Abstract Introduction: Granulocyte colony-stimulating factors (G-CSF) are essential supportive agents for patients receiving myelosuppressive chemotherapy, reducing febrile neutropenia (FN) and preserving chemotherapy dose intensity, especially in high-risk or dose-dense regimens.1-3 Guidelines recommend “primary prophylaxis” for patients at high risk for FN, while “secondary prophylaxis” is reserved for those with FN or borderline neutrophil counts during earlier cycles. While primary G-CSF benefits are well-documented, data on secondary prophylaxis, particularly in intermediate-risk regimens such as adjuvant doxorubicin-cyclophosphamide (AC) chemotherapy, are limited. Some studies suggest secondary G-CSF may reduce hospitalizations and improve treatment delivery, but robust, real-world, long-term safety data are lacking.5,6 A possible signal between G-CSF and secondary malignancies have been suggested.7 Accordingly, evaluation of the long-term safety of secondary prophylaxis is warranted. This study prospectively evaluated long-term safety and outcomes of secondary G-CSF prophylaxis in breast cancer patients treated with q3-weekly AC chemotherapy at the McGill University Health Centre. Methods: We conducted an interim analysis of a prospectively maintained database at the McGill University Health Centre (2016-2025). Ninety-eight patients who received q3-weekly AC chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) in the adjuvant or neoadjuvant setting, were included. Patients treated with dose-dense regimens or meeting criteria for primary G-CSF prophylaxis were excluded. Secondary G-CSF (filgrastim or pegfilgrastim) was administered at physician discretion to prevent dose reductions or delays. Key outcomes, including metastatic recurrence, mortality, overall survival, and follow-up time, were assessed using multivariable logistic regression and Cox proportional hazards models, adjusting for age, stage at diagnosis, and tumour subtype. All statistical analyses were conducted using R (v4.5.1). Results: Of 98 patients, 44 (45%) received secondary G-CSF. Fifty-eight percent of patients received G-CSF at cycle 2. Baseline characteristics were balanced between groups. No statistically significant difference in the incidence of new metastases was observed between the G-CSF and non-G-CSF groups (7.5% vs. 19.6%; adjusted OR 0.25, 95% CI 0.04-1.09; p = 0.09). No significant difference in all-cause mortality was observed (25% vs. 13%; adjusted OR 2.09, 95% CI 0.61-7.70; p = 0.25). Survival outcomes were comparable (5-year OS: 86.4% vs. 90.7%; adjusted HR 1.92, 95% CI 0.71-5.18; p = 0.20). Median follow-up among survivors was similar (96.8 vs. 94.6 months), with five-year follow-up exceeding 84% in both cohorts. No secondary hematologic malignancies occurred in either group. Conclusion: In this real-world cohort, secondary G-CSF prophylaxis during q3-weekly AC chemotherapy was not associated with significant differences in all-cause mortality between groups. No secondary hematological malignancies were observed. These results support the liberal use of secondary G-CSF in curative-intent regimens to prevent delays or reductions in dose intensity. Continued follow-up of this cohort is warranted to confirm long-term safety of liberal G-CSF use. Citation Format: E. Rohr, T. Alotaibi, F. Moria, N. Bouganim. Long-term safety in breast cancer patients receiving doxorubicin-cyclophosphamide chemotherapy with secondary G-CSF prophylaxis: A single-centre prospective study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-04-18.
Rohr et al. (Tue,) studied this question.