LEUKEMOGENIC POTENTIAL OF ADJUVANT CHEMOTHERAPY FOR EARLY-STAGE BREAST-CANCER - THE EASTERN-COOPERATIVE-ONCOLOGY-GROUP EXPERIENCE

Purpose: Since large numbers of patients with early-stage-breast cance r now receive adjuvant chemotherapy containing cyclophosphamide, a kno wn leukemogenic agent, it is important to determine the risk of second ary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). T herefore, we identified all cases of AML or MDS developing in patients treated on six clinical adjuvant chemotherapy trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and Methods: The patient population included 2,638 patients with previously untreated p rimary operable breast cancer entered onto six clinical trials conduct ed by the ECOG between 1978 and 1987. There are 19,200 person-years of follow-up study and a mean follow-vp duration of 7.3 years. Clinical data were obtained from flow sheets submitted to the ECOG Data Managem ent Office. Results: Of 2,638 patients at risk with 19,200 person-year s of follow-up study, three patients developed MDS (two with a charact eristic cytogenetic abnormality). Two patients developed acute leukemi a; however, one had adult T-cell leukemia associated with human T-lymp hotrophic virus type 1 (HTLV-1) and a second patient developed AML aft er receiving additional cyclophosphamide for metastatic breast cancer. The estimated incidence rate for MDS is three per 19,200 or 16 per 10 0,000 person-years of follow-vp study with a 95 percent confidence int erval of three to 46 per 100,000 person-years. If all five patients (t hree MDS and two acute leukemia) are included, the estimated incidence rate is five per 19,200 or 26 per 100,000 person-years of follow-up s tudy with a 95 percent confidence interval of eight to 61 per 100,000 person-years. Conclusion: These data suggest that the risk of secondar y AML or MDS among patients with early breast cancer who receive stand ard-dose cyclophosphamide-containing adjuvant chemotherapy is not much higher than in the general population. However, physicians must remai n alert to the possible long-term consequences of alkylating agent and anthracycline-based chemotherapy. (C) 1995 by American Society of Cli nical Oncology.