Background: Adjuvant chemotherapy for early breast cancer is associated with a small risk of developing MDS and AML. The aim of this study is to determine the risk of developing AML or MDS after modern adjuvant chemotherapy in older breast cancer patients and to further define the risk of individual chemotherapy regimens.
Methods: Patients diagnosed with stage I-III breast cancer from 2003 to 2009 were identified in the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Development of AML or MDS, chemotherapy use, and comorbidities were identified using ICD-9 and HCPCS codes. A single inpatient or 2 outpatient codes 30 days apart were required for identification of AML or MDS. Analyses included descriptive statistics, Kaplan-Meier method for 5-year AML/MDS rates and Cox proportional hazards models to estimate the hazard of AML and MDS after adjusting for clinically relevant covariates.
Results: 68,702 patients were included, of them 166 (0.24%) developed AML and 385 (0.56%) developed MDS. The median time from breast cancer diagnosis to AML or MDS was 924 and 943 days respectively. The 5-year AML rates were 0.23% for the no chemotherapy group, 0.53% for anthracycline (A)-based regimens, 0.48% for anthracycline and taxane (AT)-based regimens, 0.39% for other (O) regimens and 0.09% for those who received docetaxel and cyclophosphamide (TC). 5-year MDS estimates were 0.62%, 1.07%, 0.72%, 1.08 and 0.38% respectively. In the multivariable model using no chemotherapy as the reference category, A (HR 3.03; 95%CI 1.75-5.24) and AT (HR 3.06; 95%CI 1.70-5.52) were the chemotherapy regimens associated with the highest risk for developing AML, followed by O (HR 2.05; 95%CI, 1.13-3.69). No significant increase in risk was observed in patients who received TC (HR 0.91; 95%CI 0.26-4.60). Similar results were observed when evaluating risk of MDS among patients treated with A (HR 2.25; 95%CI, 1.50-3.37), AT (HR 1.67; 95%CI 1.06-2.65), O (HR 2.30; 95%CI 1.61-3.29) and TC (HR 1.22; 95%CI 0.60-2.66).
Conclusion: In this large cohort of patients we observed a small but significant increase in risk for AML and MDS with adjuvant chemotherapy. The highest risk was associated with A and AT-based chemotherapy. TC was the only regimen that was not significantly associated with an increased risk. Because of relative recent adoption of TC, longer follow-up is needed to better estimate the risk of MDS and AML in this group of patients.
Citation Format: Aron S Rosenstock, Sharon H Giordano, Jiangong Niu, Hui Zhao, Antonio C Wolff, Thomas A Buchholz, Mariana Chavez-MacGregor. AML and MDS after adjuvant chemotherapy: A population based study among older breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-04.