Clinical meaning of stromal tumor infiltrating lymphocytes (sTIL) in luminal early breast cancer.

Abstract

572 Background: Luminal breast cancer (BC) is associated with lower immune activation. Although stromal tumor infiltrating lymphocytes (sTIL) are a marker of better prognosis and response in hormone receptor (HR) negative tumors, sTIL predictive and prognostic implications are less clear in luminal BC. Further insights on the clinical correlations of immune microenvironment in luminal disease may facilitate therapeutic improvement and prognostic stratification in these patients. Methods: Observational and single-center cohort of 345 women with early luminal (HR positive, HER2 negative) BC (2012-2020) treated with chemotherapy. Pre-treatment sTIL were determined in the diagnostic biopsy following validated standard methods. The correlation between sTIL and other tumor characteristics were analyzed (Spearman's Rho and Chi-squared tests). Association of sTIL with pathologic complete response (pCR) in patients treated with neoadjuvant chemotherapy (nCT) was evaluated with logistic regression models. Prognostic value of sTIL for overall (OS) or relapse free interval (RFI) was analyzed by Cox regression models. Results: Median age: 50 (range: 24-89); 48.1% premenopausal; 91.3% infiltrating ductal carcinoma; 30.1% grade 3; 87.2% progesterone receptor (PgR)+; 67.5% treated with nCT and 32.8% with adjuvant CT (aCT); 47.6% N0, 32.8% N1, 19.6% N2-3; median ki67: 30% (82.7% >10%). A 29% of patients showed sTIL=0%. Median sTIL infiltration was 5 (Q1-Q3 range [IQR], 0-10), with higher values in premenopausal (p<0.001), grade 3 (p<0.001), N+ (p<0.001) and luminal B tumors (defined as PgR- and/or grade 3 and/or Ki67>15%) (p<0.001). Ki67 was significantly correlated with sTIL (ρ:0.39; p<0.001). The percentage of sTIL was associated with pCR after nCT (OR: 1.045, 95%Ci 1.02-1.07, p=0.001). No prognostic impact of sTIL for OS or RFI was found in luminal A tumors. In luminal B cases (n=286), any grade of lymphocytic infiltration (defined as sTIL > 0%) was associated with a shorter RFI both in univariate (p=0.01) and multivariate Cox models (HR: 4.83, 95%CI 1.28-18.21, p=0.02), with a non-significant trend for poorer OS (p=0.06). Conclusions: In luminal BC, an increased level of sTIL is associated with luminal B subtype characteristics such as higher proliferation, higher tumor grade and nodal involvement. Lymphocytic infiltration has been found to be a predictor of pCR after nCT, but, in contrast with hormone receptor-negative BC, it is also associated with a poorer prognosis for recurrence and a trend towards worse overall survival in luminal B tumors. [Table: see text]