Predicted chemotherapy benefit for breast cancer patients with germline pathogenic variants in cancer susceptibility genes

• Type of Material: Article
• Authors: Allison W. Kurian, Stanford University; Kevin Ward, Emory University; Paul Abrahamse, University of Michigan School of Public Health; Ann S. Hamilton, University of Southern California; Steven J. Katz, University of Michigan School of Public Health
• Language: English
• Date: 2021-01-01
• Publisher: Oxford University Press
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/JNCICS/PKAA083
• Title of Journal or Parent Work: JNCI Cancer Spectrum
• Volume: 5
• Issue: 1
• Grant/Funding Information: Research reported in this publication was supported by the National Cancer Institute (NCI) of the National Institutes of Health under award number R01 CA225697 to Stanford University. The collection of cancer incidence data in Georgia was supported by contract HHSN261201800003I, Task Order HHSN26100001 from the NCI and cooperative agreement 5NU58DP006352-03–00 from the Centers for Disease Control and Prevention (CDC). The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; CDC’s National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the NCI’s Surveillance, Epidemiology and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute, Cancer Registry of Greater California. The ideas and opinions expressed herein are those of the author(s) and do not necessarily reflect the opinions of the State of California, Department of Public Health, the NCI, and the CDC or their contractors and subcontractors.
• Keywords: Genetic Testing; SEER Program; Age Factors; Humans; Aged; Ataxia Telangiectasia Mutated Proteins; Breast Neoplasms; Female; Multivariate Analysis; Checkpoint Kinase 2; Adult; Germ-Line Mutation; Genetic Predisposition to Disease; Georgia; Fanconi Anemia Complementation Group N Protein; Colorectal Neoplasms, Hereditary Nonpolyposis; Neoplasm Recurrence, Local; Genes, BRCA2; Middle Aged; California; Genes, BRCA1
• Research Categories: Health Sciences, Radiology; Health Sciences, Oncology; Biology, Genetics

Abstract

Breast cancer patients increasingly undergo genetic testing. To examine chemotherapy indications for germline pathogenic variant (PV) carriers, we linked results of germline testing to Georgia and California Surveillance, Epidemiology, and End Results registry records, including 21-gene recurrence score (RS) results, for breast cancer patients diagnosed in 2013-2017. All statistical tests were 2-sided. Patients (N 37 349) had RS results of whom 714 had BRCA1, BRCA2, CHEK2, ATM, PALB2, or Lynch syndrome (MLH1, MSH2, MSH6, PMS2) PVs. For women aged 50 years or older at breast cancer diagnosis, RS often exceeded the chemotherapy benefit threshold (_26) with BRCA1 (71.7% vs 14.4% with none; P <.001), PALB2 (37.1%; P .001), and BRCA2 (44.3%; P < .001) PVs. Results were similar for women diagnosed at younger than 50 years of age. PVs in BRCA1, but not BRCA2, PALB2, ATM, CHEK2, or Lynch syndrome genes, were associated with elevated RS on multivariable analysis (P < .001). Results may inform RS testing decisions in breast cancer patients with PVs.