Through analysis of specimens from patients with primary triple-negative breast cancer (TNBC) enrolled in a neoadjuvant clinical trial assessing durvalumab with chemotherapy, we confirmed a novel 27-gene immuno-oncology (IO) signature that generates an IO score to predict the pathologic complete response (pCR) of primary TNBC to neoadjuvant immunotherapy with the PD-L1 blocker durvalumab with chemotherapy. Here, CD274 is linked to triple-negative breast carcinoma.