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Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890565 | PMC |
| http://dx.doi.org/10.1038/s41523-025-00740-z | DOI Listing |
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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.
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Article Synopsis
- Early-stage triple-negative breast cancer (TNBC) has variability in its clinical and biological characteristics, with immune infiltration impacting prognosis, and there’s a need for better genomic tools for treatment decisions.
- This study analyzed genomic and clinical data across seven patient cohorts to evaluate the role of a B-cell/immunoglobulin signature (IGG) in predicting event-free survival (EFS) and overall survival (OS) in TNBC patients.
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CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer.
J Clin Oncol
April 2022
Program in Women's Oncology, Women and Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University, Providence, RI.
Purpose: CALGB 40603 (NCT00861705), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points.
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