Acute Myeloid Leukemia and Myelodysplastic Syndrome After Doxorubicin-Cyclophosphamide Adjuvant Therapy for Operable Breast Cancer: The National Surgical Adjuvant Breast and Bowel Project Experience

Purpose: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Materials and Methods: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m2 q 21 days × 4. C was given as follows: 600 mg/m2 q 21 days × 4 (“standard AC”); 1,200 mg2 q 21 days × 2; 1,200 mg/m2 q 21 days × 4; 2,400 mg/m2 q 21 days × 2; and 2,400 mg/m2 q 21 days × 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with o...