Abstract PS2-04-05: Long-term outcomes and toxicities of doxorubicin-cyclophosphamide chemotherapy in breast cancer: a McGill University Health Centre experience, 100-month interim analysis

Abstract Background: Doxorubicin-cyclophosphamide (AC) has remained a cornerstone of breast cancer therapy for over four decades.1,2 Despite its widespread use in clinical trials, long-term data and toxicity data remain limited in non-clinical trial patients. Chronic complications such as chemotherapy-induced cardiomyopathy (CIMP), defined by left ventricular dysfunction, and chemotherapy-induced leukemia carry important quality-of-life consequences.4-6 In this study, we assessed the efficacy and toxicity of AC chemotherapy in a real-world cohort of breast cancer patients with a median follow-up of 8.1 years. Methods: We conducted a descriptive analysis of a prospectively maintained institutional database, including breast cancer patients treated with AC chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) in the adjuvant or neoadjuvant setting at the McGill University Health Centre from 2016 to 2025, with a median follow-up time of 8.1 years. Primary outcomes included metastatic recurrence (rate and site), all-cause mortality, cardiotoxicity, and hematological malignancies. Subgroup analyses were performed based on age, stage, and tumor subtype. Statistical analyses included descriptive statistics for baseline characteristics, Fisher’s exact tests for categorical comparisons, Kaplan-Meier estimates for survival outcomes, and multivariable Cox proportional hazards models. All analyses were conducted using R (v4.5.1). Results: A total of 98 patients were included in the final analysis. All patients were women, with a mean age of 60.7 ± 12.0 years. Most were diagnosed with invasive ductal carcinoma (87.8%) and had stage II disease (56.1%). No patients were lost to follow-up, with a median follow-up duration of 97 months. Excluding those with de novo metastatic disease (7 patients), recurrence occurred in 13 of 91 patients (14.3%), with a median time to recurrence of 40.1 months. Metastatic rates were significantly higher in stage III compared to stage I-II disease (42.1% vs. 6.9%, p < 0.001). No significant difference in recurrence was observed across tumor subtypes (p = 0.919). The most common metastatic sites were bone (84.6%) and liver (76.9%). Overall mortality was 18.4%, significantly higher in advanced-stage (stage III-IV) patients compared to early-stage (stage I-II) disease (50.0% vs. 6.9%, p < 0.001). Triple-negative breast cancer had the highest subtype-specific mortality (29.4%). Five-year overall survival was 88.7%, with advanced stage at diagnosis emerging as the only statistically significant independent predictor of mortality (HR 8.96, 95% CI 3.19-25.18; p < 0.001). The cardiotoxicity rate was 1.0%, with one patient developing CIMP-defined heart failure (LVEF 10-15%) and requiring coronary care unit admission. No secondary hematologic malignancies were observed. Conclusion This eight-year, prospectively collected real-world dataset confirms outcomes reported in randomized clinical trials. The favourable long-term survival and low rates of metastasis, as well as an acceptable long-term safety profile, reinforce the use of doxorubicin-cyclophosphamide (AC) chemotherapy in high-risk patients. CIMP was an uncommon but important toxicity. Citation Format: E. Rohr, T. Alotaibi, F. Moria, N. Bouganim. Long-term outcomes and toxicities of doxorubicin-cyclophosphamide chemotherapy in breast cancer: a McGill University Health Centre experience, 100-month interim analysis [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 PS2-04-05.