Risk of Leukaemia in Ovarian Tumour and Breast Cancer Patients Following Treatment by Cyclophosphamide

A case-control study was conducted to determine whether the development of leukaemia was associated with chemotherapy for neoplasms of the ovary or breast, in a population where most such chemotherapy consisted of cyclophosphamide alone. Cases and controls were identified from the National Cancer Registry of the German Democratic Republic. Cases were women who had developed leukaemia as a second primary after an initial diagnosis, at least one year before, of an ovarian or breast tumour. Controls were patients with an ovarian tumour or breast cancer who had survived to the year when the case developed a leukaemia but who had not themselves developed a second malignancy. Controls were matched to cases by the site of the first primary and its year of diagnosis, as well as year of birth. The relative risk for acute leukaemia following treatment with cyclophosphamide alone was significantly elevated (P less than 0.05), at 14.6 for ovarian tumour patients and 2.7 for breast cancer patients. Among breast cancer patients the increased risk of leukaemia associated with chemotherapy was confined to women who had been under 50 years of age at the time of diagnosis of the breast cancer (for whom the relative risk was 13.1). No excess risk of leukaemia was observed in association with radiotherapy for either ovarian or breast cancer patients. The present findings strongly suggest that cyclophosphamide as a single chemotherapeutic agent is capable of inducing leukaemia in humans.