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

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.

Keywords: ILC; breast carcinoma; hormone receptor-positive breast cancers; invasive lobular carcinoma; translational medicine; tumor microenvironment.

Figure 1

This figure (left, right) shows two cases of classic ILC (H&E).

Figure 2

This figure shows alveolar ILC (left) (magnification 20×), solid ILC (center) (magnification 20×), and trabecular ILC (right) (magnification 20×).

Figure 3

This figure (left, right) shows two cases of pleomorphic ILC (H&E).

Figure 4

A case of histiocytoid ILC. Magnification (10×).

Figure 5

A case of ILC with signet ring cells. The (top) panel shows H&E images at low power (4×) (left) and high power (right) (magnification 20×) views. The (bottom) picture shows loss of E-cadherin expression.

Figure 6

Loss of E-cadherin expression. Central normal duct showing E-cadherin positivity.

Figure 7

p120 IHC staining. The marked box shows cyto-membranous staining (p-120 IHC) of the tumor cells.