Risk of acute leukemia following epirubicin-based adjuvant chemotherapy: A report from the National Cancer Institute of Canada Clinical Trials Group

Purpose : Cyclophosphamide, epirubicin, and fluorcuracil (CEF), compared with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. has lead to an improvement in relapse-free and overall survival in premenopausal women with node-positive breast cancer. We undertook this analysis to more accurately define the estimate of risk of secondary acute leukemia (sAL) following epirubicin-containing chemotherapy regimens. Patients and Methods: We assessed the conditional probability of sAL among 1,545 women who received adjuvant (n = 1,477) or neoadjuvant (n = 68) chemotherapy in four National Cancer Institute of Canada Clinical Trials Group trials from 1990 to 1999. The risks associated with epirubicin-containing regimens (CEF or epirubicin and cyclophosphamide [EC]) and other regimens (doxorubicin and cyclophosphamide [AC] or CMF) were determined. Results: A total of 10 cases of sAL were observed (eight acute myelogeneous leukemia, two acute lymphoblastic leukemia): seven among women treated with CEF, two who had received AC, and one following CMF. Using competing risk statistics, the conditional probability of sAL was 1.7% (95% confidence interval [CI], 0.5 to 3.6) among 539 women treated with CEF chemotherapy at a follow-up of 8 years, 0.4% (95% CI, 0% to 1.3%) among the 678 who received CMF, and 1.3% (95% Cl, 0% to 4.7%) among the 231 treated with AC. The conditional probability of death from breast cancer at 8 years for the entire group of women treated with epirubicin-containing regimens in all four trials was approximately 34.9%. Conclusion: CEF chemotherapy for breast cancer carries a small increased risk of sAL compared with CMF. These estimates of acute leukemia risk are important in discussing treatment with women, especially patients with a lower risk of death from breast cancer, such as those with node-negative breast cancer.