Study: All Women With Breast Cancer, Regardless of Family History, Should Undergo Genetic Testing

Laura Joszt

While current guidelines recommend that only women with breast cancer who have a family history (FH) or who meet clinical criteria undergo genetic testing, a new cost-effectiveness analysis suggests that genetic testing should be expanded to all women with breast cancer.

The research, published in JAMA Oncology,1 estimated incremental lifetime effects, costs, and cost-effectiveness of multigene testing by comparing strategy A, in which all women with breast cancer underwent BRCA1/BRCA2/PALB2 testing, with strategy B, in which only women who had a FH or met clinical criteria underwent testing.

According to the authors, a strategy for genetic testing that relies on FH or clinical criteria requires patients and their physicians to be aware and understand the importance of FH, communication among family, and timely referrals to get genetic testing. In addition, limited awareness among providers and patients, restrictions on genetic counseling services, and other factors have led to the underuse of genetic testing services.

“Current restricting of testing to FH- or clinical criteria–based selection misses important opportunities to prevent [breast cancer] and [ovarian cancer] in unaffected individuals,” the authors wrote.

They analyzed data on 11,836 women in 4 large breast cancer clinical trials and research cohorts in the United States, United Kingdom, and Australia. Moving to strategy A would result in 1142 fewer breast cancer cases, 959 fewer ovarian cancer cases, and 663 fewer deaths due to breast cancer or ovarian cancer in the United Kingdom. In the United States, there would be 5478 fewer breast cancer cases, 4255 fewer ovarian cancer cases, and 2406 fewer deaths due to either cancer.

In the United Kingdom, testing all patients with breast cancer would cost £10,464 per quality-adjusted life-year (QALY) gained from a payer perspective or £7216/QALY from a societal perspective. In the United States, strategy A would cost $65,661/QALY from payer perspective or $61,618/QALY from a societal perspective compared with the current strategy of genetic testing based on clinical criteria or FH.

“Our analysis suggests that an unselected testing strategy is extremely cost-effective for UK and US health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the authors concluded.

The study follows a guideline update by the United States Preventive Services Task Force (USPSTF) that had added the clinical criteria of women who have survived and completed treatment for breast, ovarian, tubal, or peritoneal cancer or have a family history, which expanded the pool of women eligible. It indicated that women with ancestry associated with a higher susceptibility to BRCA1/2 mutations should be assessed. Women of Ashkenazi Jewish descent have a 1 in 40 risk (10 times higher than the general population) of inheriting a BRCA mutation.

In an editorial in August that accompanied the USPSTF update, authors argued that the recommendation leaves some issues unresolved, but they did cite concerns over the growing use of multigene panel testing (MGPT), which can create challenges, such as detecting variants of uncertain significance.2

“The clinical utility of the indiscriminate use of MGPT has not been established, and genetics education of primary care clinicians has not kept pace with either the influx of new information or the changes in the genetic testing marketplace,” the authors had written. “While there may be value in expanding BRCA testing, particularly in the Ashkenazi Jewish population, this does not automatically mean that this expansion should be conducted using MGPT.”

1. Sun L, Brentnall A, Patel S, et al. A cost-effectiveness analysis of multigene testing for all patients with breast cancer [published online October 3, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.3323
2. Domchek S, Robson M. Broadening criteria for BRCA1/2 evaluation; placing the USPSTF recommendation in context [published online August 20, 2019]. JAMA. doi: 10.1001/jama.2019.9688.
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