Abstract P6-06-17: Assessment of TILs, PDL1 and FOXP3 expression in metaplastic breast cancer: A glimpse into its tumour microenvironment

Abstract

Abstract BACKGROUND: Metaplastic breast carcinoma (MBC) encompasses a heterogeneous group of tumours that differentiate into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements.Tumour cells,among others in the tumour microenvironment express Program Death Ligand 1 (PD-L1); an emerging therapeutic target. Activation of PD-1/PD-L1 pathway in neoplastic cells results in dampening of immune response.FOXP3 is a transcriptional factor for regulatory T-cells associated with immunosuppression. AIMS:We aimed to evaluate the immunohistochemical expression of PD-L1, FOXP3 and tumour infiltrating lymphocytes (TILs) by assessing their expression in tumour and immune stromal cells and correlated this with patient outcome. METHODS:Quantification of TILs according to the 2014 working group was performed for a large cohort of MBC, and control Triple Negative breast cancer (TNBC) cohort. Expression of PD-L1 and FOXP3 was evaluated with immunohistochemistry. PD-L1 expression was recorded in the tumour cells and stromal TILS (sTILs). TILs in direct contact with malignant cells are classed intra-tumoural (iTILs),while sTILs are lymphocytes that do not interact directly with cancer cells. FOXP3 positive iTILs and sTILs were evaluated. Histologic score was calculated and findings compared with the TNBC cohort. RESULTS: No significant associations were found between TILs and World Health Organisation (WHO) MBC subtypes,or number and type of morphologies present in mixed MBCs. However, WHO MBC Types 1 and 4 tend to contain higher amounts of TILs, while WHO Type 6 presents with the least amount of infiltrate, suggesting a restricted immunogenic repertoire. Mixed MBC cases with more than 3 phenotypes present have fewer TILs. Low tumour and high sTILs PD-L1 expression displayed the best clinical outcome (without reaching significance in a Kaplan Meier survival analysis; p value= 0.5780) while FOXP3 iTILs is associated with adverse prognostic outcome (p value=0.0240). CONCLUSIONS: We identified a subset of patients that would likely respond to immunotherapeutics targeting the PD-1/PD-L1 checkpoint. We report the biological significance of FOXP3 and TILs in MBC; wherein, their presence establishes a potential prognostic value. Citation Format: Emarene Mationg Kalaw. Assessment of TILs, PDL1 and FOXP3 expression in metaplastic breast cancer: A glimpse into its tumour microenvironment [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 P6-06-17.