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.

Nature Genetics
|September 28, 2023
PubMed

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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