Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights

SIMPLE SUMMARY: Invasive lobular carcinoma (ILC), the second most common type of breast cancer, is a distinct entity. Despite their unique biology and clinical course, lobular carcinomas have been researched in the broad category of hormone receptor positive breast cancers and these too have been predominated by invasive ductal cancers. With advancements in digital techniques, clinical research targeting ILC specifically is imperative in this era of targeted therapy. In this review, we highlighted the most important recent and relevant developments that have happened in the ILC domain, including histology and integrating advances in genomics and the overall translational medicine aspects of ILC. ABSTRACT: The second most common breast carcinoma, invasive lobular carcinoma, accounts for approximately 15% of tumors of breast origin. Its incidence has increased in recent times due in part to hormone replacement therapy and improvement in diagnostic modalities. Although believed to arise from the same cell type as their ductal counterpart, invasive lobular carcinomas (ILCs) are a distinct entity with different regulating genetic pathways, characteristic histologies, and different biology. The features most unique to lobular carcinomas include loss of E-Cadherin leading to discohesion and formation of a characteristic single file pattern on histology. Because most of these tumors exhibit estrogen receptor positivity and Her2 neu negativity, endocrine therapy has predominated to treat these tumors. However novel treatments like CDK4/6 inhibitors have shown importance and antibody drug conjugates may be instrumental considering newer categories of Her 2 Low breast tumors. In this narrative review, we explore multiple pathological aspects and translational features of this unique entity. In addition, due to advancement in technologies like spatial transcriptomics and other hi-plex technologies, we have tried to enlist upon the characteristics of the tumor microenvironment and the latest associated findings to better understand the new prospective therapeutic options in the current era of personalized treatment.