Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies

Abstract

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10–15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST). ILC’s genetic landscape includes mutations in various genes (CDH1, BRCA2, ATM, etc.) and signaling pathways that impact treatment responses, especially in endocrine treatment. Furthermore, the diverse ILC subtypes complicate its management. Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance.