Abstract PS1-04-30: Breast cancer chemotherapy nearly doubles the risk of treatment-related AML and MDS: A systematic review and meta-analysis

Abstract Introduction: Chemotherapy continues to be a pillar of treatment for breast cancer (BC), and while it improves survival and reduces recurrence, there are significant side effects to acknowledge. One of the most serious long-term complications is the development of myeloid neoplasms post cytotoxic therapy (MN-pCT) (previously referred to as therapy-related myelodysplastic syndromes or acute myeloid leukemia). Individuals that developMN-pCTs have significant morbidity and reduction of overall life expectancy, despite improved breast cancer outcomes. The risk of developing t-AML/MDS in breast cancer patients who undergo chemotherapy compared to those who have not had chemotherapy has not been previously reported. Methods: To address this gap, we conducted a systematic review and meta-analysis to quantify the risk of MN-pCT among breast cancer patients treated with chemotherapy compared to those who did not receive chemotherapy. PubMed, Embase, and Cochrane databases were searched in March 2025. The search strategy included three search strings: breast cancer, leukemia or myelodysplastic syndrome or hematologic malignancy, and chemotherapy. Included articles were experimental or observational studies. Full texts were independently reviewed by two reviewers, with discrepancies resolved via consensus. The primary outcome was the pooled odds ratio (OR) for the development ofMN-pCT following chemotherapy exposure in BC patients compared to those who did not receive chemotherapy. Random-effects meta-analysis was used to calculate pooled ORs and 95% confidence intervals (CIs). Publication bias was assessed using visual inspection of the funnel plot and Egger’s test for small-study effects. Heterogeneity was assessed with the I2 statistic, and meta-regression explored the impact of study-level factors such as anthracycline use, radiation, follow-up duration, publication year, age, and sample size. Results: Nineteen studies from 1985 to 2023 met inclusion criteria and included a total of 1,215,260BC patients (527,761 chemotherapy; 687,499 no chemotherapy). The studies consisted of2 randomized controlled trials, 1 case control study, and 16 retrospective cohort studies. The median follow-up time was 5.8 years. The pooled incidence of MN-pCT was 0.31%(chemotherapy) and 0.23% (no-chemotherapy). Chemotherapy was associated with an early two-fold increase in risk of AML/MDS (pooled OR 1.91 (95% CI: 1.41-2.58), p 0.001), with substantial heterogeneity (I2 = 82.9%). The estimated between-study variance(τ2) was 0.1810 (SE = 0.1167). Meta-regression showed that the proportion of patients receiving anthracyclines explained over half of the between-study heterogeneity (R2 =56.3%) but was not a statistically significant predictor of risk (p = 0.21). Notably, non-anthracycline regimens were also associated with a significant increase in MN-pCT risk. No significant associations were found for publication year, sample size, follow-up duration, age, or radiation exposure. Conclusion: We present the first meta-analysis that directly compares the risk of MN-pCT in patients with breast cancer who received cytotoxic chemotherapy versus those who did not receive chemotherapy. This risk was not confined to a specific regimen and is likely multifactorial in nature. Our results highlight the importance of risk-benefit discussions when pursuing chemotherapy, especially taking into consideration co-morbidities, life expectancy, and breast cancer risk profile. Additionally, future studies are needed to optimize surveillance strategies and develop and validate biomarkers to identify patients at risk of MN-pCTs after chemotherapy exposure. Citation Format: S. A. Roberts, A. M. Kagerer, N. J. Sareen, T. Haque, P. Razavi. Breast cancer chemotherapy nearly doubles the risk of treatment-related AML and MDS: A systematic review and meta-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 PS1-04-30.