All Patients With Metastatic Breast Cancer Should Undergo Germline Testing, Study Finds

In In The News by Barbara Jacoby

By: Laura Joszt


All patients with metastatic breast cancer should undergo genetic testing, according to a new study on the prevalence of pathogenic/likely pathogenic (P/LP) variants in patients with metastatic breast cancer.

The results, published in JAMA Oncology, highlight that there is a high prevalence of P/LP variants among the group of patients with metastatic breast cancer, which could have therapeutic implications since the FDA has approved polyadenosine diphosphate–ribose polymerase (PARP) inhibitors for patients with metastatic human epidermal growth factor receptor 2-negative breast cancer with germline BRCA1 and BRCA2 pathogenic variants.

Researchers at Johns Hopkins University School of Medicine and the Vanderbilt Ingram Cancer Center performed germline testing on 100 patients with metastatic breast cancer using a panel of 30 genes. They found 14 patients had the P/LP variant and 21 had a variant of unknown significance.

Nearly half (43%) of the patients with P/LP variants actually did not meet the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing. In addition, 2 of the 6 patients with P/LP BRCA variants had never received genetic testing.

“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,” senior author, Ben Ho Park, MD, PhD, the Donna S. Hall Chair in Breast Cancer at Vanderbilt University Medical Center and coleader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center, said in a statement.

The authors noted that their study is limited by the small sample size, and they had excluded patients who had prior germline testing unless the patient had results that were negative for 10 or fewer genes.

Some of the P/LP variants may be able to predict responses to PARP inhibitors, the authors wrote, which means the study’s findings “provide evidence to support genetic testing for inherited cancer predisposition among all patients with metastatic breast cancer because this group represents a population with a high prevalence of P/LP variants that could have therapeutic implications.”


Stuttgen K, Croessmann S, Fetting J, et al. Pathogenic germline variants in patients with metastatic breast cancer [published online August 26, 2019]. JAMA Oncol.  doi:10.1001/jamaoncol.2019.3116.