Long-term risk of second primary malignancies and symptomatic heart failure after pegylated liposomal doxorubicin versus conventional anthracycline-based chemotherapy in early-stage breast cancer survivors: a single-center experience

Abstract Background Anthracycline-based chemotherapy is a crucial treatment for early-stage breast cancer but be associated with second primary malignancy (SPM) and heart failure (HF). Pegylated liposomal doxorubicin (PLD) has been used as an alternative to conventional non-pegylated anthracyclines; however, long-term data regarding SPM and symptomatic HF after PLD-based treatment remain limited. This study evaluated the long-term risks of SPM and symptomatic HF and compared survival outcomes between PLD-based and conventional anthracycline-based regimens. Methods We retrospectively analyzed 1,372 patients with early-stage breast cancer treated at Ditmanson Medical Foundation Chia-Yi Christian Hospital from January 2010 to December 2021. Patients were categorized into a reference group without neoadjuvant/adjuvant chemotherapy, a PLD group, and a conventional anthracycline group (non-PLD) treated with doxorubicin or epirubicin. The risks of SPM and symptomatic HF were analyzed using Cox regression and competing-risk models. Cardinality matching at a 1:4 ratio was used to compare disease-free survival (DFS) and overall survival (OS) between the PLD and conventional anthracycline groups. Results Overall, the 10-year cumulative incidences of SPM in the reference and non-PLD groups were 9.5% and 9.8%, respectively. The 10-year cumulative incidence of hematologic malignancy after conventional anthracycline exposure was 0.5%. Risk factors for SPM included age ≥ 40 years and stage II disease. Thirty-nine patients developed symptomatic HF, with risk factors including BMI ≥ 24 and stage III disease. After 1:4 cardinality matching, 51 patients in the PLD group and 204 patients in the non-PLD group were matched. No significant differences in DFS or OS were observed between the PLD and non-PLD groups. Conclusions In this single-center cohort of early-stage breast cancer survivors, neither PLD-based nor conventional anthracycline-based chemotherapy was associated with a significantly increased risk of SPM or symptomatic HF compared with patients who did not receive chemotherapy. PLD-based regimens showed comparable survival outcomes to conventional anthracycline-based regimens after cardinality matching analysis. These findings support PLD as a potential alternative anthracycline formulation, particularly for patients with cardiac risk factors; however, the low number of events and the small PLD cohort preclude conclusions of equivalence or definitive cardiac safety.