Abstract P6-14-13: Association of baseline tumor-infiltrating lymphocytes and cell-cycle regulation markers on prognosis and mortality in patients with advanced breast cancer according to tumor characteristics and treatment type
Authors: Vuoti Sauli , Saari Minna , Narasimha Kumar , Reinikainen Kai 
Published: March 2023

Abstract
We aimed to analyze the expression of cell-cycle regulation markers – minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) and tumor-infiltrating lymphocytes (TILs) in pre-treatment core-biopsy samples of advanced breast carcinomas (ABC) in correlation with known predictive and prognostic factors. Consecutive breast cancer patients (n=398) treated during 2015-2019 were retrospectively analyzed. ABC was defined either as the first indication for locally recurrent, locally advanced or metastatic disease. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs &gt;15%. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, TILs, treatment type (chemotherapy-containing or non-chemotherapy). Univariate and multivariate analyses were used to assess factors associated with disease-free survival (DFS) and overall survival (OS). The multivariate analysis showed that patients with higher TIL levels had an improved 3-year DFS compared with those with low TIL levels, (79.5% vs. 63.7%, HR = 0.52, 95% CI = 0.32–0.78, p = 0.005), which may imply using the biomarkers to indicate initial treatment selection at the advanced stage. The effect was the most pronounced for triple-negative breast cancer (TNBC), and higher for HER2+ than hormone receptor positive breast cancer (HR+). Hormone receptor negative tumors showed significantly higher expression of the studied cell-cycle regulation markers Ki-67, MCM2 and Cyclin A compared with HR+ breast cancer, with TNBC showing the highest activity. Ki-67 and MCM2 were significantly associated with worse prognosis in HR+ breast cancer (p = 0.03; p = 0.04). Treatment type (chemotherapy vs. non-chemotherapy) as the initial treatment at the advanced stage influenced the 3-year DFS and OS in patients with high TIL levels in all molecular breast cancer subtypes. For those with low levels of TILs the difference was statistically non-significant. Our study showed that TIL and cell cycle marker testing could help to identify patients with more aggressive tumor types and the requirement of more aggressive treatment upfront. The proposed biomarker testing can help in selecting the appropriate treatment for increased disease-free survival.
Citation Format: Sauli Vuoti, Minna Saari, Kumar Narasimha, Kai Reinikainen. Association of baseline tumor-infiltrating lymphocytes and cell-cycle regulation markers on prognosis and mortality in patients with advanced breast cancer according to tumor characteristics and treatment type [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-13.