Multigene Testing for All Breast Cancer Patients Cost-Effective for UK, US: Study

By Marilynn Larkin

October 14, 2019

NEW YORK (Reuters Health) - Expanding genetic testing to all women with breast cancer is "extremely" cost-effective for the US and UK and could prevent thousands of breast or ovarian cancers and deaths, researchers say.

"Current national and international guidelines recommend genetic-testing (for BRCA genes) in women with breast cancer who fulfill recognized/established clinical criteria which are based on a history of cancer in the patient and family," Dr. Ranjit Manchanda of Queen Mary University of London, UK, told Reuters Health.

But 50% of BRCA carriers don't meet these criteria, so this approach misses half the people at risk, he said via email.

"Additionally, only 20%-30% of patients eligible tend to get referred for and access BRCA testing," he noted. "Newer genes like PALB2 which cause breast cancer have been identified and can also be tested for."

In a microsimulation study, Dr. Manchanda and colleagues compared lifetime costs and effects of two genetic testing strategies in women with breast cancer in the UK and US. In strategy A, all women undergo BRCA1/BRCA2/PALB2 (multigene) testing. In strategy B (the current strategy), only women who fulfill current family history or clinical criteria undergo BRCA1/BRCA2 testing.

Affected BRCA/PALB2 carriers could have a contralateral preventive mastectomy and BRCA carriers could select risk-reducing salpingo-oophorectomy.

Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention or risk-reducing mastectomy for breast cancer risk; or risk-reducing mastectomy for ovarian cancer risk.

As reported online October 3 in JAMA Oncology, compared with the current strategy, universal multigene testing would be "well below" UK and US cost-effectiveness thresholds: £10,464/QALY (payer perspective) or £7216/QALY (societal perspective) annually in the UK and $65,661/QALY (payer perspective) or $61,618/QALY (societal perspective) in the U.S.

In probabilistic sensitivity analysis, unselected multigene testing remained cost-effective for 98% to 99% of UK and 64% to 68% of US health system simulations.

Further, one year's unselected multigene testing could prevent 2,101 cases of breast and ovarian cancer and 633 deaths in the UK, and 9,733 breast/ovarian cancer cases and 2,406 deaths in the US.

Dr. Manchanda said, "Testing everyone instead of being restricted by family history will identify many more mutation carriers and their family members who can benefit from precision prevention. A large proportion of these cancers are preventable in known unaffected mutation carriers."

"A similar approach has already been implemented for ovarian cancer over the last few years," he said, "and now we need to do it in breast cancer, too."

Clinical geneticist Dr. Jeffrey Weitzel, Director, Cancer Screening and Prevention Programs Network and Director, Cancer Genomics Education Program at City of Hope in Duarte, California, told Reuters Health by phone, "At our last National Comprehensive Cancer Network guideline committee meeting, it was decided that there wasn't adequate evidence to support applying genetic testing to all breast cancer patients."

"This paper is only saying we can afford to do it; there's no new medical data," he noted. "But the guideline is not about money; it's about quality and avoidance of harm, as well as doing good."

"Their model assumes that all at-risk relatives get tested," he added, "and there's published data that shows the highest uptake of cascade testing ever reported was 48%. Their model remained cost-effective after adjustment for a 70% uptake - but again, that doesn't mean quality/avoidance of harm."

"Even bona fide mutations in some of these genes lack evidence-based guidelines for care," he added. "Many physicians apply BRCA care (i.e., mastectomy) for moderate-risk genes, which is not risk-appropriate. We need to assure medical quality, not just cost-effectiveness, before we change guidelines and practice."

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SOURCE: http://bit.ly/2OCPPST

JAMA Oncol 2019.

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