Evaluation of the Role of Claudin-4 Antigen Overexpression in Triple-Negative Breast Cancer Patients: A 5-Year Survival Analysis

Abstract

BACKGROUND & OBJECTIVE: Breast cancer (BC) can be categorized into 4 groups based on molecular and pathological evidence: Luminal A, Luminal B, HER2+ tumors, and triple-negative breast cancer (TNBC). TNBC has a poorer survival rate and a higher chance of recurrence and metastasis compared to other BC types, primarily due to its challenging treatment course. Claudin 4 (CLDN4), a transmembrane protein in tight junctions between cells, has been linked to poor prognosis and faster disease progression in these malignancies. METHODS: Patients previously diagnosed with TNBC and tested for CLDN4 overexpression were contacted for follow-up and to determine disease outcomes. The current health status, cause, and time of death (if applicable) were recorded. Patient files were accessed to obtain information on age, tumor size and grading, lymph node involvement, metastasis, Ki67, and CLDN4 expression. RESULTS: Patients with high CLDN expression showed a significantly lower mortality rate. However, after controlling for other covariates, the hazard ratio (HR) was 0.48 (95CI= 0.13 - 1.27) in the crude model for survival, 0.54 (95%CI = 0.2 - 1.43) when adjusted for age at diagnosis, and 0.58 (95%CI = 0.18-1.82) when adjusted for other covariates. CLDN4 was also not correlated with tumor metastasis (HR=0.64, p=0.203, in the crude model; HR=0.52, p=0.409, when adjusted for other covariates). Patients in the CLDN4 high group had a significantly higher number of tumors >2cm. CONCLUSION: Although previous studies have shown that CLDN4 overexpression worsens TNBC prognosis and increases metastasis or recurrence, the current study found no such association.