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Use of SNPs Boosts Accuracy of Breast Cancer Risk Assessment


By Marilynn Larkin

NEW YORK (Reuters Health) – A panel of 18 SNPs (SN18) “substantially improves” breast cancer risk prediction and identification of women who may benefit most from preventive therapy or additional screening, researchers say.

“The main use of tests for common variants, or SNPs, is to better define the likelihood of someone developing a particular problem,” Dr. Gareth Evans of St. Mary’s Hospital in Manchester, UK, told Reuters Health. “Breast cancer is an area which has seen a great deal of research to identify these SNPs.”

“Overall, SNPs now account for more of the inherited component of breast cancer than all ‘high-risk’ genes such as BRCA1 and BRCA2 combined,” he said in an email. “Because very many cases and controls have been used to derive ‘odds ratios’ for these SNPs, the estimates are very accurate and robust.”

“Even when multiplied together to form a polygenic risk score, the accuracy still remains extremely high,” he added. “Thus, if the SNP18 score estimated a 2-fold relative risk, this is exactly what we have seen in prospective follow-up.”

To assess the value of adding SNP18 to mammographic density and classic risks as assessed by the Tyrer-Cruzick risk model, Dr. Evans and colleagues enrolled a subcohort of 9,363 women (mean age, 59) without a previous diagnosis of breast cancer. All were participants in the prospective cohort of the PROCAS (Predicting Risk of Cancer at Screening) multicenter study in Greater Manchester, England.

Enrollment took place from October 2009 through June 2015, with follow-up through January 5, 2017.

As reported online January 18 in JAMA Oncology, 466 women had breast cancer (271 prevalent; 195 incident). SNP18 was similarly predictive when unadjusted or adjusted for mammographic density and classic risk factors, with the observed risks being very close to expected.

A combined risk assessment identified 18% of the subcohort to be at 5% or greater 10-year risk, compared to 30% of all cancers; 35% of interval-detected cancers; and 42% of stage 2 or higher cancers.

By contrast, 33% of the subcohort had less than a 2% risk, accounting for 18%, 17%, and 15% of the total, interval, and stage 2 or higher breast cancers, respectively.

Women in the highest-risk (at least 8%) group were more than four times as likely to develop cancer, as measured by both the prevalent mammogram and prospectively, as the low-risk (<2%) group.

In addition, 14% of the cancers occurred in the highest-risk group, which made up only 6% of the population; the moderate/high-risk group was five times more likely to develop a high-stage cancer than the low-risk group.

The authors conclude that SNP18 “added substantial information” to classic risk assessment and that “a combined risk is likely to aid risk-stratified screening and prevention strategies.”

Dr. Evans said, “SNP18 only needs to be performed once and is not a test for ‘cancer’ at that time point. As such, women wanting to know their future breast cancer risk only need have the test at their first assessment.”

“For women in the general population with little or no family history of breast cancer,” he continued, “SNP18 offers a far more meaningful test than a test for BRCA1 and BRCA2 and a host of other high- or moderate-risk cancer genes.”

“Less than 2% of the population will get a meaningful result for a breast cancer gene,” Dr. Evans noted. “Tests for a SNP panel are very much cheaper than for extended gene panels.”

“We are about to launch a SNP18 test for non-BRCA families and the general population that is likely to cost no more than £120 (US$158),” he concluded.

Dr. Dana Zakalik, corporate medical director, Cancer Genetics at Beaumont Health in Royal Oak, Michigan, told Reuters Health by email, “This is a well-executed study with significant findings.”

Nevertheless, she noted, “This trial needs further validation, and needs to be correlated with patient outcomes.”

“With proper education and infrastructure support,” she added, “this approach should be able to be offered to many patients.”

“Clinicians need to recognize advancements in breast cancer risk assessment, as well as the different options for personalized screening and prevention,” Dr. Zakalik said. “It is important to identify women (at increased risk) and offer them risk-adapted screening and prevention.”


JAMA Oncol 2018.

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