The PAMELA study is designed to test the hypothesis that the PAM50 HER2-E subtype is able to predict clinical response to neoadjuvant dual HER2 blockade with lapatinib and trastuzumab, with or without endocrine therapy, assessed by pathological complete response in the breast (pCRB) rate at the time of surgery, compared to traditional clinical HER2 classification. Furthermore, we posit that characterization of gene expression patterns may identify profiles of those who may be safely spared chemotherapy.