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

OBJECTIVE: To systematically evaluate the efficacy and safety of chemotherapy combined with PD-1/PD-L1 inhibitors in breast cancer, thereby informing clinical decision-making. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.