Abstract P1-05-07: microRNAs regulating tumor and immune cell interactions in the prediction of early relapse in breast cancer

Abstract

Background: Metastasis remains the major lethal consequence in the progression of early breast cancer (BC). Effective immunosurveillance can inhibit metastasis, while a dysfunctional immune system can create a favorable environment for tumor spread. MicroRNAs (miRNAs) are involved in the regulation of immune response and there is evidence that they play an important role in immune escape. We investigated the effect of plasma miR-10b, miR-126, miR-19α, miR-20α and miR-155, which regulate the interaction between cancer and immune cells during immunosurveillance and immune evasion in patients with early BC. Methods: Blood samples were obtained from relapsed (n=52) and non-relapsed (n=100) patients with early BC before adjuvant chemotherapy. Plasma miRNA expression levels were assessed by qRT-PCR and expression was classified as high or low according to the median values. Receiver operating curves (ROC) were constructed to determine miRNA sensitivity and specificity. Results: miRNA expression was not correlated with patients’ characteristics or outcome. No differences in miRNA expression were observed between relapsed and non-relapsed patients. In multivariate analysis the number of infiltrated axillary lymph nodes and stage III disease independently predicted for shorter DFS (HR: 2.591; p=0.002) and OS (HR: 2.344; p=0.035), respectively. miR-126, miR-20a, miR-19a and miR-155 expression levels were lower in patients with early relapse (defined as relapse at ≤ 2 yrs; n=19) compared to those who either relapse later than 2 years (n=33) or those who remained disease-free during follow up (n=100). ROC curve analysis showed that miR-155 had the highest performance to discriminate patients with early relapse [AUC 0.825; sensitivity 90%, specificity 67% (p<0.001; 95% CI: 0.742-0.909)]. Multivariate analysis revealed that ER negative status and miR-155 low expression independently predicted for shorter DFS (HR: 2.616; p=0.039 and HR: 9.104; p=0.003, respectively). For the triple negative subgroup (n=31), low miR-155 expression was associated with both shorter DFS and OS (p=0.02 and p=0.032, respectively) and low miR-155 expression was an independent predictor of shorter DFS (HR: 5.056; p=0.037). Conclusions: Deregulated expression of circulating miRNAs involved in tumor and immune cell interactions evaluated before adjuvant chemotherapy is associated with early relapse in patients with primary BC. Low miR-155 expression has high accuracy in the prediction of early relapse in the whole group of patients and independently predicts for shorter DFS in the triple negative subgroup. The role of miR-155 in the pathogenesis and management of early relapse in BC merits further investigation. Citation Format: Konstantina Thomopoulou, Chara Papadaki, Alexia Monastirioti, George Koronakis, Lambros Vamvakas, Maria A Papadaki, Sofia Agelaki, Dimitrios Mavroudis. microRNAs regulating tumor and immune cell interactions in the prediction of early relapse in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-07.