Breast Cancer Risk After Chest Radiotherapy in Hodgkin Lymphoma Survivors: A Comprehensive Overview

Abstract

Secondary breast cancer (SBC) is emerging as the most frequent solid tumour in female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy (RT). Women irradiated with ≥10 Gy before the age of 30 accumulate risks that rival those carried by BRCA1/2 mutation carriers, with excess cases appearing ∼8 years after RT and persisting lifelong. This review weaves together epidemiological data, mechanistic evidence and clinical studies to elucidate how radiation dose and field, age at exposure, systemic regimens, host genomics and micro-environmental factors interact to drive SBC. Radiation-associated tumours display a distinctive profile-earlier onset, frequent bilaterality-posing unique therapeutic and prognostic challenges. We discuss current surveillance recommendations of annual mammography plus breast MRI from age 25 (or 8 years post-RT) and examine preventive strategies ranging from RT de-escalation and cardioprotective chemotherapy to lifestyle modification and selective chemoprevention. Finally, we highlight emerging imaging and molecular biomarkers-most notably MRI background parenchymal enhancement and polygenic risk scores-that may enable a shift from 1-size-fits-all follow-up to precision survivorship care.

Keywords: Background parenchymal enhancement; MRI; Screening; Secondary breast cancer; Survivorship.