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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| Format: | Article |
| Language: | English |
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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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| author | Brooke M. Felsheim Aranzazu Fernandez-Martinez Cheng Fan Adam D. Pfefferle Michele C. Hayward Katherine A. Hoadley Naim U. Rashid Sara M. Tolaney George Somlo Lisa A. Carey William M. Sikov Charles M. Perou |
| author_facet | Brooke M. Felsheim Aranzazu Fernandez-Martinez Cheng Fan Adam D. Pfefferle Michele C. Hayward Katherine A. Hoadley Naim U. Rashid Sara M. Tolaney George Somlo Lisa A. Carey William M. Sikov Charles M. Perou |
| author_sort | Brooke M. Felsheim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-06ec17c464ae4b028cb4819d65695c35 |
| institution | DOAJ |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-06ec17c464ae4b028cb4819d65695c352025-08-20T02:47:07ZengNature Portfolionpj Breast Cancer2374-46772025-03-0111111410.1038/s41523-025-00740-zPrognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasetsBrooke M. Felsheim0Aranzazu Fernandez-Martinez1Cheng Fan2Adam D. Pfefferle3Michele C. Hayward4Katherine A. Hoadley5Naim U. Rashid6Sara M. Tolaney7George Somlo8Lisa A. Carey9William M. Sikov10Charles M. Perou11Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillDana-Farber/Harvard Cancer CenterCity of Hope Comprehensive Cancer CenterLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillProgram in Women’s Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown UniversityLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillAbstract 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.https://doi.org/10.1038/s41523-025-00740-z |
| spellingShingle | Brooke M. Felsheim Aranzazu Fernandez-Martinez Cheng Fan Adam D. Pfefferle Michele C. Hayward Katherine A. Hoadley Naim U. Rashid Sara M. Tolaney George Somlo Lisa A. Carey William M. Sikov Charles M. Perou Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets npj Breast Cancer |
| title | Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets |
| title_full | Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets |
| title_fullStr | Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets |
| title_full_unstemmed | Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets |
| title_short | Prognostic and molecular multi-platform analysis of CALGB 40603 (Alliance) and public triple-negative breast cancer datasets |
| title_sort | prognostic and molecular multi platform analysis of calgb 40603 alliance and public triple negative breast cancer datasets |
| url | https://doi.org/10.1038/s41523-025-00740-z |
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