Ehrhardt MJ, et al. - Because TP53 mutation-related gene-environment interactions are presumed to be the mediators of anthracycline-associated risk for subsequent breast cancer in childhood cancer survivors, researchers used the St. Jude Lifetime Cohort to characterize treatment/genetic risks and the influence of screening for breast cancer. They found that an increased risk of breast cancer was present in relation to higher doses of anthracyclines, which was independent of mutations in known cancer predisposition genes. They noted a lower likelihood of requiring chemotherapy in breast cancers detected by surveillance imaging vs breast cancers detected by physical findings.

Methods

• Risk-based evaluations, prior health event validation, chest radiation dosimetry, and whole-genome sequencing were performed in a cohort of female participants.
• Researchers reviewed breast biopsy reports.
• Both breast magnetic resonance imaging and mammography were performed in a subgroup of 139 participants.
• They calculated HRs and 95% CIs by using multivariable regression.

Results

• A total of 68 breast cancers were found to be developed at a median age 38.6 years among 56 of 1,467 included women.
• At age 35 years, 1% (no chest radiation) and 8% (≥ 10 Gy of chest radiation) were the cumulative incidences.
• The associations of breast cancer with ≥ 20 Gy of chest radiation vs none, anthracycline exposure vs none, and having a breast cancer predisposition gene mutation were evident in adjusted models.
• In models excluding survivors with cancer predisposition gene mutations, chest radiation 10 Gy or greater, or both, a significant association of anthracyclines 250 mg/m² or greater with increased risk of breast cancer was evident.
• Anthracyclines ≥ 250 mg/m² remained significantly linked to increased breast cancer risk in models excluding survivors with cancer predisposition gene mutations, chest radiation ≥ 10 Gy, or both.
• Sensitivity/specificity were 53.8%/96.3%, 69.2%/91.4%, and 85.8%/99.7% for mammography, magnetic resonance imaging, and dual imaging, respectively.
• Breast cancers detected via imaging and/or prophylactic mastectomy vs physical findings were more likely to be in situ carcinomas, smaller, without lymph node involvement, and treated without chemotherapy.