In an analysis from the Childhood Cancer Survivor Study (CCSS) and the Dutch Hodgkin Late Effects and LATER cohorts reported in the Journal of Clinical Oncology, Moskowitz et al developed a model for predicting the risk of breast cancer among childhood cancer survivors treated with chest radiotherapy, with risk varying considerably based on multiple factors.

Study Details

The study involved a model derivation set of 1,120 female 5-year survivors, including 242 who developed breast cancer, from the CCSS. Median follow-up was 32.3 years, and median attained age was 42 years.

The validation set consisted of 1,207 female 5-year survivors from the CCSS (n = 586), the Dutch LATER cohort (n = 215), and the Dutch Hodgkin Late Effects cohort (n = 226), including 105 with breast cancer. Median follow-up was 18.6 years, and median attained age was 32 years.

Key Findings

Predictive factors identified in the development cohort and included in the model consisted of chest radiation field, exposure to anthracyclines, whether chest radiation was given within 1 year of menarche, age at menopause, and family history of a first-degree relative with breast cancer.

In the development cohort, breast cancer risks were increased for family history (hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.06–2.08) and when chest radiation was given within 1 year of menarche (HR = 1.55, 95% CI = 1.11–2.18). Risks were decreased for smaller chest radiation fields relative to a mantle field (eg, HR for mediastinal field = 0.35, 95% CI = 0.22–0.56) and when there was no onset of menarche vs women still menstruating (HR = 0.38, 95% CI = 0.22–1.03). The hazard ratio for anthracycline use was 1.32 (95% CI = 0.94–1.84).

In the validation cohort, corresponding hazard ratios were 1.08 (95% CI = 0.52–2.00) for family history, 2.13 (95% CI = 1.07–3.88) when chest radiation was given within 1 year of menarche, 0.41 (95% CI = 0.21–0.74) for mediastinal field vs mantle field, and 1.42 (95% CI = 0.49–4.63) when there was no onset of menarche vs women still menstruating. The hazard ratio was 1.83 (95% CI = 1.13–2.97) for anthracycline use. The model exhibited an expected-to-observed ratio of breast cancer cases of 0.92 (95% CI = 0.74–1.16).

Among all survivors, 10-year risk estimates ranged from 2% to 23% for women aged 30 years (receiver operating characteristic area under the curve [AUC] = 0.63, 95% CI = 0.50–0.73) and from 5% to 34% for those aged 40 years (AUC = 0.67, 95% CI = 0.54–0.84).

The lowest 10-year risk was found among women aged < 30 years treated with chest radiation fields other than mantle field, whole-lung field, or total-body irradiation and who never started menstruating or were postmenopausal before age 25 years, were not treated with anthracyclines, and did not have a first-degree relative with breast cancer.

The 10-year risk was highest among women aged > 40 years treated with mantle field radiation within 1 year of menarche, who were still menstruating, and who had a first-degree relative with breast cancer.

The investigators concluded, “Breast cancer risk varies among childhood cancer survivors treated with chest radiation. Accurate risk prediction may aid in refining surveillance, counseling, and preventive strategies in this population.”

Chaya S. Moskowitz, PhD, of the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants, Meg Bertè Owen Fund, American Lebanese Syrian Associated Charities, and Dutch Cancer Society. For full disclosures of the study authors, visit ascopubs.org.