Risk of febrile neutropenia in breast cancer chemotherapy despite the prophylactic use of pegfilgrastim: a retrospective analysis

BACKGROUND: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is used to prevent febrile neutropenia (FN) in breast cancer patients undergoing chemotherapy. However, a small subset of patients still develops FN. This study aimed to assess the real-world incidence of FN and identify potential risk factors in this specific population. METHODS: This retrospective study included breast cancer patients who received pegfilgrastim prophylaxis at Tokyo Medical University Hospital between February 2019 and December 2024. Inclusion required pegfilgrastim use at least once during chemotherapy. FN was defined as an absolute neutrophil count below 500/µL (or a predicted ANC below 1,000/µL) and an axillary temperature 37.5 °C or higher. Cases of FN and associated risk factors were analyzed using logistic regression models. RESULTS: This study included 378 patients (median age 53). Tumor subtypes were luminal (50.0%), HER2-positive (20.9%), and triple-negative (29.1%), with dose-dense regimens being the most common (55.8%). Of 2,784 total chemotherapy administrations, pegfilgrastim was used in 2,125 cycles (76.3%). The incidence of FN despite pegfilgrastim was 2.1% (8/378), with the highest rate observed in immune checkpoint inhibitor-containing regimens (9.1%, 2/22). Multivariate analysis identified a low baseline platelet count as a significant independent risk factor for combined FN and grade 3-4 neutropenia (OR: 0.98; 95% CI: 0.96-0.99; P = 0.02). CONCLUSION: Although pegfilgrastim is effective, FN still occurs in a small percentage of patients. A low baseline platelet count was associated with an increased risk of FN or severe neutropenia despite pegfilgrastim prophylaxis, though this finding requires confirmation in larger studies given the limited number of events.