Comprehensive Breast Cancer Tissue Analysis

Hematoxylin and eosin (H&E) sections of 1,992 untreated primary invasive breast carcinomas described in the METABRIC study [15 (link)] were quality assessed. These sections are from female patients diagnosed between 1980 and 2005 from consecutive series from five contributing hospitals in the UK and Canada with clinical annotations and matched DNA and RNA profiling data. Of these, H&E samples from two hospitals were highly fragmented, leaving in total 1,026 cases from the remaining three hospitals, which were split into a test set of 510 samples (hospital 1 and 2; Cohort 1) and an independent validation set of 516 samples (hospital 3; Cohort 2) for retrospective analysis (Fig 1A; S1 Table). On average, three sections (top, middle, and bottom) were taken from the single frozen tumor aliquot included in the METABRIC study in order to represent the morphological profile of the tumor [15 (link),16 (link)]. Tumor sections were stained independently in different laboratories according to the hospital site. Whole-tumor section images, copy number profiled using Affymetrix SNP6, gene expression profiled using Illumina HT-12 array, and long-term follow-up data (median 68.3 mo) were obtained.