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Breast Cancer Gene Screening Guidelines Miss Many Women at Risk

Samson, Kurt

doi: 10.1097/
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breast cancer; gene screening
breast cancer; gene screening:
breast cancer; gene screening

ORLANDO, FL—Almost half of women with high-risk genetic breast cancer mutations would not be eligible for genetic testing under existing National Comprehensive Cancer Network (NCCN) or Medicare criteria, according to two studies presented at the American Society of Breast Surgeons (ASBrS) Annual Meeting.

In the first research study, Dallas breast cancer surgeon Peter Beitsch, MD, of the TME Breast Care Network, told a press briefing that current economically based genetic testing guidelines exclude many patients who harbor high-risk breast cancer mutations and these standards “should be abolished immediately” (Abstract 402910).

He presented early findings from the group's Universal Genetic Testing Registry of breast cancer patients with no prior genetic testing. Data on 235 subjects showed that, while 10 percent had genetic mutations linked to breast cancer under NCCN criteria, almost 9 percent did not.

The community-based network, started in 2016, is a collaboration between TME Research and Invitae Corp. Subjects are tested using Invitae's multi-cancer panel, an 80-gene test that includes genes associated with hereditary cancers in eight major organ systems.

To date, the test results show no statistically significant difference between patients with pathological or likely pathological (P/LP) mutations who met NCCN guidelines and those who did not.

The Universal Genetic Testing Registry target accrual is 1,000 patients, with 500 who meet and 500 who do not meet NCCN testing guidelines. With 923 subjects enrolled to date, 713 women have completed testing and data on 364 patients has been reviewed.

Of these, 48 percent met NCCN criteria and 52 percent did not. Among those who met genetic testing criteria, 10.2 percent had pathogenic or likely pathogenic variants, while 8.6 percent did not, and 60.8 percent had been recently diagnosed with breast cancer. In these women, 46.6 percent met NCCN criteria and 53.3 percent did not. Of patients who had been recently diagnosed, 49.7 percent met NCCN criteria and 50.3 percent did not. In all, 11 percent of the women had a prior diagnosis of non-breast cancer and, among them, 46.3 percent met NCCN criteria and 53.7 percent did not.

“Current guidelines are detrimental to identifying patients with P/LP mutations and should be abandoned,” said Beitsch, former president of ASBrS. “There is no statistically significant difference between the pathogenic variant rate between patients who meet and who do not meet NCCN guidelines. The cost of expanded panel genetic testing has decreased to the point that economically based guidelines for testing are no longer relevant.”

He said the current NCCN guidelines were established prior to today's more sophisticated BRCA1/2 and multi-gene testing, and most insurance carriers base their coverage on the guidelines and usually only recommending testing for BRCA1/2.

“The guidelines were set up to really be an economic roadblock back in the day. They were set up to discover BRCA1 and BRCA2 mutation patients at a certain percentage back when the test was $5,000 per test,” he said, noting that test costs have come down to $250 or lower. “The time has come to bring guidelines up to date with recent genetic findings.”

Expanded panel testing yields more pathogenic hereditary mutations than tests for BRCA 1/2 or breast cancer panels with 5-7 genes, he said. And, in addition to identifying more women with breast cancer variants, universal genetic testing of women will reveal a more complete “genetic fingerprint” for breast cancer research.

Among women who met NCCN criteria, 12.4 percent had a P/LP mutation, while 11.5 percent who did not meet the criteria had a pathogenic mutation, a difference that was not statistically significant, and the spectrum of mutations varied between both groups with some overlap.

“Women do not need to be protected from their genetic health information,” Beitch told the group. “Genetic testing is the future of medicine, not just in patients with cancer but all patients.”

Similar Medicare Findings

In the second study, almost half of Medicare patients with actionable genetic variants for breast cancers do not meet current criteria (Abstract 404340).

Jennifer Axilbund, MS, a counselor with Invitae, reviewed a consecutive series of Medicare patients identified for testing due to a personal and/or family history of breast and/or gynecological cancer, and where BRCA1 and BRCA2 genes were involved.

Study findings came from clinicians who completed a brief checklist indicating whether patients did or did not meet Medicare criteria for BRCA1/2 genetic testing. Genetic test outcomes were next compared between the in-criteria and out-of-criteria groups for different sets of genes.

While 76.2 percent met BRCA1/2 guidelines, 23.8 percent did not, she found. Moreover, there was no statistical difference between patients testing positive for BRCA1/2 variants and whether or not they were qualified under Medicare (3.3% vs. 2.2%). Screening for other breast cancer-related mutations showed similar parallels (9.6% vs. 7.8%).

“Under Medicare criteria, almost half of all patients with actionable variant genes are missed,” Axilbund said.

Patients who met Medicare screening criteria had a 10.2 percent pathogenic/likely pathogenic variant rate (36/353), while the rate for those who did not was 8.6 percent (31/360).

Both investigators agreed that, as expected, screening criteria are more effective for women who carry highly penetrant BRCA1/2 mutations than other mutations.

“The current criteria specifically reflect the historically severe presentation of high-penetrant BRCA1/2 variants, and do not adequately capture the range of clinical presentations commonly seen,” said Axilbund. “Carriers of clinically actionable variants in genes other than BRCA1/2 are just as likely to fall outside of current criteria.”


Judy C. Boughey, MD, a breast cancer surgeon at Mayo Clinic in Rochester, Minn., and ASBrS Publications Committee Chair, said the two studies highlight the importance of discussing genetic testing with patients diagnosed with breast cancer.

“With the advances in panel testing for predisposition genes, the likelihood of identifying a pathogenic or likely pathogenic mutation are higher, at around 8-10 percent in these two studies,” she said. “However, we must remember that not all mutations are medically actionable. When evaluating genetic testing, we should consider the likelihood of identification of a mutation, cost of testing, and potential impact of the result on medical management.”

Stephen R. Grobmyer, MD, FACS, the Lula Zapis Endowed Chair and Professor of Surgery at Lerner College of Medicine, and co-leader of the Cleveland Clinic Comprehensive Breast Cancer Program, said research confirms that multigene panel testing identifies more actionable mutations than BRCA1/2 testing alone in newly diagnosed breast cancer patients.

“These studies raise the issue as to whether current guidelines for performing germline genetic testing in newly diagnosed breast cancer patients are too restrictive.”

Grobmyer cited a recent study by his research group that found multigene panel testing identified actionable mutations in approximately 20 percent of tested patients with triple-negative breast cancer compared to approximately 8 percent in triple-negative breast cancer patients screened for BRCA1/2 testing alone (J Am Coll Surg 2018;226:560-565).

“I think studies such as these should be taken into account when new versions of the guidelines are developed,” he noted. “Detailed information from these studies certainly could help make future versions of the guidelines more useful for guiding and improving patient care. Also, insurers and CMS rely on guidelines as criteria for genetic testing. I anticipate as experts agree on new criteria that [they] will follow in expanding their testing criteria.”

It is very also important to improve provider and patient education, Grobmyer told Oncology Times.

“Numerous studies have documented that among patients who meet current guidelines for genetic testing, a large percentage are not referred for genetic testing. This represents a significant opportunity for improving care for the newly diagnosed.”

Kurt Samson is a contributing writer.

Wolters Kluwer Health, Inc. All rights reserved.
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