Association of tumor immune microenvironment profiling and 21-gene recurrence assay in early breast cancer patients

Abstract

Introduction: Tumor immune microenvironment (TIME) plays a vital role in breast cancer development, treatment resistance, and prognosis. This study evaluates the association of TIME profiling and 21-gene recurrence score (RS) in early Luminal breast cancer patients. Methods: ER+ /HER2-, pN0 breast cancer patients with available RS results who received surgery between January 2009 and December 2013 were enrolled. TIME markers, including stromal tumor infiltrating lymphocytes (TILs), CD3, CD4, CD8, and tumor PD-L1 expression, were comprehensively analyzed. Association of TIME markers with RS, as well as their correlation with breast cancer-specific survival (BCSS) were tested. Results: Overall, 385 patients were included, of whom 341 (88.6%) had TILs ≤10%. TIME markers were positively but moderately correlated with each other (Spearman r 0.28–0.53, all P < 0.05). Continuous RS showed a weak correlation with continuous TILs, CD3, CD8, and PD-L1. Regarding single gene mRNA level in the 21-gene RS panel, higher expression of TIME markers was related to lower ER group genes expression, but higher proliferation and invasion group genes level. After a median follow-up of 91.67 (range 5.03–134.03) months, TILs (P = 0.049) and PD-L1 (P = 0.034) were inversely associated with BCSS. Conclusions: Breast cancer TIME markers, including TILs, CD3, CD4, CD8, and PD-L1, were correlated with 21-gene RS score. Lower expression of ER group genes, as well as higher expression of proliferation and invasion group genes were associated with a higher level of these TIME markers, warranting further exploration.