Prognostic and predictive impact of gene expression in node‐positive early breast cancer patients receiving dose‐dense versus standard‐dose adjuvant chemotherapy
| Title: | Prognostic and predictive impact of gene expression in node‐positive early breast cancer patients receiving dose‐dense versus standard‐dose adjuvant chemotherapy |
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| Authors: | Mattea Reinisch, Simona Bruzas, Oleg Gluz, Beyhan Ataseven, Peter Schmid, Javier Cortés, Jens‐Uwe Blohmer, Satyendra Shenoy, Mark H. Dyson, Christine Dittmer‐Grabowski, Ouafaa Chiari, Hakima Harrach, Daniel Gebauer, Alexander Traut, Sherko Kuemmel |
| Source: | Molecular Oncology, Vol 17, Iss 6, Pp 1060-1075 (2023) |
| Publisher Information: | Wiley, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | adjuvant chemotherapy, dose‐dense chemotherapy, early breast cancer, gene signature, lymph node‐positive, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | The utility of multigene expression assays in advanced (≥ 4 positive lymph nodes) early breast cancer (EBC) is limited. We conducted exploratory transcriptomic analysis of 758 genes (Breast Cancer 360 panel, nCounter® platform; NanoString) in primary tumor samples collected during a phase 3 trial comparing adjuvant taxane‐containing dose‐dense chemotherapy (ddCTX) versus standard‐dosed chemotherapy (stCTX) in resected EBC with ≥ 4 positive lymph nodes. Prognostic and predictive associations with disease‐free survival (DFS) and overall survival (OS) were evaluated by Cox regression with false discovery rate (FDR) adjustment. Data were available from tumor samples of 141/226 patients (median follow‐up: 14 years). Several genes/signatures, including immune markers, showed prognostic relevance in unadjusted analyses. Of these, two remained significant after multiplicity adjustment: a positive effect on DFS of programmed cell death 1 ligand‐2 (PD‐L2) in the ddCTX arm (univariate HR: 0.53, FDR‐adjusted P = 0.036) and a negative effect on OS of HER2‐enriched (HER2‐E) signature in the stCTX arm (univariate HR: 5.40, FDR‐adjusted P = 0.036). Predictive analyses showed greater DFS benefit of ddCTX in tumors with high antigen processing machinery (APM) expression (multivariate interaction P = 0.024). Multigene expression assays have a prognostic and predictive potential in advanced EBC, and further investigation is warranted in order to identify candidates for de‐escalated treatment. In addition, intrinsic subtype and immune gene expression have predictive potential. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.13435 |
| Access URL: | https://doaj.org/article/7a55781affb14d02a3ca8331da1192e4 |
| Accession Number: | edsdoj.7a55781affb14d02a3ca8331da1192e4 |
| Database: | Directory of Open Access Journals |
| ISSN: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13435 |
| Published in: | Molecular Oncology |
| Language: | English |