Development and validation of prognostic model based on distribution and density of CD3(+) and CD8(+) infiltrating lymphocytes in breast cancer: A multicenter cohort study.

BACKGROUND: The prognostic value of infiltrating lymphocytes distribution and their densities in breast cancer is unknown. This study aimed to develop a tumor immune microenvironment-based model to predict prognosis in early breast cancer patients. METHODS: Densities of CD3(+) and CD8(+) lymphocytes in the core of tumor (CT) and invasive margin (IM) regions were quantified. A combined score of CD3(+) and CD8(+) infiltrating lymphocytes in both CT and IM regions was performed to construct the prognostic immunoindex (PII) as follows, low-PII (score 0), intermediate-PII (score 1 to 2), and high-PII (score 3 to 4). The PII was developed in the training cohort and verified in the internal and external validation cohorts. RESULTS: A total of 1194 patients were included. In the training cohort, a higher 5-year DFS was observed in the high- or intermediate-PII groups compared with the low-PII group (95.1 %, 89.1 %, 83.7 %, respectively, P = 0.008). Patients with a high PII also had the best 5-year OS of 97.5 %, compared to 96.4 % and 92.7 % in the intermediate- and low-PII groups (P = 0.016), which was also found in the internal (P = 0.011 for DFS, P = 0.013 for OS) and external validation cohort (P = 0.010 for DFS, P = 0.143 for OS). PII was shown to be an independent favorable prognostic factor for DFS (P < 0.001) and OS (P = 0.001), especially in HER2-positive (P = 0.009) and triple-negative (P = 0.007) breast cancer patients. CONCLUSION: The PII model can predict survival in breast cancer patients, which might provide a novel risk classification to guide further individualized treatment.