Validated Breast Cancer Risk Prediction Model Created for Survivors of Pediatric Cancer Treated With Chest Radiation

Contemporary Concepts | <b>Contemporary Concepts in Breast Cancer</b>

Breast cancer risk was estimated among survivors of pediatric cancer who were treated with chest radiation with a newly developed and validated breast cancer risk prediction model.

A validated breast cancer risk prediction model was developed to allow for personalized risk assessment of pediatric cancer survivors who were treated with chest radiation, according to a report published in the Journal of Clinical Oncology.

For women who were 30 years old, the 10-year risk estimates ranged from 2% to 23% (area under the curve [AUC], 0.63; 95% CI, 0.50-0.73). For women who were 40 years old, the estimates ranged from 5% to 34% (AUC, 0.67; 95% CI, 0.54-0.84). Investigators noted that the highest risks were observed in 40-year-old women who had underwent treatment with mantle field radiation within a year of menarche and had a first degree relative who had been diagnosed with breast cancer.

“We derived and validated, what is to our knowledge, the first personalized breast cancer risk prediction model for female childhood cancer survivors treated with chest radiation, a very high-risk population,” the investigators wrote. “The model was developed and validated using data from some of the largest, well-characterized cohorts of childhood cancer survivors available.”

Risk factors for candidates of the model included 3 areas: primary cancer and treatment, hormonal-related risk factors, and other information. Primary cancer and treatment featured diagnosis and age at diagnosis, primary and boost chest radiation fields, doses delivered, and age at radiation and chemotherapy. Hormonal-related risk factors included menarche and menopause age, first live birth age, treatment timing in respect to menarche, and hormone replacement therapy. Other information included family history of breast cancer, breast biopsies, obesity, and race and ethnicity.

The analysis included a total of 2147 female survivors of childhood cancer who were treated with chest radiation, of whom 347 were diagnosed with breast cancer. For women who were alive at last contact in the development cohort, the median follow-up was 32.3 years (range, 9.7-45.7) compared with 18.6 years (range, 6.3-46.0) in the validation cohort. The median time since beginning chest radiation therapy was 29.6 years (range, 2.5-45.6) in the development cohort and 16.6 years (range, 2.1-47.2) in the validation cohorts.

Increased relative risks were observed in variables including family history (HR, 1.48; 95% CI, 1.06-2.08) and chest radiation given within 1 year of menarche (HR, 1.55; 95% CI, 1.11-2.18). Relative risks were decreased for variables such as smaller chest radiation fields (HR, 0.35; 95% CI, 0.22-0.56) and no onset of menarche (HR, 0.38; 95% CI, 0.22-1.03).

The model displayed good calibration, with a ratio of expected to be observed number of breast cancer cases (E/O ratio) of 0.92 (95% CI, 0.74-1.16). Further, E/O ratios were not significantly different between subgroups, although results should be interpreted cautiously due to small sample sizes in each subgroup analysis.

“We developed a model that estimates the personalized risk of breast cancer for women treated with chest radiation for a childhood cancer and validated it on international cohorts. Studies of the utility of incorporating this tool when counseling women or refining breast cancer surveillance in this population are warranted,” the investigators concluded.


Moskowitz CS, Ronckers CM, Chou JF, et al. Development and validation of a breast cancer risk prediction model for childhood cancer survivors treated with chest radiation: A report from the childhood cancer survivor study and the Dutch Hodgkin late effects and LATER cohorts. J Clin Oncol. 2021;39(27):3012-3021. doi:10.1200/JCO.20.02244