Effectiveness of pegylated liposomal doxorubicin (Caelyx®) monotherapy in patients with metastatic HER2-low breast cancer: a monocentric retrospective study

Context Breast cancer (BC) is the most common cancer worldwide, and anthracyclines remain a key component of systemic therapy despite expanding treatment options. A refined HER2 classification has recently emerged, distinguishing HER2-negative (IHC score 0), HER2-low, and HER2-positive tumors. While HER2-low status predicts response to trastuzumab–deruxtecan, its biological significance remains uncertain. Anthracyclines have shown superior activity in HER2-positive BC, potentially through ERBB2/TOP2A co-amplification, but their effectiveness in HER2-low tumors has not been evaluated. This study assessed whether HER2-low status predicts anthracycline benefit in metastatic BC. Methods We conducted a single-center retrospective study including 114 patients with HER2-negative or HER2-low metastatic BC treated with pegylated liposomal doxorubicin (PLD) between 2013 and 2021. The primary endpoint was real-world progression-free survival (rwPFS). Results Median rwPFS was 2.6 months (95% CI, 2.1–3.2) in HER2-low disease and 3.1 months (95% CI, 2.3–3.8) in HER2 score 0 disease, with no statistically significant difference. In multivariable analysis, HER2-low status was not independently associated with rwPFS. Conclusion PLD demonstrated modest efficacy in metastatic BC lacking HER2 overexpression, with comparable outcomes in HER2-low and HER2-negative subgroups. These findings suggest that HER2-low status does not predict anthracycline benefit and support the view that HER2-low is unlikely to represent a distinct therapeutic subtype. Further research is needed to refine treatment selection in this heterogeneous population.