Risk of Subsequent Breast Cancer in Female Childhood Cancer Survivors
As reported by Ehrhardt et al in the Journal of Clinical Oncology, high doses of anthracyclines were associated with increased breast cancer risk in female childhood cancer survivors in the St. Jude Lifetime Cohort Study, with the association being independent of mutations in cancer risk genes.
Study Details
The study involved 1,467 women who had a median age of 6.9 years (range = 0–22.7 years) at childhood cancer diagnosis and 30.5 years (range = 18.5–64.6 years) at evaluation. Patients underwent risk-based assessments, prior health event validation, chest radiation dosimetry, and whole-genome sequencing. Breast biopsy reports were reviewed. A subgroup of 139 patients underwent both breast magnetic resonance imaging and mammography.
Key Findings
Key findings of the study were as follows:
- Among the 1,467 women, 56 (3.8%) developed 68 breast cancers at a median age of 38.6 years (range = 24.5–53.0 years). The cumulative incidence at age 35 years was 1% among those receiving no chest radiation and 8% among those who received ≥ 10 Gray (Gy) of chest radiation.
- In multivariate analysis, breast cancer was associated with ≥ 20 Gy of chest radiation vs none (hazard ratio [HR] = 7.6, 95% confidence interval [CI] = 2.9–20.4), anthracycline exposure vs none (HR for 1–249 mg/m2 = 2.6, 95% CI = 1.1–6.2; HR for ≥ 250 mg/m2 = 13.4, 95% CI = 5.5–32.5), and presence of a breast cancer predisposition gene mutation (HR = 23.0, 95% CI = 7.3–72.2).
- Anthracycline exposure ≥ 250 mg/m2 remained a significant risk factor in models excluding survivors with cancer predisposition gene mutations, chest radiation ≥10 Gy, or both.
- Sensitivity/specificity for breast cancer detection were 53.8%/96.3% for mammography, 69.2%/91.4% for magnetic resonance imaging, and 85.8%/99.7% for dual imaging.
- Cancers detected by imaging or prophylactic mastectomy vs physical findings were more likely to be in situ carcinomas, smaller, have no lymph node involvement, and to be treated without chemotherapy.
The investigators concluded, “Higher doses of anthracyclines are associated with increased risk of breast cancer independent of mutations in known cancer predisposition genes. Surveillance imaging identifies breast cancers less likely to require chemotherapy than those detected by physical findings.”
Matthew J. Ehrhardt, MD, MS, of the Departments of Oncology and Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a Cancer Center Support Grant to St. Jude Children’s Research Hospital, multiple principal investigators, and the American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
