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Updated: Jul 15, 2025

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Molecular classification of hormone receptor-positive HER2-negative breast cancer
Xi Jin1, Yi-Fan Zhou1, Ding Ma1
1Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Abstract:
Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding precision treatment. We established a large-scale multi-omics cohort of 579 patients with HR+/HER2- breast cancer and identified the following four molecular subtypes: canonical luminal, immunogenic, proliferative and receptor tyrosine kinase (RTK)-driven. Tumors of these four subtypes showed distinct biological and clinical features, suggesting subtype-specific therapeutic strategies. The RTK-driven subtype was characterized by the activation of the RTK pathways and associated with poor outcomes. The immunogenic subtype had enriched immune cells and could benefit from immune checkpoint therapy. In addition, we developed convolutional neural network models to discriminate these subtypes based on digital pathology for potential clinical translation. The molecular classification provides insights into molecular heterogeneity and highlights the potential for precision treatment of HR+/HER2- breast cancer.
Insights
Researchers identified four molecular subtypes of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This classification aids in developing targeted therapies for endocrine therapy resistance and distant relapse.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common type.
- Endocrine therapy resistance and distant relapse are significant challenges in managing this subtype.
- Precise molecular classification is crucial for effective, personalized treatment strategies.
Purpose of the Study:
- To establish molecular subtypes within HR+/HER2- breast cancer.
- To investigate the distinct biological and clinical features of identified subtypes.
- To explore potential subtype-specific therapeutic approaches and diagnostic tools.
Main Methods:
- Establishment of a large-scale multi-omics cohort (579 patients).
- Identification and characterization of four molecular subtypes: canonical luminal, immunogenic, proliferative, and receptor tyrosine kinase (RTK)-driven.
- Development of convolutional neural network models for subtype classification using digital pathology.
Main Results:
- Four distinct molecular subtypes of HR+/HER2- breast cancer were identified.
- Subtypes exhibit unique biological and clinical characteristics, influencing treatment strategies.
- The RTK-driven subtype shows poor outcomes due to RTK pathway activation.
- The immunogenic subtype, with enriched immune cells, may benefit from immune checkpoint therapy.
Conclusions:
- Molecular classification of HR+/HER2- breast cancer reveals significant heterogeneity.
- Subtype-specific therapeutic strategies, including immune checkpoint therapy for the immunogenic subtype, are promising.
- Digital pathology-based classification using AI offers potential for clinical translation and precision treatment.
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