Multigene testing replacing BRCA tests for breast cancer risk, researcher says

May 10, 2018, Stanford University Medical Center
Three-dimensional culture of human breast cancer cells, with DNA stained blue and a protein in the cell surface membrane stained green. Image created in 2014 by Tom Misteli, Ph.D., and Karen Meaburn, Ph.D. at the NIH IRP.

The use of genetic tests aimed at detecting the presence of mutations in the BRCA1 and BRCA2 genes in women with breast cancer is rapidly declining in favor of tests that can detect multiple cancer-associated mutations, according to researchers at the Stanford University School of Medicine and five other U.S. medical centers.

Some researchers had wondered whether multigene testing, which may identify genetic mutations of uncertain clinical significance, would lead more women to consider prophylactic mastectomies—a surgery in which both breasts are removed to prevent future cancers—out of an abundance of caution. However, the current study did not show an increase in mastectomies associated with testing more genes.

The shift reflects a growing acknowledgement by clinicians that multigene panel tests can yield more clinically useful information for patients and their unaffected relatives, the researchers said.

Overall, multigene panels were about twice as likely as the tests for BRCA1 and BRCA2 to identify disease-associated genetic variants, the study found. However, multigene testing was more likely than the BRCA-only testing to be delayed until after surgery to remove the tumor. This time lag may limit a patient's treatment options, the researchers said.

'Becoming the norm'

"In general, multigene panel tests yield more clinically useful results and are rapidly becoming the norm," said Allison Kurian, MD, associate professor of medicine and of health research and policy at Stanford. "Newly diagnosed women should ask their doctors whether they may be appropriate candidates for . 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."

A paper describing the research will be published May 10 in JAMA Oncology. Kurian is the lead author. Steven Katz, MD, MPH, professor of medicine and of health management and policy at the University of Michigan, is the senior author.

Multigene panel tests are more likely than BRCA-only tests to yield information about both a patient and her family members, who may be unwitting carriers of disease-associated mutations. "This is very important because it offers the opportunity for genetically targeted, primary cancer prevention in unaffected relatives," Kurian said. "Some prior research has shown that this 'cascade testing' of unaffected relatives is cost-effective, and there are currently several initiatives underway to improve upon the delivery and success rates of cascade testing."

The researchers surveyed over 5,000 women who had been diagnosed with stage-0 to stage-2 breast cancer between 2013 and 2015. They asked the women if they'd had genetic testing, and, if so, who ordered it, when it was performed and what type of tests they underwent. A novel feature of this study was that genetic results came directly from the testing laboratories and were linked to population-based cancer registry data. This data linkage provided substantially greater depth and accuracy of genetic information than in previous studies.

They found that only about one-quarter of the women had received any genetic testing. This number stayed relatively constant throughout the two-year period. However, of those who were tested, the proportion who received multigene panel testing increased steadily over time, from about 26 percent of those tested in early 2013 to about 66 percent in mid-2015. Conversely, the proportion of women who received BRCA-only testing during the same time period decreased from about 74 percent to about 34 percent.

Multigene panel testing was about twice as likely as BRCA-only testing to identify disease-associated mutations. But it was also more likely to reveal mutations of uncertain clinical significance, particularly in racial or ethnic minorities. This disparity is likely due to the fact that most genes were sequenced first in white patients, and the causative effect of variations in other minorities is not clear. This finding emphasizes the need for research in diverse populations to clarify genetic uncertainty and reduce racial disparities in the clarity of genetic results, the researchers say.

Timing of tests varied

The timing of the tests also varied, the study found. Although the majority of the women tested got their results prior to surgery to remove the tumor, many did not. About 33 percent of women receiving multigene panel testing were tested after surgery, versus about 20 percent of women receiving BRCA-only testing—perhaps due to a recognition by clinicians that interpreting the results of a multigene panel can be complex and requires the expertise of genetic counselors, who are not always rapidly available.

"Furthermore, 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," said Katz.

"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."

Explore further: Some breast cancer patients are missing out on genetic counseling

Related Stories

Some breast cancer patients are missing out on genetic counseling

March 12, 2018
As new genes are linked to breast cancer occurring in families and as genetic testing becomes more important in directing treatment for newly diagnosed patients, a substantial number of those at the highest risk are not getting ...

Breast cancer genes a real risk for men, too

April 26, 2018
(HealthDay)—Few American men are screened for gene mutations that can greatly increase their risk of breast and other types of cancers, a new study reveals.

Mutations common in pancreatic CA, history of other cancers

February 7, 2018
(HealthDay)—A substantial proportion of individuals with pancreatic cancer and a history of other hereditary breast and ovarian cancer (HBOC)- or Lynch syndrome (LS)-related cancers have mutations in a prostate cancer susceptibility ...

Gender disparity observed in cancer genetic testing in the U.S.

May 3, 2018
(HealthDay)—Specific demographic groups have lower cancer genetic testing, including unaffected men compared with unaffected women, according to a research letter published online April 26 in JAMA Oncology.

Findings suggest a gap between need, availability of genetic counseling

February 7, 2017
Physicians often fail to recommend genetic testing for breast cancer patients at high risk for mutations associated with ovarian and other cancers, according to a large study by researchers at the Stanford University School ...

Physicians' misunderstanding of genetic test results may hamper mastectomy decisions

April 12, 2017
A recent survey of over 2,000 women newly diagnosed with breast cancer found that half of those who undergo bilateral mastectomy after genetic testing don't actually have mutations known to confer increased risk of additional ...

Recommended for you

Daily low-dose aspirin may be weapon against ovarian cancer

July 20, 2018
(HealthDay)— One low-dose aspirin a day could help women avoid ovarian cancer or boost their survival should it develop, two new studies suggest.

Discovery of kidney cancer driver could lead to new treatment strategy

July 19, 2018
University of North Carolina Lineberger Comprehensive Cancer Center scientists have uncovered a potential therapeutic target for kidney cancers that have a common genetic change. Scientists have known this genetic change ...

High fruit and vegetable consumption may reduce risk of breast cancer, especially aggressive tumors

July 19, 2018
Women who eat a high amount of fruits and vegetables each day may have a lower risk of breast cancer, especially of aggressive tumors, than those who eat fewer fruits and vegetables, according to a new study led by researchers ...

Sunscreen reduces melanoma risk by 40 per cent in young people

July 19, 2018
A world-first study led by University of Sydney has found that Australians aged 18-40 years who were regular users of sunscreen in childhood reduced their risk of developing melanoma by 40 percent, compared to those who rarely ...

Analysis of prostate tumors reveals clues to cancer's aggressiveness

July 19, 2018
Using genetic sequencing, scientists have revealed the complete DNA makeup of more than 100 aggressive prostate tumors, pinpointing important genetic errors these deadly tumors have in common. The study lays the foundation ...

Complementary medicine for cancer can decrease survival

July 19, 2018
People who received complementary therapy for curable cancers were more likely to refuse at least one component of their conventional cancer treatment, and were more likely to die as a result, according to researchers from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.