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#Grand Rounds

Is Multigene Testing in All Women with Breast Cancer Cost-Effective? And is it a Good Idea?

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BACKGROUND AND PURPOSE:

  • More pathogenic mutation carriers could be identified with genetic testing panels that incorporate more genes
    • The cost-effectiveness of this approach has not been addressed
  • Sun et al. (JAMA Oncol., 2019) assessed cost-effectiveness of multigene testing of all patients with breast cancer compared to the current practice of determining eligibility for genetic testing based on family history or clinical criteria

METHODS:

  • Cost-effectiveness microsimulation modeling study
  • Setting
    • United Kingdom (UK) and US populations
  • Participants and data sources
    • Data from population-based breast cancer cohorts recruited to 4 large research studies
  • Strategies tested
    • Strategy A
      • BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with breast cancer
    • Strategy B
      • BRCA1/BRCA2 testing only based on family history or clinical criteria
  • Study design
    • Women identified as carriers could opt of prophylactic surgical procedures (e.g., mastectomy and/or risk-reducing salpingo-oophorectomy (RRSO)
    • Relatives of mutation carriers underwent cascade testing and those who were carriers could potentially undergo
      • Magnetic resonance imaging or mammography screening
      • Chemoprevention
      • Risk-reducing mastectomy for breast cancer risk and RRSO for ovarian cancer risk
    • Costs (2016 prices): Included genetic testing, pretest and posttest genetic counseling, breast cancer and ovarian cancer treatment, excess CHD after premenopausal RRSO, and productivity loss
  • Primary outcome: Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained

RESULTS:

  • Data from 11,836 patients were analyzed
  • Multi-gene panel with early detection of carriers and uptake of prophylactic measures could lead to
    • UK
      • 1,142 fewer breast cancer cases
      • 959 fewer ovarian cancer cases
      • 633 fewer deaths due to breast or ovarian cancer
    • US
      • 5,478 fewer breast cancer cases
      • 4,255 fewer ovarian cancer cases
      • 2,406 fewer deaths due to breast or ovarian cancer
  • Compared with current BRCA testing based on clinical criteria or family history alone, BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost
    • Payer perspective: £10,464/QALY
    • Societal perspective: £7216/QALY
  • In the United States, BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost
    • Payer perspective: $65,661/QALY
    • Societal perspective: $61,618/QALY
  • Results well below UK and US cost-effectiveness thresholds
  • 8 excess deaths due to heart disease would have occurred in the UK and 35 in the United States annually

CONCLUSION:

  • The authors claim that the results of this study found multi-gene testing for all women with breast cancer to be “extremely cost-effective” vs current guidelines where genetic screening is offered based on the clinical scenario and family history
    • The authors of the study suggest that these results support a change in guidelines for genetic testing of women with breast cancer  
  • However, Robson and Domchek, in their viewpoint piece published alongside this study, question the true clinical utility of multigene testing 
    • Existing guidelines do identify patients with known pathogenic variants that have clear therapeutic implications
    • Larger testing panels will mean finding pathogenic variants that may not clear and well-studied treatment options  
    • Benefits of multigene testing to family members are not well established
      • May lead to harms from overtreatment
    • Treatment options, especially those that may not be necessary can lead to additional costs that were not adequately factored in to this study

Learn More – Primary Sources:

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

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Related ObG Topics:

Single Gene vs Multigene Panel Testing for Cancer Predisposition: Are Guidelines Too Restrictive?
BRCA1 & BRCA2 Mutations: What Are the Risks for Developing Breast and Ovarian Cancer?
Should We Be Testing Beyond BRCA1/2 in Women of Ashkenazi Jewish Heritage with Breast Cancer?
USPSTF Guidelines for Primary Care Clinicians: BRCA-Related Cancer Risk Assessment

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