Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial
- Author(s)
- Rediti, M; Venet, D; Joaquin Garcia, A; Maetens, M; Vincent, D; Majjaj, S; El-Abed, S; Di Cosimo, S; Ueno, T; Izquierdo, M; Piccart, M; Pusztai, L; Loi, S; Salgado, R; Viale, G; Rothé, F; Sotiriou, C;
- Details
- Publication Year 2024-11-29,Volume 15,Issue #1,Page 10402
- Journal Title
- Nature Communications
- Publication Type
- Research article
- Abstract
- In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial (NCT00490139), we identify and characterize five molecular subtypes associated with the risk of distant recurrence: immune-enriched, proliferative/metabolic-enriched, mesenchymal/stroma-enriched, luminal, and ERBB2-dependent. Additionally, we validate the biological profiles of the subtypes and explore their prognostic/predictive value in external cohorts, namely the NeoALTTO trial (NCT00553358), SCAN-B (NCT02306096), I-SPY2 (NCT01042379), METABRIC and TCGA. Immune-enriched tumors present better survival outcomes, in contrast to mesenchymal/stroma-enriched and proliferative/metabolic-enriched tumors, while luminal and ERBB2-dependent tumors are characterized by low and high rates of pathological complete response, respectively. Of note, these molecular subtypes provide the rationale for treatment approaches leveraging the heterogeneous biology of HER2-positive breast cancer.
- Publisher
- Springer Nature
- Keywords
- Humans; *Breast Neoplasms/genetics/drug therapy/pathology/metabolism; Female; *Receptor, ErbB-2/metabolism/genetics; *Trastuzumab/therapeutic use; Prognosis; Biomarkers, Tumor/metabolism/genetics; Gene Expression Profiling; Tumor Microenvironment/genetics; Gene Expression Regulation, Neoplastic; Middle Aged; Antineoplastic Agents, Immunological/therapeutic use; Neoplasm Recurrence, Local/genetics
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s41467-024-54621-3
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-024-54621-3- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-19 05:48:10
Last Modified: 2024-12-19 05:48:41