Radiation therapy for lobular breast cancer: opportunities and challenges for leveraging radiosensitivity

Invasive lobular carcinoma (ILC) is the most common special histological subtype of breast cancer, accounting for 15% of cases. ILC has unique clinical and molecular characteristics yet is treated largely agnostic of subtype. We explore challenges and opportunities in treating ILC, focusing on the underexplored sensitivity of ILC to ionizing radiation therapy (XRT). While ILC presents forms of resistance to chemotherapy and endocrine therapy, clinical data support that ILC have a distinct vulnerability to XRT, with XRT reducing recurrence rates in postsurgical contexts; molecular analyses identify putative defects in DNA repair in ILC that may underpin XRT sensitivity. However, gaps in the literature limit our understanding of XRT efficacy in ILC, and current treatment guidelines that inadequately address ILC-specific considerations limit XRT optimization. Future research should prioritize new clinical and mechanistic analyses of XRT efficacy, toward optimizing patient care and harnessing the full therapeutic potential of XRT for ILC.