Talazoparib, an orally available polyadenosine diphosphate-ribose polymerase (PARP) inhibitor developed by Pfizer was approved by the Food and Drug Administration (FDA) in 2018 for the treatment of advanced metastatic breast cancer with human epidermal growth factor receptor 2 (HER2/ERBB2)-negative breast cancer with germline BRCA1 and BRCA2 (BRCA) pathogenic variants. Germline BRCA mutations may produce hereditary breast cancer syndrome.

Studies have shown the prevalence of pathogenic/likely pathogenic variants in patients with breast cancer whether they meet the National Comprehensive Cancer Network (NCCN) testing guidelines or not, raising questions if this finding has clinical relevance. The NCCN guidelines have previously not suggested multigene panel testing for inherited cancer patients.

A new study published on August 29 in JAMA Oncology, found that 11.8% of unselected patients with metastatic prostate cancer harbored a P/LP germline variant. In the study, 100 patients were tested, whether they met NCCN guidelines or not. Among the 14 patients who did test positive for a pathogenic or likely pathogenic variant, 43% did not meet the NCCN guidelines. This led to a change in NCCN guidelines recommending germline testing for all patients with metastatic prostate cancer. A similar study has not been conducted to quantify the prevalence of P/LP variants among patients with metastatic breast cancer.

However, the authors question if the NCCN guidelines need to be modified for testing in breast cancer patients, given that talazoparib has recently been approved and could be used as a targeted therapy in these patients. If patients are not tested, they may be missing out on this treatment option.

Participants in the study included 76 white patients, 12 black patients, six Asian patients, three Hispanic patients and three of other racial/ethnic identification. Two of the patients were male.

"We found almost twice as many mutations than what we would have found if we adhered to NCCN guidelines, and some of those patients could go on clinical trials that could therapeutically help their disease," said senior author, Ben Ho Park, MD, PhD, Donna S. Hall Professor of Breast Cancer Research at Vanderbilt University Medical Center and co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center.

Do you have a unique perspective on your research related tocancer research? The Science Advisory Board wants to highlight your research. Contact the editor today to learn more.