There was ethical review and approval for all protocols used in this study from the respective centers involved and all subjects gave written informed consent to participate. A training set was developed using 171 breast samples, comprised of 16 “normal” breast tissue samples from reduction mammoplasties or grossly uninvolved breast tissue and 155 primary invasive breast cancers. These samples were collected from 2005–2009 under IRB approved protocols at the University of Utah and the University of North Carolina at Chapel Hill. Clinical-pathological information associated with the samples is based on the College of American Pathology (CAP) and American Joint Committee on Cancer (AJCC) standards at the time of collection (Additional file 1 ). Subtype classification and single and meta-gene (proliferation) scores were predicted on an independent test set of 814 samples from the GEICAM/9906 clinical trial, a randomized Phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel [22 (link)]. Patients that were hormone receptor positive (ER and/or PR positive by IHC) were given adjuvant tamoxifen. The hormone receptor status for these samples was evaluated at a single site (Department of Pathology, Hospital General Universitario de Alicante) using immunohistochemistry (IHC) for progesterone receptor (PR) (clone PgR636, DAKO, Glostrup, Denmark) and estrogen receptor (ER) (clone 1D5, DAKO, Glostrup, Denmark) (Additional file 2 ). The scores for the proportion of dyed cells and intensity were summed to obtain a total Allred Score [23 ]. Measurement of HER2 expression was performed by Herceptest™ (DAKO, Glostrup, Denmark) and samples with scores of 2+ by IHC were confirmed by CISH, following the ASCO/CAP guidelines [24 (link)]. The clinical data for the training set and GEICAM/9906 test set are summarized in Table 1 .
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