Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets
Abstract 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 CAL...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00740-z |
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| Summary: | Abstract 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. |
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| ISSN: | 2374-4677 |