Prognostic Significance of the Tumor-Stromal Ratio in Invasive Breast Cancer and a Proposal of a New Ts-TNM Staging System

Abstract

Background. Previous studies have demonstrated that the tumor-stromal ratio (TSR) was an independent prognostic factor in several types of carcinomas. This study aimed at exploring the prognostic significance of the TSR in invasive breast cancer using immunohistochemistry (IHC)-stained tissue microarrays (TMAs) and integrating the TSR into the traditional tumor-node-metastasis (TNM) staging system. Methods. The prepared 7 TMAs containing 240 patients with 480 invasive BC specimens were stained with cytokeratin (CK) by the IHC staining method. The ratio of tumor cells and stromal cells was visually assessed. TSR > 1 and TSR ≤ 1 were categorized as the high TSR (low stroma) and low TSR (high stroma) groups, respectively, and the prognostic value of the TSR at 5-year disease-free survival (5-DFS) was analyzed. A new Ts-TNM (tumor stroma-tumor-node-metastasis) staging system was established and assessed. Results. IHC staining of CK could specifically label tumor cells with clear contrast, making it easy to manually assess TSR. High TSR (low stroma) and low TSR (high stroma) were observed in 52.5% (n = 126) and 47.5 (n = 114) of the cases, according to the division of value 1. A Kaplan–Meier analysis showed that patients in the low TSR group had a worse 5-DFS compared with patients in the high TSR group (P=0.022). Multivariable analysis indicated that the T stage (P=0.014), N status (P<0.001), histological grade (P<0.001), estrogen receptor status (P=0.015), and TSR (P=0.011) were independent prognostic factors of invasive BC patients. The new Ts-TNM staging system combining TSR, tumor staging, lymph node status, and metastasis staging was established. The receiver operating characteristic (ROC) curve analysis demonstrated that the ability of the Ts-TNM staging system to predict recurrence was not lower than that of the TNM staging system. Conclusions. This study confirms that the TSR is a prognostic indicator for invasive breast cancer. The Ts-TNM staging system containing stromal and tumor information may optimize risk stratification for invasive breast cancer.