All Women with Breast Cancer Should Undergo Multigene Testing, Study Suggests

Multigene testing for all woman diagnosed with breast cancer can be “extremely cost-effective.”

Multigene testing for all woman diagnosed with breast cancer can be “extremely cost-effective” compared to testing based on family history or clinical factors in both the United States and the United Kingdom health care systems, according to authors of a new analysis published in JAMA Oncology. 

“These findings support changing current policy to expand genetic testing to all women with breast cancer,” concluded senior author Ranjit Manchanda, MD, PhD, of the Barts Cancer Institute, Queen Mary University of London in England, and coauthors. 

The microsimulation modeling study compared multigene BRCA1/BRCA2/PALB2 testing of all unselected patients with BRCA1/BRCA2testing based on family history or clinical factors. Data for 11,836 patients from 4 large studies were used to assess cost effectiveness (incremental cost per quality-adjusted life-year [QALY] gained) for each testing strategy under US and UK health system conditions. 

“Affected BRCA/PALB2 [mutation] carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO),” the study authors reported. “Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention, or risk-reducing mastectomy for BC risk and RRSO for ovarian cancer (OC) risk.”

BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC would cost between $61,618 and $65,661 per QALY in the United States compared with current BRCA testing based on family history and clinical factors, the model suggested.

“I find these findings topical and believe that US policy-makers should take them into consideration in their future recommendations for genetic counseling and genetic testing for BRCA-related cancer,” said Natalia R. Kunst, a PhD candidate at the University of Oslo and a research fellow at the Yale University School of Medicine.

“The US Preventive Services Task Force (USPSTF) currently recommends against genetic counseling and testing for women without a personal or family history associated with BRCA1or BRCA2 gene mutations,” Kunst noted. 

The microsimulation study “convincingly demonstrates that genetic testing provided to all breast cancer patients represents a cost-effective strategy when compared with genetic testing provided only to patients fulfilling family history and clinical criteria,” Kunst said. 

“This is a thoroughly performed simulation study with access to extensive and unique data from four clinical research studies conducted in three countries,” she said. “The authors developed a complex microsimulation model that accounted for patients’ heterogeneity and performed a probabilistic sensitivity analysis and a number of one-way sensitivity analyses to propagate and examine uncertainty in their analysis.”

A next step could be a “value of information (VOI)” analysis to quantify the value of additional research on multigene testing for patients with breast cancer, Kunst suggested. That could help decision makers decide whether to implement an immediate policy change based on the currently available evidence or to await additional research, she explained.

Kunst and colleagues recently published a VOI analysis involving 21-gene assay for breast cancer management, she noted. 

“We found that the benefits and cost-effectiveness of 21-gene assay in women with intermediate and high risk of recurrence are well established but uncertainty regarding the cost-effectiveness of 21-gene assay in low-risk women persists,” Kunst said.


The microsimulation study was funded by the US National Cancer Institute.


Sun L, Brentnall A, Patel S, et al. A Cost Effectiveness Analysis of Multigene Testing for All Patients with Breast Cancer. JAMA Oncol. Published online October 3, 2019.