Secondary Myeloid Neoplasms in Older Women with Breast Cancer after Radiotherapy: A Population-Based Study

BACKGROUND: Chemotherapy and combined chemo-radiotherapy are well-documented risk factors for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), collectively referred to in this setting as therapy-related myeloid neoplasms (t-MN). While single-modality radiotherapy post-lumpectomy has been shown to reduce local recurrence among breast cancer patients, data regarding the impact on development of t-MN are limited and inconsistent. 

METHODS: We conducted a retrospective cohort study of elderly female breast cancer patients (aged 67-94 years at diagnosis) who were diagnosed with in situ or stage 1-3 breast cancer between 1/1/2004 and 12/31/2011 using the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER)–Medicare linked database. Eligibility criteria included 1) enrollment in Medicare Parts A and B continuously through death or end of study (12/31/2013); 2) underwent surgery for breast cancer within 9 months of diagnosis; and 3) were not diagnosed with other neoplasms prior to breast cancer diagnosis. Delivery of radiation therapy was ascertained using the Healthcare Common Procedural Coding System codes. In order to be considered a recipient of radiotherapy, the patient had to receive radiotherapy within 9 months of diagnosis and had any treatment delivery code for brachytherapy or ≥ 4 treatment delivery codes for external bream radiotherapy. Competing-risk analysis was used to assess the risk of developing t-MN in radiotherapy-treated patients compared to those treated with surgery alone. Patients were censored at the time of receiving chemotherapy or at development of another malignancy (aside of t-MN) during follow-up. Competing-risk analysis was used to assess the risk of developing secondary MN women who received radiation therapy compared to those who did not.  These models included adjustment for breast cancer diagnosis age and year, number of comorbidities, anemia, functional status prior to breast cancer diagnosis and breast cancer stage.

RESULTS: A total of 63,543 patients were included in the study. Median follow-up for all participants was 48 months. A total of 32,809 patients (51.6%) received radiotherapy post-surgery while 30,734 patients (48.4%) were not treated with radiotherapy post-surgery. Patients who received radiotherapy had significantly better overall survival than those who did not (median overall survival [OS] 107 vs. 89 months, p<0.001). During follow-up, a total of 167 patients were diagnosed with MDS or AML (89 cases among those who received radiotherapy and 78 among those who did not receive radiotherapy). The median time to develop MDS/AML was 24 months. In the unadjusted model, there was no significantly increased risk of subsequent AML/MDS among breast cancer patients who received single-modality radiotherapy compared to those who underwent surgery alone (hazard ratio [HR] = 1.11, 95% confidence interval [CI]: 0.82-1.51, p=0.49). Similarly, no significant difference in subsequent MDS/AML according to receipt of radiotherapy was observed in the adjusted analysis (HR = 1.16, 95% CI: 0.84-1.59, p=0.36).    

CONCLUSIONS: Older patients with early breast cancer who were treated with single-modality radiotherapy post-surgery did not have a higher risk of subsequent MDS/AML compared to patients who did not receive radiotherapy, and the overall rate of MN was low. While additional studies with a longer duration of follow-up are warranted, these results suggest that the single-modality radiotherapy administered in the contemporary management of early breast cancer is not a risk factor for t-MN in this population.