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Keywords:

  • antineoplastic combined chemotherapy protocols;
  • adverse effects;
  • breast neoplasms;
  • drug therapy;
  • acute myelocytic leukemia;
  • myelodysplastic syndromes;
  • chemically induced

Abstract

BACKGROUND

The results of randomized clinical trials have suggested that after receiving radiotherapy and/or chemotherapy, patients with primary breast carcinoma have an increased risk of developing leukemia. In the current study, the authors set out to assess the reported association between breast carcinoma treatment and leukemia risk.

METHODS

A registry of all patients with breast carcinoma who were treated at a community-based institution since 1989 (updated annually for recurrence and/or vital status) was linked to the National Cancer Institute Surveillance, Epidemiology, and End Results database to confirm complete ascertainment of leukemia cases occurring within this registry population. Incidence rates were calculated for women who were treated for primary Stage 0–III breast carcinoma and had a follow-up duration of ≥ 24 months (n = 2866). Patients who did not undergo surgery (n = 5), patients for whom chemotherapy records were incomplete or who received nonstandard chemotherapy regimens (n = 69), patients who underwent stem cell transplantation (n = 83), and patients who were lost to follow-up or who had unknown disease status at follow-up (n = 81) were excluded from the analysis (total, n = 238).

RESULTS

Among patients diagnosed with breast carcinoma between 1992 and 1999, the crude overall leukemia incidence rate was 0.28%, and the acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) incidence rate was 0.11%. The average follow-up duration was 5.46 years (minimum, 2 years). Eight incident cases of leukemia were documented (2 cases of AML, 1 case of acute lymphoblastic leukemia, 1 case of MDS/refractory anemia with excess blasts, 2 cases of chronic myelogenous leukemia, and 2 cases of chronic lymphocytic leukemia). National age-adjusted overall leukemia incidence rates for the period 1996–1998 predict the occurrence of 9 cases (incidence rate, 0.31%) in the current cohort of women ages 21–94 years. The incidence of leukemia by treatment category was as follows: no surgery/no chemotherapy/no radiotherapy, 2 of 154 patients (1.30%); surgery/no chemotherapy/radiotherapy, 4 of 1403 patients (0.29%); surgery/chemotherapy/no radiotherapy, 0 of 352 patients (0%); and surgery/chemotherapy/radiotherapy, 2 of 957 patients (0.21%).

CONCLUSIONS

In contrast to findings reported from previous randomized clinical trials, the authors did not find evidence of increased posttreatment leukemia incidence in association with the use of chemotherapy, including doxorubicin-based regimens. Cancer 2004. © 2004 American Cancer Society.