Clinical value of CTLA4 combined with clinicopathological factors in evaluating the prognosis of breast cancer

Gland Surg. 2020 Oct;9(5):1328-1337. doi: 10.21037/gs-20-359.

Abstract

Background: Clinical prediction of breast cancer prognosis relies on both clinical-pathological features and biological markers. Many studies have revealed that tumor cytotoxic T lymphocyte antigen 4 (CTLA4) expression may present prognostic predicting value in cancers. We intended to explore the prognostic value of significant clinicopathological parameters and CTLA4 for predicting survival of patients with breast cancer.

Methods: A total of 229 breast cancer patients who had radical surgery treatment between Sep 2009 and April 2011 were enrolled in this study. Immunohistochemical staining was performed to evaluate CTLA4 grade and Ki-67 index in breast cancer tissue. Univariate and multivariate logistic analysis, Kaplan-Meier survival analysis and ROC curve were used to explore the association between CTLA4 or clinicopathological parameters and disease-free survival (DFS). A nomogram was constructed based on the regression model to predict DFS of patients with breast cancer.

Results: CTLA4 grade (OR 1.730, 95% CI: 1.213-2.468, P=0.002), Ki-67 (OR 1.449, 95% CI: 1.069-1.964, P=0.017) and N stage (lymph node metastasis) (OR 2.268, 95% CI: 1.588-3.303, P=0.000) showed significantly association with DFS of breast cancer patients. All these factors were independent predictors for poor survival, as patients with stage N2-3 tumors, high CTLA4 grade and Ki-67 index showed low survival probability (P<0.01). The conjunction of these factors exhibited good discrimination value (AUC 0.815, 95% CI: 0.749-0.882, P=0.000). Nomogram performed based on CTLA4 grade, Ki-67 index and N stage provided an efficient method to predict DFS of patients with breast cancer.

Conclusions: The high expression of CTLA4 and Ki-67 together with lymph node metastasis in breast cancer are independent risk factors that affect the prognosis of breast cancer patients. They have the potentiality to be utilized conjunctively as predictor in clinical practice.

Keywords: Breast cancer; Ki-67 index; N stage; cytotoxic T lymphocyte antigen 4 (CTLA4); nomogram.