Introduction: Despite the availability of numerous novel targeted therapies in our daily clinical practice, chemotherapy remains a predominant treatment modality for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer, often extending beyond the third line. This study aimed to evaluate the efficacy and safety of third-line and subsequent chemotherapies, with the intent of contributing to the existing literature and addressing concerns regarding potential overtreatment in this patient population.
Materials and Methods: This retrospective, two-center study analyzed data from 35 chemotherapy protocols administered to 21 patients who received third, fourth, and fifth-line chemotherapy regimens. We evaluated the objective response rates (ORRs), progression-free survival (PFS), and rates of Grade 3–4 toxicities in this patient population.
Results: The ORR in this study was 14.2%. The PFS was 3.7 months, and 45.7% of patients experienced Grade 3 or 4 toxicities.
Discussion and Conclusion: Consistent with existing literature, our small, retrospective, two-center cohort demonstrated a low ORR, short PFS, and a high incidence of severe adverse events. These descriptive findings lack statistical power and cannot be generalized, but highlight the need for careful consideration of the risk–benefit ratio in heavily pre-treated patients. In this context, clinicians should thoughtfully evaluate best supportive care alongside chemotherapy, or consider alternative approaches such as hormonal therapy or novel targeted agents.