Multidisciplinary strategies to reduce radiotherapy-induced cardiotoxicity in breast cancer: surgical and technological innovations

Abstract

Radiotherapy remains essential in breast cancer management, yet its long-term cardiotoxicity, driven primarily by radiation-induced myocardial fibrosis, threatens survivorship, particularly in left-sided tumors. Surgical refinements, including breast-conserving surgery with sentinel lymph node biopsy and total mastectomy, effectively reduce radiation fields and cardiac exposure. Intraoperative radiotherapy with lead shielding markedly lowers left anterior descending artery dose from 5.2 Gy to 0.07 Gy. Technological advances-such as deep-inhalation breath-hold, proton therapy exploiting the Bragg peak, and intensity-modulated radiotherapy, further optimize cardiac sparing while preserving oncologic efficacy. Integrating intraoperative image guidance, pharmacological cardioprotection, and AI-assisted planning facilitates precise dose delivery tailored to individual anatomy and risk. This review synthesizes multidisciplinary strategies to mitigate cardiac injury through surgical and technological innovation, underscoring a paradigm shift toward organ-sparing precision radiotherapy. Future directions include the application of degradable shielding materials, senescence-targeted therapies, and predictive modeling to balance therapeutic efficacy with long-term cardiovascular safety in breast cancer care.

Keywords: breast cancer; cardiac protection; cardiotoxicity; radiotherapy; radiotherapy-induced cardiotoxicity.

Figure 1

Pathophysiological mechanisms of radiotherapy-induced cardiotoxicity in breast cancer. This schematic integrates molecular and cellular events driving radiation-induced myocardial fibrosis: Ionizing radiation directly damages cardiomyocytes by triggering TGF-β release and endothelial cells via promoting leukocyte infiltration. Fibroblast activation amplifies collagen I/III deposition, increasing myocardial stiffness and impairing diastolic function. Senescent fibroblasts stabilize HIF-1α via ROS/TGF-β, upregulating profibrotic genes and collagenolytic enzymes that preferentially degrade fragile type III collagen. Myeloid/endothelial-to-fibroblast differentiation exacerbates fibrosis through collagen-enriched microenvironment formation.

Figure 2

Surgical and radiotherapeutic strategies for cardiac risk reduction. Schematic representation of multidisciplinary strategies to reduce cardiac toxicity in breast cancer. Breast-conserving surgery preserves quality of life but increases cardiac radiation exposure. Total mastectomy reduces cardiac radiation dose at the cost of quality of life. Intraoperative radiotherapy enables precise tumor-bed targeting with reduced cumulative radiation dose. Proton therapy achieves favorable dose distribution to minimize cardiac exposure. Sentinel lymph node biopsy avoids regional lymph node irradiation. Intraoperative imaging guidance with artificial intelligence assists clinicians in optimal treatment planning, while the deep inspiration breath-hold technique increases heart-target distance during radiation delivery.