A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer

Abstract

IMPORTANCE Moving to multigene testing for all women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, the cost-effectiveness of this approach remains unaddressed. OBJECTIVE To estimate incremental lifetime effects, costs, and cost-effectiveness of multigene testing of all patients with BC compared with the current practice of genetic testing (BRCA) based on family history (FH) or clinical criteria. DESIGN, SETTING, AND PARTICIPANTS This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations. Data were obtained from 11 836 patients in population-based BC cohorts (regardless of FH) recruited to 4 large research studies. Data were collected and analyzed from January 1, 2018, through June 8, 2019. The time horizon is lifetime. Payer and societal perspectives are presented. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty. INTERVENTIONS In strategy A, all women with BC underwent BRCA1/BRCA2/PALB2 testing. In strategy B, only women with BC fulfilling FH or clinical criteria underwent BRCA testing. Affected BRCA/PALB2 carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO). 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. MAIN OUTCOMES AND MEASURES Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with standard £30 000/QALY and $100 000/QALY UK and US thresholds, respectively. Incidence of OC, BC, excess deaths due to heart disease, and the overall population effects were estimated. RESULTS BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost £10 464/QALY

Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States

“…28 The costs for mammography, MRI, and prophylactic procedures were derived from published sources. 13 , 27 Cancer costs were assessed for the first year of treatment, for continuing treatment in subsequent years, and as palliative therapy for the last year of life. 27 We assumed that the transition to death from any 1-year or after cancer health state incurred palliative treatment costs.…”

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

“…As per national guidelines, in some subgroups (e.g., Ashkenazi Jewish heritage), all women with breast cancer are recommended to undergo genetic testing. 13,29 Of note, a recent paper considered the cost-benefit ratio of multigene panel testing for all breast cancer patients 31 and while the modeling results might be overly optimistic, these types of efforts are crucial in generating data to inform testing practices.…”

The contemporary landscape of genetic testing and breast cancer: Emerging issues

“…One approach is diagnosis-based testing, for example, test all patients with breast cancer. 7,14,15 The American Society of Breast Surgeons (ASBS), for example, endorses testing for all patients with breast cancer that includes at least BRCA1, BRCA2, and PALB2. 14 A second approach is population offering, that is, offering testing broadly, regardless of whether or not an individual has a personal or family history of cancer.…”

“…A follow-up analysis found the population screening approach to be more cost-effective than the family history-based approach over a range of scenarios. 15 A frequently cited concern with population testing is the potential for excess psychologic distress, although a prospective study conducted in Israel reported high satisfaction and no excess psychologic harm with a streamlined BRCA screening approach in unaffected Ashkenazi Jewish individuals. 19 With broadened testing criteria, resources will need to be directed toward access to cancer genetics services to ensure safe and effective delivery of care.…”