Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease that remains challenging to target with traditional therapies and to predict risk. We provide a comprehensive characterization of 238 stage II-III TNBC tumors with paired RNA and DNA sequencing data from the CALGB 40603 (Alliance) clinical trial, along with 448 stage II-III TNBC tumors with paired RNA and DNA data from three additional datasets. We identify DNA mutations associated with RNA-based subtypes, specific TP53 missense mutations compatible with potential neoantigen activity, and a consistently highly altered copy number landscape. We train exploratory multi-modal elastic net models of TNBC patient overall survival to determine the added impact of DNA-based features to RNA and clinical features. We find that mutations and copy number show little to no prognostic value, while RNA expression features, including signatures of T cell and B cell activity, along with stage, improve stratification of TNBC survival risk.
Authors
- Katherine A. Hoadley (ORCID: https://orcid.org/0000-0002-1216-477X)
- George Somlo
- Brooke Felsheim (ORCID: https://orcid.org/0000-0001-8421-8290)
- Michele C. Hayward (ORCID: https://orcid.org/0000-0003-0921-1368)
- William M. Sikov (ORCID: https://orcid.org/0000-0001-5451-6449)
- Lisa A. Carey (ORCID: https://orcid.org/0000-0003-2388-4649)
- Adam D. Pfefferle (ORCID: https://orcid.org/0000-0002-4924-1767)
- Charles M. Perou (ORCID: https://orcid.org/0000-0001-9827-2247)
- Aranzazu Fernández-Martínez (ORCID: https://orcid.org/0000-0002-2311-4356)
- Naim U. Rashid (ORCID: https://orcid.org/0000-0002-7274-8259)
- Sara M. Tolaney (ORCID: https://orcid.org/0000-0002-5940-8671)
- Cheng Fan (ORCID: https://orcid.org/0000-0002-3471-6221)
Institutions
- University of North Carolina at Chapel Hill (US)
- University of North Carolina Health Care (US)
- Brown University (US)
- City of Hope (US)
- Women & Infants Hospital of Rhode Island (US)
- Dana-Farber/Harvard Cancer Center (US)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-03-08
- DOI
- https://doi.org/10.1038/s41523-025-00740-z
- Citations
- 5
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 4.68
Funders
- Breast Cancer Research Foundation
- Susan G. Komen
- National Cancer Institute