Proton Radiation for Locally Advanced Breast Cancer: Evolution and Techniques

Proton therapy has emerged as an important technique for locally advanced breast cancer (LABC), driven primarily by the need to reduce cardiopulmonary dose during comprehensive nodal irradiation, particularly when the internal mammary chain is targeted. Since the first clinical proton experience in patients with LABC and unfavorable cardiac anatomy in 2010, proton radiotherapy for LABC has evolved considerably: delivery technique has progressed from passive scattering and uniform scanning to pencil beam scanning and intensity-modulated proton therapy, while breast radiation oncology overall has shifted from field-based to volumetric, contour-driven planning. X, the first large prospective randomized trial comparing proton and photon regional nodal irradiation, completed accrual in 2024 (n=1,239); its 2025 health-related quality-of-life analysis showed similarly excellent patient-reported outcomes in both arms, while the trial's primary endpoints of loco-regional control and major cardiac events remain pending. Beyond X, most published experience remains single-institutional and technically heterogeneous. This critical review examines the historical development, technical evolution, and clinical application of proton therapy for LABC, with attention to contouring philosophy, robustness evaluation, and optimization of normal tissue-related side effects. Because proton plans are more sensitive to contour accuracy, setup, and range uncertainty than photon plans, and because proton entrance-dose behavior differs fundamentally from the photon skin-sparing effect, target delineation and plan robustness assessment require deliberate, disease-specific decision-making. We provide practical guidance for radiation oncologists, physicists, and dosimetrists, particularly those at centers early in their proton breast experience, and outline priorities for standardized reporting as long-term X outcomes mature.