BackgroundThis study aimed to evaluate the efficacy and safety of docetaxel plus capecitabine (TX) and docetaxel plus epirubicin (TE) in the treatment of human epidermal growth factor 2 (HER2)-negative breast cancer.MethodsRelevant studies assessing the efficacy and safety of TX versus TE were systematically searched from PubMed, Cochrane Library, Embase, and Web of Science databases until February 6, 2025. Progression-free survival (PFS), and clinical response, including the overall response rate (ORR), disease control rate (DCR), and grade 3/4 adverse events were compared.ResultsFour articles with moderate methodological quality were included. The pooled results revealed no significant differences in PFS (hazard ratio [HR] (95% confidence interval CI) = 0.86 (0.70, 1.05), P = 0.14), ORR (risk ratio [RR] (95%CI) = 1.02 (0.92, 1.14), P = 0.71), or DCR (RR (95%CI) = 1.02 (0.92, 1.14), P = 0.71) between the TX and TE groups. For grade 3/4 adverse events, only the combined results for neutropenia (RR (95%CI), 0.71 (0.52, 0.95); P = 0.02) and hand-foot syndrome (RR (95%CI) = 14.36 (3.45, 59.84); P = 0.0003) demonstrated significant differences between the two groups. No significant differences were observed in other adverse events, including febrile neutropenia, anemia, thrombocytopenia, nail/hair toxicity, hepatic toxicity, diarrhea, nausea, vomiting, infection, asthenia, and neuropathy.ConclusionIn patients with HER2-negative breast cancer, TX and TE have comparable survival benefits and efficacy. However, TX exhibits a reduced incidence of neutropenia, but a higher likelihood of hand-foot syndrome than that observed in TE.