Efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy in breast cancer: a systematic review and meta-analysis with focus on triple-negative subtype and immune-related adverse events

To systematically evaluate the efficacy and safety of chemotherapy combined with PD-1/PD-L1 inhibitors in breast cancer, thereby informing clinical decision-making. A comprehensive search was conducted in PubMed, Cochrane Library, Embase, CNKI, Wanfang, and VIP databases from inception to August 2025 for randomized controlled trials (RCTs) comparing chemotherapy plus PD-1/PD-L1 inhibitors versus chemotherapy alone in breast cancer. Two reviewers independently screened studies, extracted data, and assessed quality using the Cochrane risk of bias tool. Meta-analysis was performed using RevMan 5.3. Primary outcomes were progression-free survival (PFS) and pathological complete response (pCR). Secondary outcomes included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). Nineteen RCTs involving 6,546 patients were included. The combination therapy significantly improved pCR(OR = 1.83, 95% CI 1.28–2.62, P < 0.001), PFS (HR = 0.81, 95% CI 0.76–0.87, P < 0.00001), and ORR (OR = 0.62, 95% CI 0.39–0.96, P = 0.03) compared to chemotherapy alone. OS was significantly improved in the combination group (HR = 0.87, 95% CI 0.81–0.94, P = 0.0007). No significant difference was found in CBR (P = 0.07). Safety analysis revealed a higher incidence of grade ≥ 2 AEs (OR = 1.13, P < 0.001), primarily non-hematological toxicities, and a significant increase in immune-related adverse events (irAEs), which were predominantly grade 1–2. Subgroup analyses indicated greater benefit in triple-negative breast cancer (TNBC) and PD-L1-positive populations, with optimal PFS observed with taxane-based regimens. The addition of PD-1/PD-L1 inhibitors to chemotherapy significantly enhances efficacy in breast cancer, particularly for patients with PD-L1-positive TNBC, at the cost of an increased but manageable risk of low-grade irAEs. Clinical implementation should be guided by biomarker testing and proactive toxicity monitoring.