Costs and benefits of tumour testing to improve cancer prevention and survival

Women who inherit a BRCA gene mutation are at high risk for breast cancer and the most lethal type of ovarian cancer, high-grade serous ovarian carcinoma (HGSC).

A woman diagnosed with HGSC has a 20% chance of unknowingly carrying a BRCA mutation, and is eligible for genetic testing. Getting a blood sample to do genetic testing in this woman is critical, because if she is found to have a BRCA mutation: 1) her relatives (daughters, sisters) can be tested, and HGSC can be PREVENTED in them, and 2) she herself can be treated with PARP inhibitors that can improve survival.

The problem, however, is that the yield of genetic testing is low, and only 30% of women with HGSC undergo such genetic testing. This excludes 70% from effective treatment and leaves their family members at high risk. How can BRCA mutations be better identified?

One strategy is to begin with testing the HGSC tumour itself. If the tumour has a BRCA mutation, PARP inhibitor treatment can be given. These women can then be targeted for genetic testing, and 2/3 of them will have an inherited BRCA mutation. This improves the efficiency of genetic testing, rather than referring everyone with HGSC.

Tumour testing of HGSC is not routinely done in BC. Hence, I propose to conduct a pilot study of tumour testing for BRCA mutations in HGSC, and a cost-effectiveness analysis of its impact on ovarian cancer survival and future cancer prevention, to justify this testing in this patient population.