biostudies-literatureFelsheim BMBreast Cancer Research Foundation (BCRF)U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Susan G. Komen (Susan G. Komen Breast Cancer Foundation)NCI NIH HHSNIGMS NIH HHS24https://www.ebi.ac.uk/biostudies/studies/S-EPMC11890565biostudies-literatureUnknown11(1)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 finNPJ breast cancerPrognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets.PMC11890565U10CA180882T32 GM135123R01-CA14876U10 CA180882P50 CA058223UG1 CA233180BCRF-23-127U24 CA196171SAC-160074P50-CA058223U10 CA180821U10 CA180888U10CA180821U24CA176171Sikov WMTolaney SMFelsheim BMHoadley KACarey LAPfefferle ADSomlo GPerou CMFernandez-Martinez AFan CHayward MCRashid NUfalsePrognostic 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 fin2025-01-01T00:00:00Z2025 Mar2026-06-01T20:12:19.749Z2025-04-06T08:35:06.193ZS-EPMC118905654005751110.1038/s41523-025-00740-z