Immune checkpoint inhibitors (ICI) have been incorporated into standard treatment regimens for patients with early and advanced triple-negative breast cancer (TNBC). Unlike in TNBC, the first studies to test the efficacy of ICI in patients with metastatic estrogen receptor-positive (ER+) disease showed limited efficacy, probably reflecting the lower immunogenicity of these tumors compared with TNBC. However, building on the knowledge that primary tumors are often less immunosuppressed than pretreated malignancies, and that combining ICI with cytotoxic agents may elicit antitumor immune responses, early studies have explored this strategy in the preoperative setting. A pathological complete response (pCR) rate of 16% was observed among 43 patients with Luminal B-like breast cancer treated with neoadjuvant chemotherapy (NACT), followed by nivolumab in combination with endocrine therapy (ET) in the GIADA trial.8 In the I-SPY2 trial, the addition of pembrolizumab to NACT increased estimated pCR rates from 13% to 30% in 40 patients with ER+/human epidermal growth factor receptor 2 (HER2)-negative (HER2) MammaPrint-high breast cancer, suggesting that at least a subgroup of patients with ER+ disease could derive benefit from the addition of immune checkpoint blockade.