Debate examines pros and cons of genetic testing for all BCa patients


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4 minutes
Mark Robson, MD
Mark Robson, MD

Should all breast cancer patients have germline genetic testing? That is a question getting a lot of attention and, while a number of recent guidelines suggest that genetic testing should be made available to all breast cancer patients, there are concerns regarding the challenges and clinical implications imposed by universal testing. A pair of expert clinician-scientists discussed the benefits and the potential drawbacks of universal genetic testing during a Virtual SABCS debate on Friday, Dec. 11.

Looking at the benefits of testing for all breast cancer patients, Mark Robson, MD, Chief of Breast Medicine Service at Memorial Sloan Kettering Cancer Center, said that it basically comes down to the question of clinical utility — a question that was not immediately clear in the early days of genetic testing for breast cancer.

“Initially, we believed that mutations — what we now consider pathogenic variants — in BRCA1 and BRCA2 in particular were rare, but that they conferred a very high risk for developing cancer,” Dr. Robson said. “There was not thought to be any particular therapeutic benefit to identifying pathogenic variants and, at the time that we began this, preventive interventions such as prophylactic mastectomy or preventive salpingo-oophorectomy were also unproven.”

Fast forward to today, he said, and it has become clear that BRCA1, BRCA2, and likely PALB2 as well have robust clinical utility for newly diagnosed patients who are candidates for and willing to entertain contralateral prophylactic mastectomy.

“It also has robust clinical utility for patients with breast cancer who are potentially candidates for risk-reducing salpingo-oophorectomy,” Dr. Robson said. “This doesn’t apply so much to PALB2 since the ovarian cancer risk does not appear to be significantly elevated. But certainly for BRCA1 and BRCA2, identifying individuals who could potentially develop ovarian cancer is an important factor, and it also has robust clinical utility for patients with metastatic disease who are eligible for PARP inhibitors.”

In these groups of individuals, particularly those under the age of 60-65, Dr. Robson said if they are deciding about preventive surgery and if they have metastatic disease, a policy of unselected testing for BRCA1, BRCA2, and PALB2 could be important.

“On the other hand, identifying these genes would have familial benefit regardless of the clinical utility for the individual being tested, assuming that there either are or would be females at risk in the family who would be willing to consider testing and subsequent action, or males who would be willing to potentially communicate that information to future generations,” he said.

Susan Domchek, MD
Susan Domchek, MD

On the other side of the question, Susan Domchek, MD, Director of the Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, talked about criteria for who should be tested and what the threshold of detection of pathogenic variants should be to either “mandate” or “offer” testing.

“I do think that wording matters, because offering testing or discussing the option of testing with someone is very different than saying it’s the standard of care for every single patient to always get testing,” Dr. Domchek said.

When looking at the question of who should be tested in the context of the ongoing philosophical debate in health care about “doing less” and “doing more,” she said it’s important to remember that clinical utility is the gold standard.

“That means by adding something to someone’s care, we help improve their care and we help improve their outcomes, and so in this framework, we really have to think about how much additional benefit we’re getting out of the things that we do,” Dr. Domchek said.

Risk stratification and which genes to include, she said, remain important considerations in genetic testing.

“Maybe we do test all women under 60 and then risk stratify after that,” she said. “But I would also say that testing for BRCA1, BRCA2, and PALB2 is reasonable, but we have to realize that we’ll miss very few people with mutations in these genes with current criteria, and it’s similar to what is found in population screening.”

Additionally, she said it’s important to remember that testing everyone is not risk free, noting the inappropriate management of variants of uncertain significance (VUS) as an example.

“More genes is not better — we see inappropriate management of pathogenic variants in moderate penetrance genes, and we have uncertainty regarding clinical utility in the absence of family history,” Dr. Domchek said. “And no matter what we do, we need to keep an eye on disparities since we know they exist already.”

SABCS registrants have exclusive on-demand access to this and other virtual SABCS programming until March 13, 2021.