Tumor genomics in patients younger than 40 years of age with metastatic breast cancer
Unique disease characteristics of younger patients warrants investigation of tumor genomics in young-onset metastatic breast cancer (MBC). Targeted DNA sequencing was completed for tumors of MBC patients diagnosed between 2009-2020. Multivariable logistic regression tested associations between single nucleotide variants (SNVs) and copy number variants and age at MBC diagnosis. Multivariable Cox regression estimated hazard ratios for overall survival (OS) by somatic alterations. Among 2,357 MBC patients, tumors of those ≤40 years at diagnosis (vs. >55) were more likely to harbor amplifications in ERBB2 and MYC (p < 0.01) and mutations in TP53 (odds ratio [OR] = 1.83, p < 0.001), and less likely to harbor mutations in CDH1 and PIK3CA (p < 0.001). OS was shorter among younger recurrent MBC patients [median: 2.8 (≤ 40) vs. 3.6 years ( > 55), p = 0.04], with SNVs in TP53 and PTEN associated with shorter OS. Distinct tumor genomics of young-onset MBC patients suggest differences in tumor biology that should guide investigation of targetable pathways.
Authors
- Maggie Loucks
- Gregory John Kirkner (ORCID: https://orcid.org/0009-0005-0386-5223)
- Melissa E. Hughes (ORCID: https://orcid.org/0000-0001-6190-9101)
- Barbara LeStage
- Janet Files
- Ayesha Mohammed-Abreu
- Anne-Marie Feeney
- Yvonne Li (ORCID: https://orcid.org/0000-0002-1741-1995)
- Ananya Bhargavi Kodali
- Brittany L. Bychkovksy
- Nancy U. Lin
- R. B. Sousa
- L. Sholl
- S. Strauss
- D. Dillon
- B. E. Johnson
- K. D. Brantley
- Ann H. Partridge
- Charlotte Tannenbaum
- Sara M. Tolaney
- Andrew D. Cherniack
- Ana C. Garrido-Castro
- Tari King
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Emory University (US)
- Yale Cancer Center (US)
- D’Or Institute for Research and Education (BR)
- Dana-Farber Cancer Institute (US)
- Dana-Farber/Harvard Cancer Center (US)
- Hospital Universitário de Brasília (BR)
- Cancer Genetics (United States) (US)
- Dana-Farber Brigham Cancer Center (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-02-26
- DOI
- https://doi.org/10.1038/s41698-026-01333-0
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Breast Cancer Research Foundation
- Pfizer
- Dana-Farber Cancer Institute
- Dana-Farber/Harvard Cancer Center
- National Comprehensive Cancer Network
- National Cancer Institute