Breast composition and dose deposition to fat and fibroglandular tissues are associated with breast side effects after radiation therapy

OBJECTIVE: Breast comprises different tissues with potentially different dose responses to radiation therapy (RT). This study investigates the correlation between RT dose, breast composition, and side effects from breast RT. MATERIAL/METHODS: Data from 922 early-stage breast cancer patients who underwent breast-conserving surgery and RT from the REQUITE study were included. Breast pain, oedema, atrophy, and induration were assessed immediately post-RT, one-year, and two-years post-RT. Maximum severity scores for each toxicity were used for analysis. Breast tissue was divided into "fat" and "fibroglandular" substructures from computed tomography (CT) using a Gaussian Mixture Model. The correlation between breast characteristics, toxicity, dosimetric parameters, and patient and clinical variables was investigated using ordinal regression. The model's fit was evaluated using the Akaike Information Criterion in SPSS v.29. RESULTS: Breast volume and breast density were associated with increased risk of breast oedema, atrophy, and induration in multivariable analysis (p