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NSGC Panel Divided on Whether Newly Diagnosed Breast Cancer Patients Should Undergo Panel Testing


SALT LAKE CITY – Experts are divided on whether all newly diagnosed breast cancer patients should undergo multi-gene panel genetic testing and whether that testing should focus on highly penetrant genes or encompass a broader set of risk-conferring genes.

Earlier this year, the American Society of Breast Surgeons updated its recommendations to urge multi-gene panel testing — with a particular focus on BRCA1, BRCA2, and PALB2 testing — of individuals diagnosed with breast cancer to gauge their hereditary cancer risk. Alterations in these genes could influence clinical decisions.

"We need the genetic testing results to make therapeutic decisions in our newly diagnosed patients, " David Euhus, the chief of breast surgery at Johns Hopkins Medicine who was on the panel that developed the new recommendations, said during a debate on Wednesday at the National Society of Genetic Counselors' annual meeting here. "It's important now for systemic therapy decisions like PARP inhibitors, platinum drugs, [and is] important for radiation therapy decisions." 

In the ensuing discussion, speakers called for increased testing of or at least knowledge of genetic testing by breast cancer patients, but another cautioned that the appropriateness of  testing could hinge in part on whether it is being used to guide clinical decisions in high risk patients or for population screening. The speakers also diverged on whether all newly diagnosed breast cancer patients should undergo multi-gene panel testing.

"There is not a clear answer," panel moderator Lisa Madlensky, a genetic counselor at the University of California, San Diego, said at the start of the debate.

Individuals with certain inherited mutations in BRCA1, BRCA2, and PALB2 are at increased risk for breast and other cancers, and hereditary mutations in these genes are increasingly being used to guide treatment. For instance, a PARP inhibitor therapy might be offered to patients with BRCA1 or BRCA2 mutations.

"I think when it comes to offering BRCA1, BRCA2, and PALB2 testing to all breast cancer patients, the clinical utility for the individuals who have mutations is pretty clear and the clinical utility for their family members is pretty clear,"Memorial Sloan Kettering Cancer Center's Mark Robson, a medical oncologist, said. "The benefit-to-harm ratio is probably favorable, assuming that there's an appropriate management of variants of uncertain significance and assuming that the individual themselves is not blindsided by the implications of the information."

But the situation is not as clear with other breast cancer risk-related genes. Alterations in genes like CHEK2, RAD50, and others have also been implicated in breast cancer risk, albeit at a more moderate penetrance, and these are included on multi-gene panel tests for hereditary breast cancer. 

Peter Beitsch, a surgeon at the Dallas Surgical Group, argued that including additional risk genes could lead to better outcomes for patients. He cited a cost-effectiveness study that appeared last month in JAMA Oncology from Queen Mary University of London's Ranjit Manchanda and colleagues that compared outcomes of unselected breast cancer patients or patients who met current family history- or other testing criteria who underwent multi-gene panel testing for BRCA1, BRCA2, and PALB2. They found that one year of unselected testing could prevent 2,101 cases of breast or ovarian cancer and 633 deaths in the UK and 9,733 cases and 2,406 deaths in the US.

"The best way to treat a cancer is to never get one," Beitsch said. "And this is how we're going to hopefully find out about that."

But Robson added that the genes included on a panel might encompass not only high-penetrance genes like BRCA1 and BRCA2, but also genes whose relevance to breast cancer is unclear or controversial. He noted that BRCA1 and BRCA2 testing of breast patients who are undergoing surgery could be considered a biomarker test as it influences surgical decision-making, such as who might be a candidate for salpingo-oophorectomy. However, these other genes are essentially being used as a population-screening tool, he said, and they are being mixed together in one test. He argued that the ratio of potential benefit to potential harm of such extended testing is unfavorable.

However, Sue Friedman, the executive director and founder of the patient advocacy organization Facing Our Risk of Cancer Empowered (FORCE), said testing of all actionable genes should be offered to all newly diagnosed patients alongside genetic counseling. She added that other genes could be included on testing panels, so long as they are labeled as experimental and patients give consent for their inclusion. "All people … who are diagnosed with breast cancer should know about the test," she said. "I certainly think everybody should know that a test exists [and] they should know about the benefits, limitations, and costs."

In practice, Robson pointed out that offering multi-gene panel testing to everyone as a matter of course could mean that the need for detailed consent is disregarded. He noted that with the adoption of universal immunohistochemistry screening in colon cancer, many patients are often unclear they are being tested for Lynch syndrome until they receive their results. He acknowledged, though, that the field appears to be moving toward multi-gene panel testing.

This, the panelists noted, underscores the need for better education of not only patients, but also physicians and other providers, and is an arena where genetic counselors might have a large impact.

"I think the surgeons need much stronger relationships with the genetic counselors, and I think education is important," Hopkins' Euhus said. 

"But my number one observation is that we need to cooperate together, and pool our efforts and our knowledge, to manage this changing paradigm," he added.