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The largest Chinese triple-negative cohort, 465 patients from Fudan, carried more PIK3CA mutations than American tumours and sorted into four subtypes, with the luminal androgen receptor type showing HER2 mutations and CDKN2A loss.
Clinical, genomic and transcriptomic data of 465 primary TNBCs were analysed. PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in the Chinese cohort than in The Cancer Genome Atlas. TNBCs were classified into four transcriptome-based subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed and mesenchymal-like, with putative therapeutic targets or biomarkers identified in each. The LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss.
The FUSCC cohort is the East Asian reference and the basis of the FUTURE subtype-guided umbrella trial; its LAR findings point to CDK4/6 and HER2-mutant strategies rather than PARP inhibitors for that subtype.
Shares Yi-Zhou Jiang, Zhi-Ming Shao, Zhongshan Hospital, Fudan University, Triple-negative breast cancer (TNBC).
Shares Androgen receptor, HER2, Triple-negative breast cancer (TNBC).
Shares CDKN2A, PIK3CA / PI3K-alpha, HER2.
Shares PIK3CA / PI3K-alpha, Triple-negative breast cancer (TNBC).
Shares Mutational signature, HER2.
Shares PIK3CA / PI3K-alpha, Triple-negative breast cancer (TNBC).