Clinico-pathological characteristics of a distinct tumor phenotype: invasive lobular carcinoma with tubular elements (ILC-TE) in the WSG ADAPTcycle trial.

Background: 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 non-cohesive carcinoma cells mixed with cohesive tubular elements and complete loss of E-cadherin. Cell-cell adhesion is partially restored by switching from an E-cadherin-deficient to a P-cadherin-proficient status (EPS). The prevalence of ILC-TE remains unknown.

Method: Here, we report data from the central pathology review of >4.500 hormone receptor-positive/HER2-negative breast cancer (BC) cases recruited to the 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 clinico-pathological characteristics.

Results: Pure ILC with complete loss of E-cadherin accounted for 630/4619 (13.6%) BC cases. ILC-TE accounted for 47/630 (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 27/35 (77%) cases tested. EPS was detected in 43/47 (91%) ILC-TE cases. EPS was significantly more common in ILC-TE than in classic ILC or other ILC variants (P<0.001). Clinically, ILC-TE was associated with cT1 stage (P=0.023), cN0 status (P=0.024), lower histologic grade (P=0.004) and lower Ki67 (P=0.012). In contrast, solid ILC was associated with higher Ki67 (P=0.006). Following pre-operative endocrine therapy (pET), higher post-pET Ki67 levels were observed in trabecular ILC, solid-papillary ILC and pleomorphic ILC (P<0.001, P=0.006 and P=0.021).

Conclusion: ILC-TE is a quite common ILC variant that is associated with EPS, less aggressive clinical features and slow growth.