Impact of paclitaxel-, docetaxel- and trastuzumab-based treatment according to Ki-67 and E-cadherin expression in invasive ductal and lobular breast carcinoma

Abstract: Background: Breast cancer is still the most common cause of cancer death all over the world and invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are its two predominant histological subtypes. Ki-67, a marker of cell proliferation and E-cadherin, an essential epithelial cell–cell adhesion molecule, are common prognostic biomarkers that have proven predictive values of response to taxane-based chemotherapy; however, the significance of their gene expression in predicting benefit from taxane therapy across various IDC and ILC subtypes in combination with targeted agents is still less defined. Objectives: This study was conducted to assess the predictive value of Ki-67 and E-cadherin expression for treatment response, progression-free survival (PFS), and overall survival (OS), whereas docetaxel- or paclitaxel-based chemotherapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive cases is used among patients with both IDC and ILC. Methods: The study comprised 200 stage I–III breast cancer patients including 100 IDC and 100 ILC. Tumors were classified into low (30%) based on Ki-67 and E-cadherin expression status, which was evaluated by immunohistochemistry (IHC). All patients received one of the standard taxane-containing chemotherapy regimens with or without trastuzumab for HER2-positive tumors. Eligibility for treatment was not dependent on biomarker status. Tumor responses were determined according to the RECIST criteria and OS was calculated by Kaplan–Meier estimates as well as multivariate Cox regression analysis. Results: Low-dose-treated tumors with low Ki-67 showed significantly higher percent tumor volume reduction (45%) than high Ki-67 tumors (15%; p < 0.01). The rates of complete response (CR) or partial response (PR) were significantly higher in the presence than in the absence of E-cadherin (35% vs 20%; p = 0.04). Patients with a low Ki-67 index had a median PFS of 18 months compared to ≥high Ki-67 group (9 months; p < 0.001). In HER2-positive patients, median PFS was also longer in comparison with HER2-negative controls (22 vs 15 months; p = 0.03). Conclusion: Ki-67 and E-cadherin expression for the prognosis of response as well as survival in patients with IDC and ILC undergoing taxane-based chemotherapy can be independently stratified. These results imply that combining proliferation and adhesion markers may contribute to personalized treatment decision-making beyond their prognostic implications.