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Among 930 TCGA patients, those of African ancestry were nearly four times as likely to have basal-like cancer, had more TP53 and fewer PIK3CA mutations and relapsed sooner; about 44% of the subtype difference was explained by inherited variants.
Tumour and matched normal data for 930 TCGA breast cancer patients (154 black patients of African ancestry, 776 white of European ancestry) were compared. Black patients had a worse breast cancer-free interval (HR 1.67), higher odds of basal-like (OR 3.80) and HER2-enriched (OR 2.22) subtypes, more TP53 and fewer PIK3CA mutations. Most molecular differences disappeared after adjusting for intrinsic subtype, leaving 16 methylation probes, 4 copy-number segments, 1 protein and 142 genes differentially expressed. Heritability of basal versus non-basal subtype from germline genotypes was 0.436; the ER-negative polygenic risk score was much higher in black patients.
The excess of triple-negative disease in women of African ancestry is substantially genetic in origin rather than only social, which supports ancestry-aware risk models and trial enrolment.
Shares PAM50 / intrinsic subtypes, PIK3CA / PI3K-alpha, TP53, Breast cancer (all types).
Shares PIK3CA / PI3K-alpha, TP53, Triple-negative breast cancer (TNBC).
Shares TP53, Breast cancer (all types), Triple-negative breast cancer (TNBC).
Shares JAMA Oncology, Breast cancer (all types), Triple-negative breast cancer (TNBC).
Shares PAM50 / intrinsic subtypes, Breast cancer (all types).
Shares PAM50 / intrinsic subtypes, Triple-negative breast cancer (TNBC).
Shares PAM50 / intrinsic subtypes, PIK3CA / PI3K-alpha, TP53, Triple-negative breast cancer (TNBC).