The predictive value of serum soluble E-cadherin levels in breast cancer patients undergoing preoperative systemic chemotherapy

Abstract

Objectives: To date, no reliable markers are available to predict response to or to assess prognosis after preoperative systemic chemotherapy (PST) in patients with locally advanced breast cancer. Previous studies demonstrated that elevated levels of soluble E-cadherin (sE-cadherin), a product of proteolytic cleavage of cell surface E-cadherin, are associated with higher risk for metastatic disease and poor prognosis in various tumor types. We, therefore, hypothesized that serum sE-cadherin levels measured before PST may correlate with pathological response.

Design and methods: In a retrospective analysis, sE-cadherin levels were measured in sera of 108 female patients with histologically proven breast cancer before initiation of PST by using a commercially available quantitative sandwich enzyme immunoassay technique. Patients received a median number of 4 (range 3-6) cycles of anthracyline-based chemotherapy. The median patient age was 51.5 (range 21-71) years. Tumor size was measured clinically and translated into the tumor-node-metastasis (TNM)-system before the start of chemotherapy. Histopathological response in surgically removed specimens was evaluated using a modified Sinn regression score. In univariate analyses the correlations between levels of sE-cadherin and pathological response to PST were calculated.

Results: The histopathological regression scores correlated significantly with tumor grading (p=0.045), clinical lymph node status before PST (p=0.031) and sE-cadherin levels (p=0.039). No correlation was seen between histopathological regression scores and hormone receptor and menopausal status as well as Her2-neu status.

Conclusion: sE-cadherin may be a marker predicting response to PST for patients with breast cancer. Our findings warrant further evaluation of sE-cadherin in a prospective trial.

Keywords: ADAM; Breast cancer; Chemotherapy; DFS; ERK; Erb-B; HER; MMP; OS; PST; Predictive marker; Preoperative; Serum; Soluble E-cadherin; TNM-system; a disintegrin and metalloproteinase; cT; clinically measured tumor size; disease-free survival; extracellular-signal-regulated kinase; human epidermal growth factor receptor; matrix-metallo-proteinase; overall survival; pCR; pathologic complete remission; preoperative systemic therapy; receptor tyrosine kinase; tumor–node–metastasis cancer staging system.