Breast cancer risk in female survivors of Hodgkin lymphoma after exposure to non-pegylated liposomal doxorubicin at young adult and adult age: the first real-life series from Southern Italy cancer centers

Studies in female Hodgkin lymphoma (HL) survivors have shown that doxorubicin hydrochloride exposure at young adult and adult (YA&A) age is associated with an increased risk of breast cancer (BC) regardless of chest-radiotherapy (c-RT). Although non-pegylated liposomal doxorubicin (NPLD)-based regimens have shown efficacy and safety in the treatment of lymphoma, the association between NPLD exposure and BC risk has not been examined in HL survivors. We assessed standardized incidence ratio (SIR) and absolute excess risk (AER) of BC in a cohort of 100 female ≥ 5-year HL survivors treated between 18 and 60 years of age with NPLD-based regimen in tertiary hospitals in southern Italy between 2009 and 2020. The median cumulative liposomal doxorubicin dose was 290 mg/m²; c-RT was administered to 20% of patients. After a median follow-up of 10 years (interquartile range, 8-11 years), no women had developed BC. Compared with the Italian general population, the SIR was 0.00 (95% confidence interval, 0.00-4.29); the standardized ratio was 86.5 per 100,000 person per year according to the AIRTUM (Associazione Italiana Registri Tumori) Working Group data for women aged between 18 and 60 years. In our series, the AER was - 8.87 per 10,000 person per year. Based on data derived from the pooled summary rate of literature, HL survivors treated with doxorubicin hydrochloride-including regimens at YA&A age had an incidence rate of BC of 1.6% at 10-year median follow-up. These data, if validated in largest datasets with longer follow-up, suggest that treatment with NPLD could be not associated with increased BC risk in HL survivors, unlike conventional doxorubicin. Our findings provide a rationale for evaluating NPLD-based frontline therapy in prospective studies of YA&A patients with newly diagnosed HL.