BRCA Testing Must Expand Beyond Family History to Guide PARP Inhibitor Therapy in Ovarian Cancer
This review makes the case that germline BRCA testing should be offered to all women with high-grade serous ovarian cancer, not just those with family history, since nearly 20% harbour BRCA mutations and over 40% of these would be missed by history-based screening. BRCA status is now an established predictive biomarker for PARP inhibitor response, making universal testing essential for treatment decisions. For molecular diagnostics labs, this represented a paradigm shift toward reflex BRCA testing at diagnosis, with broader HRD biomarker panels on the horizon.
The original study
Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer.
- Authors
- George A, Kaye S, Banerjee S
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Review, Research Support, Non-U.S. Gov't
- PMID
- 27958297
Original abstract
The treatment of patients with ovarian cancer is rapidly changing following the success of poly [ADP-ribose] polymerase (PARP) inhibitors in clinical trials. Olaparib is the first PARP inhibitor to be approved by the EMA and FDA for BRCA-mutated ovarian cancer. Germ line BRCA mutation status is now established as a predictive biomarker of potential benefit from treatment with a PARP inhibitor; therefore, knowledge of the BRCA status of an individual patient with ovarian cancer is essential, in order to guide treatment decisions. BRCA testing was previously offered only to women with a family or personal history of breast and/or ovarian cancer; however, almost 20% of women with high-grade serous ovarian cancer are now recognized to harbour a germ line BRCA mutation, and of these, >40% might not have a family history of cancer and would not have received BRCA testing. A strategy to enable more widespread implementation of BRCA testing in routine care is, therefore, necessary. In this Review, we summarize data from key clinical trials of PARP inhibitors and discuss how to integrate these agents into the current treatment landscape of ovarian cancer. The validity of germ line BRCA testing and other promising biomarkers of homologous-recombination deficiency will also be discussed.