Cumulative Risk of Breast Cancer Reaches 30% by Age 50 After Chest Irradiation for Childhood Cancer
The incidence of breast cancer in women treated with chest radiation therapy for childhood cancer previously has been estimated at 5% to 14% by age 40 years and is among the highest reported for any population. In a study reported in the Journal of Clinical Oncology, Moskowitz et al found that the cumulative incidence of breast cancer by age 50 was 30% among childhood cancer survivors overall and 35% among those treated for Hodgkin lymphoma. Risk was highest in patients who had received lower doses of radiation to the whole-lung field or high doses of radiation to the mantle field.
Study Details
The study examined cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). Eligibility for participation in the CCSS included diagnosis of cancer before age 21 years, initial treatment between 1970 and 1986, and being alive at 5 years after diagnosis of leukemia, central nervous system tumor, Hodgkin or non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, soft-tissue sarcoma, or bone tumor.
At a median age at last contact of 37 years, 203 women had a confirmed breast cancer diagnosis. The median time from childhood cancer diagnosis to breast cancer diagnosis was 23 years, and the median age at breast cancer diagnosis was 39 years.
Risk Elevations by Field and Dose
Standardized incidence ratios (SIR) for breast cancer compared with expected number of breast cancer cases in the general U.S. population using age- and calendar year-specific rates from the Surveillance, Epidemiology, and End Results (SEER) program were significantly elevated in virtually all categories examined. The entire cohort had a 22-fold increased risk of breast cancer (SIR = 21.9).
According to primary irradiation field and median dose, standardized incidence ratios were 24.2 for mantle field at a median of 40 Gy, 13.0 for mediastinal at 30 Gy, 43.6 for whole lung at a median of 14 Gy, 19.3 for total body at 12 Gy, 10.8 for abdominal at 20 Gy, 0.0 for posterior chest at 31 Gy, and 9.9 for other one-sided anterior field at 41 Gy.
Risk of breast cancer was significantly increased compared with the general population according to dose of 10 to 19 Gy (SIR = 30.6) or ≥ 20 Gy (SIR = 21.2), irradiation (SIR = 8.8) or no irradiation (SIR = 23.7) of ovaries, use (SIR = 21.4) or no use (SIR = 22.7) of alkylating agents, Hodgkin lymphoma (SIR = 23.1) or other cancer (SIR = 17.8), and age at diagnosis of 0 to 9 years (SIR = 14.8), 10 to 14 years (SIR = 27.5), or 15 to 20 years (SIR = 20.6).
Risk Modifiers
Women who had received mediastinal irradiation had a significantly reduced risk of breast cancer vs women receiving similar doses of mantle field radiation (incidence rate ratio adjusted for dose = 0.5, P = .013). Treatment with a radiation field that included the ovaries was associated with reduced risk vs a field excluding the ovaries (adjusted incidence rate ratio = 0.3, P = .003). Risk did not differ according to use or nonuse of alkylating agents.
At 5 and 10 years, all-cause mortality was 15% and 32% and breast cancer-specific mortality was 12% and 19%. There was no difference in survival according to dose of chest radiation.
The investigators concluded, “Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.”
Chaya S. Moskowitz, PhD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by National Cancer Institute grants, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities. The authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
