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Purpose: Estrogen receptor-low (ER-low) breast cancer (BC) present clinicopathological features and disease behavior resembling triple-negative breast cancer, but have been frequently excluded from pivotal trials designed for the latter. Since neoadjuvant pembrolizumab plus chemotherapy (P + CT) is the new standard of care for stage II-III triple-negative breast cancer (TNBC), we aimed to access the effectiveness of this therapy for ER-low tumors., Methods: We evaluated patients with ER-low BC included in the Neo-Real/ GBECAM-0123 study, a real-world data study evaluating patients treated with neoadjuvant P + CT since July 2020 across ten cancer centers. The objective of this study was to evaluate the effectiveness of neoadjuvant P + CT through pathologic complete response (pCR)., Results: Twenty patients were included in this analysis. Median age was 40 years (range 28-64). Most patients had grade 3 tumors (n = 18, 90%), with a median Ki67 index of 75% (range 30-95%), and 70% had stage II tumors. All the twenty patients were submitted to surgery, with a pCR observed in 12 cases (pCR rate of 60%). Receiving less than 6 cycles of pembrolizumab was associated with a trend towards worse pCR rates (20% vs 73.3%)., Conclusions: The clinicopathological features and the response to neoadjuvant P + CT observed in this ER-low BC cohort are similar to that observed in TNBC. Patients with stage II-III ER-low/HER2- BC should be treated with neoadjuvant P + CT following the treatment standards for TNBC, and proper adherence to the regimen is relevant to improve effectiveness., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)