Unique Molecular Alteration of Lobular Breast Cancer: Association with Pathological Classification, Tumor Biology and Behavior, and Clinical Management.

Invasive lobular carcinoma (ILC), accounting for up to 15% of diagnosed breast cancers, has garnered significant attention due to the loss of the epithelial cell-cell adhesion molecule E-cadherin. This loss contributes to its distinct biological, morphological, and clinical characteristics compared to non-lobular breast cancers. The use of immunohistochemistry (IHC) for E-cadherin and/or the associated cadherin-catenin complex, such as p120-catenin and beta-catenin, in morphologically equivocal cases, has been increasingly adopted in pathology practice. This approach has substantially improved diagnostic accuracy, interobserver reproducibility, and the identification of new morphologic variants of ILC. ILCs exhibit unique tumor biology, which presents considerable challenges in clinical management, especially in preoperative imaging evaluation, surgical management, and neoadjuvant treatment. Recent advances in translational and clinical research have enhanced our understanding of ILC and have spurred the development of new clinical trials specifically targeting these cancers. This review highlights recent progress in various aspects of ILC, including its unique molecular alteration, pathological classification and diagnostic approach, tumor biology and behavior, key clinical management challenges, and ongoing clinical trials, as well as the role of artificial intelligence in diagnosing ILC radiologically and pathologically. The goal of this review is to provide an updated understanding of the tumor biology, clinical manifestations, and molecular landscape of ILC and to help refine current tumor classification and diagnosis, subsequently improving management strategies and overall outcomes for lobular carcinoma patients.