The therapeutic response of ER+/HER2− breast cancers differs according to the molecular Basal or Luminal subtype

• Published in: NPJ breast cancer Vol. 6; no. 1; p. 8
• Main Authors: Bertucci, François, Finetti, Pascal, Goncalves, Anthony, Birnbaum, Daniel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-03-2020; Nature Publishing Group; Nature
• Subjects: 631/67/1059/2326; 631/67/1347; Biomedical and Life Sciences; Biomedicine; Breast cancer; Brief Communication; Cancer; Cancer Research; Cancer therapies; Cell Biology; Chemotherapy; Endocrine therapy; Gene expression; Genomics; Human Genetics; Life Sciences; Lymphatic system; Medical research; Oncology; Tumors; Cancer therapeutic resistance; Breast cancer
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/s41523-020-0151-5

The genomics-based molecular classifications aim at identifying more homogeneous classes than immunohistochemistry, associated with a more uniform clinical outcome. We conducted an in silico analysis on a meta-dataset including gene expression data from 5342 clinically defined ER+/HER2− breast cancers (BC) and DNA copy number/mutational and proteomic data. We show that the Basal (16%) versus Luminal (74%) subtypes as defined using the 80-gene signature differ in terms of response/vulnerability to systemic therapies of BC. The Basal subtype is associated with better chemosensitivity, lesser benefit from adjuvant hormone therapy, and likely better sensitivity to PARP inhibitors, platinum salts and immune therapy, and other targeted therapies under development such as FGFR inhibitors. The Luminal subtype displays potential better sensitivity to CDK4/6 inhibitors and vulnerability to targeted therapies such as PIK3CA, AR and Bcl-2 inhibitors. Expression profiles are very different, showing an intermediate position of the ER+/HER2− Basal subtype between the ER+/HER2− Luminal and ER− Basal subtypes, and let suggest a different cell-of-origin. Our data suggest that the ER+/HER2− Basal and Luminal subtypes should not be assimilated and treated as a homogeneous group.