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Hereditary Cancer Risk Variants Found in Significant Subset of Metastatic Breast Cancer Patients

NEW YORK – Investigators from Johns Hopkins University School of Medicine and the Vanderbilt Ingram Cancer Center have demonstrated that there is a potential benefit to doing widespread hereditary cancer risk testing in individuals with metastatic breast cancer.

"[O]ur 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," corresponding author Ben Ho Park, a hematology researcher at Vanderbilt, and his colleagues wrote in a research letter appearing in JAMA Oncology yesterday.

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. 

"[A] recent study found 11.8 percent of otherwise unselected patients with metastatic prostate cancer harbored a [pathogenic/likely pathogenic] germline variant, leading to a change in NCCN guidelines recommending germline testing for all patients with metastatic prostate cancer," the authors explained. "However, to our knowledge, analogous studies to quantify the prevalence of [pathogenic/likely pathogenic] variants among patients with metastatic breast cancer have not been performed." 

As they reported in JAMA Oncology, the researchers used a multigene germline panel test from Color 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 National Comprehensive Cancer Network'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 researchers found another 21 metastatic breast cancer patients who had variants of uncertain significance in one or more of the genes on the panel.

"[G]iven that many of the genes included on the multigene panel are involved in DNA repair," the authors further noted, "there is scientific rationale that some of these [pathogenic or likely pathogenic] variants (ATM, BRIP1, CHEK2) may also be predictive for response to PARP inhibitors, a hypothesis currently being tested in clinical trials."