Background: Survivors of childhood cancer are at risk for secondary breast cancer. Other than previous chest radiation therapy, risk factors for secondary breast cancer have not been established.

Objective: To identify risk factors for breast cancer among female survivors of childhood cancer.

Design: Retrospective cohort study.

Setting: The Childhood Cancer Survivor Study (CCSS), a multicenter study of persons who survived more than 5 years after childhood cancer diagnosed from 1970 to 1986.

Participants: Among 6068 women in the CCSS, 95 women had 111 confirmed cases of breast cancer.

Measurements: Standardized incidence ratios for breast cancer were calculated by using age-specific incidence rates in the general population. Breast cancer incidence was evaluated with respect to primary cancer diagnosis and therapy, age at and time since primary diagnosis, menstrual and reproductive history, and family history of cancer.

Results: Breast cancer risk was increased in survivors who were treated with chest radiation therapy (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone and soft-tissue sarcoma who were not treated with chest radiation therapy (standardized incidence ratios, 6.7 and 7.6, respectively). Family history of breast cancer (relative rate, 2.7 [CI, 1.3 to 5.0]) and history of thyroid disease (relative rate, 1.7 [CI, 1.1 to 2.6]) were independently associated with increased risk, and exposure to pelvic radiation was protective (relative rate, 0.6 [CI, 0.4 to 0.9]). Age at primary cancer diagnosis and menstrual and reproductive histories did not statistically significantly modify risk.

Limitations: This cohort has not yet attained an age at which breast cancer risk is greatest.

Conclusion: Survivors of childhood sarcomas and those who received chest radiation therapy are at risk for secondary breast cancer. When assessing a survivor's risk, clinicians should consider primary diagnosis, previous radiation therapy, family cancer history, and history of thyroid disease.