Therapy-Related Myeloid Neoplasms in Breast Cancer Patients: A Single-Institution Report of 150 Cases
Authors: Sevcikova Katarina , Zhuang Zuo , Garcia-Manero Guillermo , Alvarez Ricardo , Kantarjian Hagop M. , Michal Mego , Albarracin Constance , Tang Guilin , Strom Sara S. , Reuben James M. , Khoury Joseph D 
Published: October 2019

Abstract
Introduction: Patients who receive chemotherapy and/or radiation therapy for breast cancer (BCA) are at risk for developing therapy-related myeloid neoplasms (t-MN). In fact, BCA is one of the most common malignant solid tumors among patients with t-MN. Nonetheless, the association between t-MN features and the demographic, biologic, and therapeutic characteristics of patients with BCA remain poorly characterized. The aim of this study was to assess the factors associated with t-MN in BCA patients and determine the features and outcomes of t-MN in this patient group.
Methods: We conducted a retrospective analysis of BCA patients who developed t-MN seen at The University of Texas M.D. Anderson Cancer Center between January 1997 and April 2013. As defined in the current WHO classification, t-MN includes therapy-related acute myeloid leukemia (t-AML), myelodysplastic syndrome (t-MDS), and myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN). The study inclusion criteria included receipt of neoadjuvant or adjuvant chemotherapy and/or radiation therapy for BCA with subsequent development of t-MN.
Results: All patients (n=150) were women with a median age of 57 years (range, 26-79 years) at the time of BCA diagnosis (64 at time of t-MN; range, 29-84 years). At presentation with BCA, stage ranged from 0 to 3. In addition to surgery, 93 (62%) patients were treated with combination chemotherapy and radiation therapy, 30 (20%) with radiation therapy alone, and 27 (18%) with chemotherapy alone. The median interval between BCA and t-MN was 57 months (range, 8-374 months); 54 months and 57 months respectively for patients who received chemotherapy alone or radiation therapy alone. At the time of t-MN diagnosis, 90 (60%) patients had t-AML, 56 (37%) t-MDS, and 4 (3%) t-MDS/MPN. Among patients with t-MDS and t-MDS/MPN, 26 (22%) developed t-AML after a median of 13.9 months (range, 2.3-69.6 months). Notably, development of t-MN among patients with BCA was associated with a body-mass index <25 (p=0.030) and with HER2-positive BCA (14/55; p=0.037). Among all patients with t-MN, those with MLL gene (11q23) rearrangement had a worse overall survival (OS) (p=0.017) while those with favorable recurrent chromosomal translocations (PML/RARA; CBFB-MYH11; RUNX1/RUNX1T1) had a better OS (p=0.001). Patients who received allogeneic stem-cell transplant (SCT) for t-MN had a better OS calculated from the onset of t-MN compared to those who did not (p=0.018). By multivariate analysis, factors associated independently with OS calculated from the time of BCA diagnosis included age at BCA diagnosis (p<0.001), BMI category (p=0.016), chemotherapy for BCA (p=0.027), anti-HER2 therapy (p=0.003), and growth factor administration (p=0.023). Notable factors associated independently with OS calculated from the time of t-MN diagnosis included MLL rearrangement (p=0.014), favorable recurrent balanced translocations (p=0.006), and SCT (p=0.010).
Conclusions: Patients with BCA who have a BMI <25 and are HER2-positive appear to be at a higher risk for t-MN. In addition, the OS of BCA patients in our study group appears to be associated with BMI and anti-HER2 therapy.

Disclosures
No relevant conflicts of interest to declare.