risk 7.5% by age 70); pancreatic cancer (RR 3.51 [5.54 below age 65]; absolute risk 2% by age 70), gall bladder and biliary cancer (RR 4.97), stomach cancer (RR 2.59), malignant melanoma (RR 2.58) and cancer of the oropharynx (RR 2.26, 95% CI 1.09-4.58). There was no significant increase in risk of colorectal cancer. The estimated cumulative risk of male breast cancer is 2% by age 70, but with very wide confidence limits.

These overall risks will differ in individual cases according to the specific BRCA mutation, and genetic and non-genetic modifiers. Except possibly for the protective effects of OC use on ovarian cancer, this information is not ready to be translated into clinical practice. The main controversy is around screening for colorectal and prostate cancer. The balance of risks and benefits is not known for either; there is no consensus; a BCLC study of prostate screening is proposed and a colorectal study in BRCA1 carriers may be appropriate if the risks are confirmed.