Breast cancer radiotherapy and the risk of lung injury: Advances and perspectives

Breast cancer is the most prevalent malignancy among women worldwide, and radiotherapy (RT) plays a central role in reducing local recurrence and improving survival. Technological advances such as three-dimensional conformal RT (3D-CRT), intensity-modulated RT (IMRT), volumetric-modulated arc therapy (VMAT), and particle therapies have enhanced dose conformity and reduced exposure to surrounding healthy tissues, particularly the lungs. Nevertheless, radiation-induced lung injury (RILI) remains a clinically relevant concern because of the close anatomical relationship between the breast and lung. RILI is a biphasic process, comprising early radiation pneumonitis and late radiation-induced pulmonary fibrosis, with severity influenced by dose distribution and treatment modality. While 3D-CRT carries a moderate risk due to limited beam modulation, IMRT and VMAT improve target coverage but may increase low-dose exposure to larger lung volumes, potentially increasing the risks of subclinical injury and, in the long term, secondary malignancy. Adjunctive lung-sparing strategies, including deep inspiration breath-hold and image-guided techniques, further reduce pulmonary dose. Proton beam therapy, particularly pencil beam scanning, offers additional lung protection through Bragg peak-based dose deposition, minimizing exit dose and irradiation of non-target tissues. Early clinical data suggest a lower incidence of RILI with PBT, although long-term outcomes remain under investigation. Carbon ion RT remains investigational in breast cancer. This review summarizes current evidence on RILI risk across modern RT modalities. A deeper understanding of modality-specific risks is essential for guiding personalized treatment planning and implementing effective lung-sparing strategies.