To identify genomic alterations and signalling pathways associated with treatment failure in patients with metastatic HER2-enriched (HER2-E) hormone receptor-positive (HR+) breast cancer (BC): DNA and RNA of >400 HR+ samples (including 140 HER2-E) from 4 metastatic cohorts will be extracted and analyzed for genomic alterations. Massive parallel sequencing (MPS; MiSeq Illumina platform) will be used to detect somatic mutations on a panel of 60 oncogenes and tumour suppressor genes, covering most frequently mutated exons including PIK3CA, TP53, CDH1, GATA3 and ESR1 as well as tumour mutational burden. The nCounter Breast Cancer 360 Panel (Nanostring Technologies) will be used to determine the expression of 752 genes across 23 key BC pathways and processes. Intrinsic subtypes and biologically relevant gene signatures will be determined using R software. Subsequent phenotypic characterization will take place.