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How to Make Sense of Genetic Testing for Breast Cancer

OCTOBER 29, 2019
Clinical Congress Daily Highlights, Tuesday Second Edition


More and more, surgeons counsel patients on their genetic risk for breast cancer. On Tuesday, surgeons attending Clinical Congress got their own counseling, from a panel of breast cancer experts who discussed strategies to better understand genetic results and their impact on treatment decisions.

Laura Kruper, MD, MS, City of Hope Comprehensive Cancer Center, Duarte, CA, highlighted the underuse of genetic testing. “I remember the days when even a single genetic test used to be $4,000,” she said. But given the precipitous drop in the price of the technology, it now often costs as little as $250 for a full multi-gene panel. “One study has even shown that genetic testing for all women with breast cancer is cost-effective,” she observed, and encouraged appropriate testing for more patients.

This year, the National Comprehensive Cancer Network (NCCN) updated its criteria for genetic risk evaluation. But even with these updates not enough patients are being tested, according to a study Dr. Kruper discussed. About 8 percent of the 1,000 patients with breast cancer in this study had variants on an 80-gene panel that were likely or definitely pathogenic — even though half did not meet the NCCN criteria for gene testing. “Many of the patients with these variants would be eligible for clinical trials,” she noted. The American Society for Breast Surgeons has since issued its own guidelines, which allow physicians more flexibility to make individualized decisions based on patient characteristics.

A common theme among the presentations was how to deal with variants of uncertain significance (VUS). The consensus? Surgeons give them too much weight. Dr. Kruper cited a 2017 survey showing that up to half of breast cancer surgeons didn't make distinctions between a known pathogenic variant and a VUS when it came to treatment recommendations. She applauded the American Society for Breast Surgeons guidelines for making it clear that these variants are not clinically significant and should not be used to guide prophylactic surgical decisions.

Doreen Agnese, MD, The Ohio State University Wexner Medical Center, Columbus, added a 2015 survey to the discussion. This study of breast cancer specialists in the UK found that over 70 percent were unsure of the clinical implications of genetic testing results and didn’t know how to communicate the implications to their patients. Dr. Agnese pointed out the potential for over- or mistreatment.

On a 25-gene panel, at least one VUS will be identified about 33 percent of the time. Family history should guide management, she noted, not the presence of a VUS. She cited multiple studies showing that VUSs are rarely reclassified as likely pathogenic.

Dr. Agnese offered audience members resources to help them interpret genetic testing results. Most laboratories that do genetic testing, she said, employ genetic counselors who physicians can speak with about results. Online resources such as ClinVar, which aggregates information about variants from genetic testing labs, and Polyphen, which predicts the impact of a variant on the structure and function of its protein, let physicians do their own research.

Patricia Cronin, MD, Mayo Clinic, Phoenix, AZ, enumerated the many surveillance strategies in breast cancer and stressed that the ideal choice of surveillance, from modality to timing to frequency, is based on patients’ genetic risk as well as their individual and family medical histories.

Dr. Cronin also discussed surgical options for patients and noted that the option of risk-reducing mastectomies should be discussed with all patients carrying moderate- to high-risk variants. But she agreed with the other panelists that, when it comes to patients with VUSs, family history becomes critical. For all patients, she urged the audience, consider age and risk over the coming five to 10 years, rather than lifetime risk, before recommending prophylactic surgery.

Additional Information:
The Panel Session, More Than BRCA: Genetic Testing for Breast Cancer 2019, was held Tuesday, October 29 at the American College of Surgeons Clinical Congress 2019 in San Francisco (program, webcast and audio information).