Background: African-American (AA) women with breast cancer have a less favorable prognosis, likely due to differences in tumor biology. This is not only driven by the higher rate of triple negative/basal tumors in patients with AA ancestry, as worse outcome has also been seen in patients with luminal tumors. The Neoadjuvant BReast Cancer Symphony Trial (NBRST, NCT01479101) was a prospective trial that has shown an association of MammaPrint/BluePrint (MP/BP) with a rate of pathologic Complete Response (pCR) of 2% in Luminal A with 95% Distant Metastasis Free Interval at 3 years. Here, we determine the MP/BP risk distribution, response to therapy, and outcome in African American (AA) and Caucasian (Cau) patients. Methods: NBRST enrolled 1,072 breast cancer patients (pts) in the US (June 2011 and December 2014), median follow-up 34.9 months. The current unplanned analysis compared clinicopathological characteristics, molecular risk assignment and outcome with neoadjuvant chemotherapy (NACT) in AA and Cau pts. Molecular subtyping groups were assessed by MP/BP as follows: Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2 and Basal types. Results: Out of 1,072 pts, 157 (15%) were AA, and 780 (73%) were Cau. AA patients were younger at diagnosis (52 vs 54 yrs; p = 0.016), had a higher likelihood of having higher grade (gr 3, 65% vs 53%; p = 0.005), ER-negative (45% vs 33%; p = 0.005) and lymph node positive tumors (71% vs 51; p < 0.001). MP/BP classified more AA patients as Basal type, 45% compared to 33% of Cau patients (p = 0.004). Fewer AA patients were classified as Luminal A (15%) compared to Cau pts (33%; p = 0.004). In multivariate analysis race was a significant factor for higher pCR rates to NACT in AA compared to Cau pts, together with PR, HER2, T-stage and Grade (HR = 1.679, 95% CI = (1.057, 2.67), p = 0.028). The pCR rate to NACT in patients with Basal tumors was 38% and similar in AA and Cau patients. In patients with hormone receptor positive and HER2 negative tumors, patients classified by MP/BP as Luminal A had lower pCR (2%) compared to non-luminal A (13%) (p = 0.0015). MP low risk patients had higher 3 yr DMFS (97%) than MP high risk patients (86%; p = 0.010). DMFS for AA MP Low Risk patients was 100%. Conclusions: In this study, MP was able to identify patients with hormone receptor positive tumors with low sensitivity to chemotherapy and good outcome, irrespective of race, suggesting that this test can be helpful to characterize the tumor’s biology and select patients who will not benefit from chemotherapy independently of their ancestry. Clinical trial information: NCT01479101