Clinicopathological Characteristics of a Distinct Tumor Phenotype: Invasive Lobular Carcinoma With Tubular Elements in the West German Study Group ADAPTcycle Trial

Abstract

Invasive lobular carcinoma with tubular elements (ILC-TE) is a recently identified variant of invasive lobular breast carcinoma (ILC). The histology of ILC-TE is defined by noncohesive carcinoma cells mixed with cohesive tubular elements and complete loss of epithelial (E)-cadherin. Cell–cell adhesion is partially restored by switching from an E-cadherin–deficient to a placental (P)-cadherin–proficient status (EPS). The prevalence of ILC-TE remains unknown. Here, we report data from the central pathology review of >4500 hormone receptor–positive/HER2-negative breast cancer (BC) cases recruited to the West German Study Group (WSG) ADAPTcycle trial (NCT04055493). The central pathology review included prospective assessment of BC types, variants, and E-cadherin expression. Cases classified as ILC-TE were analyzed for their molecular features and clinicopathological characteristics. Pure ILC with complete loss of E-cadherin accounted for 630 of 4619 (13.6%) BC cases. ILC-TE accounted for 47 of 630 (7.5%) lobular carcinomas, making it more than twice as prevalent as mixed BC (NST/ILC). ILC-TE harbored deleterious CDH1/E-cadherin mutations in 27 of 35 (77%) cases tested. EPS was detected in 43 of 47 (91%) ILC-TE cases. EPS was significantly more common in ILC-TE than in classic ILC or other ILC variants (P < .001). Clinically, ILC-TE was associated with cT1 stage (P = .023), cN0 status (P = .024), lower histologic grade (P = .004), and lower Ki67 (P = .012). In contrast, solid ILC was associated with higher Ki67 (P = .006). Following preoperative endocrine therapy, higher post–preoperative endocrine therapy Ki67 levels were observed in trabecular ILC, solid-papillary ILC, and pleomorphic ILC (P < .001, P = .006, and P = .021, respectively). In summary, ILC-TE is a quite common ILC variant that is associated with EPS, less-aggressive clinical features, and slow growth.