Pathogenic Germline Variants Found in Breast Cancer Patients

There is still considerable debate on the value of multigene panel testing for inherited cancer in patients with breast cancer, based on both the prevalence of pathogenic/likely pathogenic (P/LP) variants and any therapeutic implications from genetic test results.

Recent studies demonstrate that the prevalence of P/LP variants is similar in patients with breast cancer whether or not they meet criteria for testing by the National Comprehensive Cancer Network (NCCN) guidelines. However, most participants in these studies were patients with early stage breast cancer and many low-risk variants were identified, raising the question of clinical actionability.


Scientists from Johns Hopkins University School of Medicine, Baltimore, MD, USA) and the Vanderbilt Ingram Cancer Center, Nashville, TN, USA) have demonstrated that there is a potential benefit to doing widespread hereditary cancer risk testing in individuals with metastatic breast cancer. Along with information for family members, the team reasoned that such testing might be beneficial for guiding treatment decisions in some metastatic breast cancer patients, particularly individuals carrying risky mutations in BRCA1 or BRCA2 who might be eligible to receive PARP inhibitor treatment.

The oncologists used a multigene germline panel test from Color Genomics (Burlingame, CA, USA) to prospectively search for pathogenic or likely pathogenic variants in 30 genes in 100 individuals with metastatic breast cancer, regardless of whether they met the NCCN’s testing criteria at the time. The team reported pathogenic or likely pathogenic variants in 14 of the 100 individuals, including six patients who did not meet NCCN testing guidelines. Conversely, two of the six metastatic breast cancer patients who carried risky BRCA1/2 mutations had not been tested in the past even though they did meet testing criteria from NCCN.

In addition to the pathogenic and likely pathogenic changes found in cancer-related genes such as ATM, BRIP1, or CHEK2, the scientists found another 21 metastatic breast cancer patients who had variants of uncertain significance in one or more of the genes on the panel. Ben Ho Park, MD, PhD, a Professor of Medicine and senior author of the study, said, “Our results 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 pathogenic or likely pathogenic variants that could have therapeutic implications.” The study was published on August 29, 2019, in the journal JAMA Oncology.

Related Links:
Johns Hopkins University School of Medicine
Vanderbilt Ingram Cancer Center
Color Genomics