Whole-lung irradiation associated with greater risk of breast cancer

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1. Compared to lower delivered doses of radiation, whole-lung field radiation for childhood cancer showed a higher risk of breast cancer.

2. Breast cancer-specific mortality following childhood irradiation was substantial.

Evidence Rating Level: 2 (Good)

Study Rundown: Previous studies have established higher risk of breast cancer for women who underwent chest irradiation in childhood, with rates ranging from 5-14% by age 40. Furthermore, it is also known that higher doses of radiation increase the risk. The purpose of this study was to further evaluate risk factors for breast cancer incidence and mortality in this population and the effects of radiation dose and volume of exposed tissue. On analysis, the authors found that the highest risk of breast cancer was associated with lower delivered doses of radiation over larger volumes of breast tissue (whole-lung field), though limited volume was still associated with higher risk. Overall incidence of breast cancer was higher than found in previous studies and breast cancer-specific mortality substantial. Based on these results, the authors suggest that women treated with lower radiation doses or smaller fields may still benefit from early initiation of breast cancer surveillance. It should be noted that the average cohort age was relatively young at 37 years old and that smaller patient numbers in specific sub-groups may limit conclusions based on these results.

Click to read the study in JCO

Relevant Reading: Subsequent malignancies in children treated for Hodgkin’s disease: associations with gender and radiation dose

In-Depth [retrospective cohort]: The study authors drew data from the CCSS (Childhood Cancer Survivor Study) retrospective cohort, which included patients from 26 different institutions. The authors restricted analysis to female patients who underwent chest irradiation within 5 years of childhood cancer diagnosis. The primary outcome measured was confirmed diagnosis of breast cancer. Other outcomes included all-cause mortality subsequent to breast cancer diagnosis and breast cancer-specific mortality at 5 and 10 years. Initial results confirmed that women treated with >20 Gy had high risk of breast cancer, as did those treated with 10-19 Gy (SIR, 30.6; 95% CI, 18.4 to 50.9). Women treated with lower delivered doses but a large volume (whole-lung field) had high risk (SIR, 43.6; 95% CI, 27.2 to 70.3). Overall cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34) with 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast-cancer specific mortality at 5 and 10 years was 12% (95% CI, 8-18) and 19% (95% CI, 13-25). All-cause mortality at 5 and 10 years was 15% (95% CI, 11-22) and 32% (95% CI, 25 to 40). No association between survival and dose of chest radiation was found.

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