Current Testing Criteria Miss Breast Cancer Mutations

Women who do not meet breast cancer genetic testing criteria have a similar number of cancer-associated mutations as women who do meet the criteria, according to two separate studies presented at the American Society of Breast Surgeons meeting (Orlando, Fla.; May 2-6). In both studies, which evaluated differing criteria, the authors question the efficacy of existing clinical testing criteria, saying that actionable mutations likely remain undetected in women not meeting the current guidelines for testing.

In the first study Peter Beitsch, M.D., from TME Breast Cancer Network in Dallas, Texas, and colleagues showed that women are missed when the National Comprehensive Cancer Network (NCCN) guidelines are used.

The researchers created a community-based registry based on patients from 18 breast physicians experienced in cancer genetic testing and counseling. Participants underwent testing with an 80-gene panel test (InVitae Multi-Cancer Panel) to determine differences in the incidence of pathogenic and likely-pathogenic (P/LP) mutations based on meeting or not meeting NCCN testing criteria.

While the study has an accrual goal of 1,000 patients, these early results are for 235 patients with available genetic testing results. To date, 12.4 percent of patients who met NCCN criteria had test results with a P/LP mutation versus 11.5 percent of patients who did not meet criteria, but had a P/LP mutation. While the percentage of mutations was similar whether or not women met testing criteria, the detected variants varied by testing eligibility. BRCA1/2 and other common variants were more likely to be detected among women who met NCCN testing criteria, while women not meeting the criteria had a larger proportion of less common variants, but that still have guidelines for clinical management.

Beitsch reported that had the nonguideline-compliant patients been tested only for the 11 mutations recommended by NCCN, more than 40 percent of the detected variants would have been missed.

“Economically based guidelines for genetic testing of breast cancer patients are anachronistic, miss a significant number of pathogenic variants, and we believe they should be abolished immediately,” Beitsch said during a press briefing at the conference.

A second study similarly found that the rate of LP/P variants was similar among patients who did and did not meet criteria for BRCA1/2 genetic testing, but this group used Medicare criteria for genetic testing, which focuses on high-risk genes and requires the patient to have a cancer diagnosis.

Three-quarters of the 1,990 patients in the cohort met Medicare testing criteria. Positive results were similar between the groups regardless of whether just BRCA1/2 results were considered or whether all positive genetic mutations were considered. The researchers estimate that almost half of Medicare patients with actionable variants will be missed if testing is restricted to those meeting current Medicare testing criteria.

“These criteria do not adequately reflect evolving genetic knowledge, and they miss patients who should have increased cancer screening or should receive different systemic therapy,” said Jennifer Axilbund, from the genetic testing company Invitae. “Testing criteria should be broadened to include unaffected individuals with a positive family history and affected individuals with less severe presentation.”

Takeaway: Analysis reveals that women who do not meet two different breast cancer genetic testing criteria still have a similar number of cancer-associated mutations to women who do meet the criteria.