Background: Women with locally advanced breast cancer (LABC) are often treated with neo-adjuvant chemotherapy to reduce the size of the tumor prior to surgery, to enable breast conserving surgery and to observe the clinical effect of therapy in real time. Studies have shown that the 25–27% of individuals who have a pathologic complete response (pCR) to neoadjuvant therapy have a survival advantage of 80% in 5 years, which is double the expected survival of the remaining patients without pCR. If patients who are likely to show a pCR could be identified prior to initiation of therapy, it would enable more informed treatment decisions [von Minckwitz et al. JCO 2006]. Genomic assays, which are widely used to provide prognostic and predictive information in early breast cancer, have the potential to provide information on the likelihood of a patient with LABC responding to neo-adjuvant therapy [Glück et al. BRCRT 2013]. Methods: MINT is a prospective study designed to test the ability of molecular profiling, as well as traditional pathologic and clinical prognostic factors, to predict response to neo-adjuvant chemotherapy in patients with LABC. MammaPrint risk profile, BluePrint molecular subtyping profile, TargetPrint ER, PR and HER2 single gene readout, and TheraPrint Research Gene Panel will be analyzed on a fresh or formalin fixed paraffin embedded tumor specimen using the whole genome array. Patients will receive neo-adjuvant chemotherapy pre-specified in the protocol. Response will be measured by pCR and by centrally assessed RCB. The study will include women with histologically-proven invasive breast cancer T2 (≥3.5cm)-T4, N0M0 or T2-T4N1M0, adequate bone marrow reserves and normal renal and hepatic function who signed informed consent. Standard statistical tests such as the Pearson Chi-square test will be used to characterize and evaluate the relationship between chemoresponsiveness and gene expression patterns. A total of 226 eligible patients will be enrolled from 10 US institutions. 85 patients have been enrolled. Clinical trial information: NCT01501487.