Increased Breast Cancer Risk Reported in Childhood Sarcoma and Leukemia Survivors With No History of Chest Radiotherapy
In an analysis of the Childhood Cancer Survivor Study reported in the Journal of Clinical Oncology, Henderson et al found that childhood survivors of sarcoma and leukemia with no history of chest radiotherapy were at an increased risk of breast cancer.
Increased Risk
The study included data from 3,768 female childhood cancer survivors without a history of chest radiotherapy. At a median follow-up of 25.5 years (range = 8–39 years), 47 women developed breast cancer (41 invasive, 6 ductal carcinoma in situ) at a median age of 38.0 years (range = 22–47 years) and at a median of 24.0 years (range = 10–34 years) from diagnosis of primary cancer.
Overall, the standardized incidence ratio (SIR) for breast cancer vs the general population was 4.0 (95% confidence interval [CI] = 3.0–5.3). Risk was highest among sarcoma (SIR = 5.3, 95% CI = 3.6–7.8) and leukemia (SIR = 4.1, 95% CI = 2.4–6.9) survivors; no other primary cancer diagnosis was associated with a significantly increased risk. The cumulative incidence of breast cancer by age 45 years was 5.8% in sarcoma survivors and 6.3% in leukemia survivors.
Alkylator and Anthracycline Dose
On multivariate analysis, increasing doses of alkylating agents (P = .044 overall; relative SIR = 3.0, 95% CI = 1.2–7.7, for ≥ 18,000 vs 0 mg/m2 cyclophosphamide equivalent dose) and anthracyclines (P = .004 overall; relative SIR = 3.8, 95% CI = 1.7–8.3, for ≥ 250 vs 0 mg/m2) were significantly associated with breast cancer risk. Analysis restricted to sarcoma and leukemia survivors showed that alkylators and anthracyclines were associated with breast cancer risk in a dose-dependent manner (P < .01 for trend for both).
The investigators concluded: “Women not exposed to chest radiotherapy who survive childhood sarcoma or leukemia have an increased risk of breast cancer at a young age. The data suggest high-dose alkylator and anthracycline chemotherapy increase the risk of breast cancer. This may suggest a possible underlying gene-environment interaction that warrants further study.”
The study was supported by the National Cancer Institute and the Meg Berté Owen Foundation.
Tara O. Henderson, MD, MPH, of the University of Chicago Comer Children’s Hospital, is the corresponding author of the Journal of Clinical Oncology article.
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