Abstract P2-08-14: Effect of markers of systemic inflammation on tumor infiltrating lymphocytes in patients with non-metastatic triple negative and HER2+ breast cancer: A single center retrospective study
Authors: Chen Nan , Bulsara Shaun , Hilsenbeck Susan , Hoyos Valentina 
Published: March 2022

Abstract
Background: Tumor infiltrating lymphocytes (TILs) are increasingly being recognized as a vital component of the tumor immune microenvironment. TILs have also been established as a predictive biomarker for response to neoadjuvant therapy in triple negative (TNBC) and HER2+ breast cancer. The relationship between TILs and the systemic immune environment remains poorly understood. Metabolic syndrome and other states of inflammation create dynamic changes in systemic immunity. We hypothesize that the presence of systemic inflammation as measured by hematologic markers and features of metabolic syndrome affects the quantity of TILs in non-metastatic TNBC and HER2+ breast cancer. Methods: A retrospective chart review was conducted in the Harris County Health System to examine the correlation of baseline markers of systemic inflammation to quantity of TILs at the time of breast cancer diagnosis. 141 patients with TNBC and HER2+ breast cancer with evaluable TILs were identified between 2018 and 2020. Body mass index (BMI), Hemoglobin A1C (HgbA1C), low density lipoprotein (LDL), neutrophil lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) were collected as markers of metabolic syndrome and inflammation within ≤ 6 months prior to diagnosis. TILs were categorized as low (0-10%), moderate (10-60%), and high (greater than 60%) and measured by one expert pathologist at our center. Results: The average age at diagnosis was 51.9 years (range 32-74). 64 (45.3%) patients had TNBC while 77 (54.6%) had HER2+ disease, of these patients, 46 (59.7%) were also estrogen receptor (ER) positive. 97 (68.8%) patients were Hispanic, 38 (26.9%) were African American. 46 (32.6%) patients had stage II disease, 79 (56%) patients had stage III disease. In measurement of TILs, 73 (57.8%) patients were categorized as low, 56 (39.7%) as moderate, and 12 (8.5%) as high. Diabetes mellitus as measured by HgbA1C ≥ 6.5% or fasting glucose ≥ 200 (adjusted odds ratio (OR) 1.32 95% CI 0.5-3.4), hyperlipidemia as measured by LDL ≥ 129 (OR 1.27 95% CI 0.55-2.9), and elevated BMI ≥ 25 (OR 1.08 95% CI 0.35 - 3.6) were associated with increased TILs. PLR ≥ 130 was most strongly associated with increased TILs (OR 1.93 95% CI 0.87 - 4.35, p-value 0.11). NLR ≥ 2.5 did not correlate with amount of TILs (OR 1.01 95% CI 0.44 - 2.29). None of the odds ratios were statistically significant, with p values ≥ 0.05. Discussion: Overall, markers of inflammation correlated with increased amount of TILs. Metabolic syndrome, as measured by elevated BMI, presence of diabetes mellitus, and presence of hyperlipidemia as well as hematologic marker of inflammation PLR, demonstrated varying degrees of correlation to increasing TILs without statistical significance. PLR ≥ 130 demonstrated the strongest correlation with increased TILs with a p value of 0.11. This retrospective study is limited by the small patient population, however these results suggest that systemic inflammation as measured by metabolic syndrome and hematologic markers may correlate with higher TILs and thus these patients may demonstrate improved response to neoadjuvant therapy. Larger patient samples may be needed to reach statistical significance and continued data collection is underway.
Citation Format: Nan Chen, Shaun Bulsara, Susan Hilsenbeck, Valentina Hoyos. Effect of markers of systemic inflammation on tumor infiltrating lymphocytes in patients with non-metastatic triple negative and HER2+ breast cancer: A single center retrospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-14.