Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.
The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.
The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).
The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.
By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.
"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.
Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.
Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."
There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.
The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.