Multigene Sequencing Rapidly Replacing BRCA Tests

Roxanne Nelson, BSN, RN

May 14, 2018

An increasing number of women who are diagnosed with breast cancer are opting for multigene sequencing instead of the more limited testing for only BRCA1/2 mutations, according to a new report.

The findings come from the ICanCAre study, published online May 10 in JAMA Oncology, which followed about 5000 women who had been diagnosed with stage 0-II breast cancer from 2013 to 2015.

About one quarter of these women underwent genetic testing of any kind. This number remained relatively constant throughout the 2-year study period. Among those who were tested, the proportion who underwent multigene testing steadily rose at a considerable rate.

About 26% of patients underwent multigene testing in 2013, but this percentage jumped to 66% within 2 years. In contrast, the percentage of women opting for BRCA-only testing declined from about 74% to 34% during the same period.

Dr Allison Kurian

"In general, multigene panel tests yield more clinically useful results and are rapidly becoming the norm," said lead Allison Kurian, MD, associate professor of medicine and of health research and policy at Stanford University School of Medicine in California, in a statement.

"Newly diagnosed women should ask their doctors whether they may be appropriate candidates for genetic testing. They should also advocate for the opportunity to discuss genetic testing and its implications with an experienced clinician, such as a genetic counselor, in a timely manner," she said.

Whereas previously, the only cancer-related genes that were routinely sequenced were BRCA1/2, panels are now available that can sequence up to 90 genes. But multigene sequencing is still quite new, and not much is known about the implications of such sequencing, Kurian commented in an author interview posted on the JAMA Oncology website.

"Before 2013, it really wasn't done very much, but since then, it has become more common, thanks to advances in technology and changes in patent law that made it easier to test more genes at a lower price," she said

Following a protracted legal challenge over the right to patent the BRCA1 and BRCA2 genes, Myriad Genetics lost its battle in 2013, when the US Supreme Court ruled against the company. The Supreme Court decision effectively removed Myriad's monopoly on BRCA genetic testing, which subsequently led to markedly lower costs of multigene sequencing for assessing breast cancer risk.

The ICanCare study began enrollment about a month later, with the goal of evaluating the uptake and outcomes of multigene sequencing in a large, contemporary cohort of breast cancer patients.

Women from Surveillance, Epidemiology, and End Results Program (SEER) registries across Georgia and in Los Angeles, California, were surveyed, and the SEER data and results of clinical genetic testing (provided by four laboratories) were merged. The analysis included a racially diverse cohort of 5026 women. Of those patients, results of any kind of genetic testing were available for 1316 (26.2%); results of multigene sequencing were available for 588 patients; and results of BRCA1/2 testing were available for 728 patients.

The authors note that there was a substantial change in the type of test that was selected, with multigene sequencing increasingly replacing BRCA1/2-only testing. During the 2-year study period, the rate of multigene sequencing rose from 4.8% to 19.6%, while BRCA1/2-only testing dropped from 22.6% to 10.0%.

Discussion and Timing

Participants were asked about their experiences with testing. Genetic counselors were more likely to order multigene sequencing (25.5% vs 15.3%; P < .001), whereas surgeons frequently ordered both types of tests.

Most testing was conducted prior to surgery, but women who underwent multigene sequencing were more likely to report that testing was delayed until after surgery (32.5% vs 19.9% for BRCA1/2-only testing; P < .001).

More genetic counselors are needed, and they should be integrated into routine cancer care. Dr Allison Kurian

Interpretation of multigene panels is more complex and requires the expertise of genetic counselors, who are not always readily available, which could be partly responsible for the delay. "As genetic testing has become more comprehensive and less expensive, we have begun to see a significant problem in terms of the genetic-counselor workforce," Kurian said. "More genetic counselors are needed, and they should be integrated into routine cancer care. There is also a need for new care-delivery models that effectively triage appropriate patients to timely genetic counseling."

Senior author Steven Katz, MD, MPH, professor of medicine and of health management and policy at the University of Michigan, Ann Arbor, pointed out that "patients and their clinicians may view genetic testing as a lower priority than tumor biology and pathology testing, which most directly inform the treatment options."

Future Steps

"There is a need for advances in care delivery, to think about ways to get patients more promptly counseled and tested after their diagnosis," Kurian said in the author interview. "There is a high rate of uncertain results that is much higher in racial/ethnic minorities, and it's a big problem and means that we should be addressing research for that so the results can be more clinically useful."

Although the authors did not find strong evidence that women who underwent multigene testing were more likely to undergo more extensive surgery, such as a double mastectomy, Kurian noted that "we are looking at the long-term clinical impact on decision making."

Currently, a larger study is being conducted to assess the test results of breast and ovarian cancer patients, which will inform some of these issues. "We need to look more at what care happens after the test results," she said. "We need to do further surveying, not only of patients but also their clinicians and their relatives, because these have strong implications for their relatives as well."

The research was supported by the National Institutes of Health, the National Cancer Institute, and the University of Michigan Cancer Center. Stanford Univerity's Departments of Medicine and of Health Research and Policy also supported the study.

JAMA Oncol. Published online May 10, 2018. Full text

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