Molecular Characterization and Classification of HER2-Positive Breast Cancer Inform Tailored Therapeutic Strategies.

Autor:	Li YW; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Dai LJ; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Wu XR; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Zhao S; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Xu YZ; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Jin X; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Xiao Y; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Wang Y; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Lin CJ; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Zhou YF; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Fu T; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Yang WT; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China., Li M; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China., Lv H; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China., Chen S; School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom., Grigoriadis A; School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom., Jiang YZ; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Ma D; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Shao ZM; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2024 Nov 04; Vol. 84 (21), pp. 3669-3683.
DOI:	10.1158/0008-5472.CAN-23-4066
Abstrakt:	HER2-positive breast cancer is an aggressive subtype that accounts for 15% to 20% of all breast cancers. Recent studies have suggested that HER2-positive breast cancer is a group of heterogeneous diseases with different sensitivities to standard treatment regimens. Revealing the molecular heterogeneity of HER2-positive breast cancer could potentially enable more precise treatment strategies. In this study, we performed multiomics profiling on a HER2-positive breast cancer cohort and identified four transcriptome-based subtypes. The classical HER2 (HER2-CLA) subtype comprised 28.3% of the samples and displayed high ERBB2 activation and significant benefit from anti-HER2 therapy. The immunomodulatory (HER2-IM) subtype (20%) featured an immune-activated microenvironment, potentially suitable for de-escalated treatment and immunotherapy. The luminal-like (HER2-LUM) subtype (30.6%) possessed similar molecular features of hormone receptor-positive HER2-negative breast cancer, suggesting endocrine therapy and CDK4/6 inhibitors as a potential therapeutic strategy. Lastly, the basal/mesenchymal-like (HER2-BM) subtype (21.1%) had a poor response to current dual HER2-targeted therapy and could potentially benefit from tyrosine kinase inhibitors. The molecular characteristics and clinical features of the subtypes were further explored across multiple cohorts, and the feasibility of the proposed treatment strategies was validated in patient-derived organoid and patient-derived tumor fragment models. This study elucidates the molecular heterogeneity of HER2-positive breast cancer and paves the way for a more tailored treatment. Significance: Illumination of the inherent heterogeneity within HER2-positive breast cancers through the delineation of distinct molecular subtypes lays the groundwork for developing more personalized treatment strategies based on specific patient characteristics. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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