Abstract P1-09-01: Combination of tumor-infiltrating lymphocytes (TILS) and tumor-stroma ratio (TSR) in breast cancer: utility to guide clinical treatment of breast cancer

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Abstract Introduction: Breast cancer is the most common malignant tumour in women and the leading cause of death among them. The incidence rate of breast cancer among women surpassed that of lung cancer in 2020, making it the most common neoplasm in the world, with the exception of non-melanoma skin cancer. The most common histological type is non-special invasive carcinoma (SOE - formerly known as infiltrating ductal carcinoma). Our study highlights the need for new indicators to guide clinical treatment, as the response of breast cancer to anti-HER2 target therapy may be affected by the level of TILs in the carcinoma. The research evaluates the Tumor-Stroma Ratio (TSR) and Tumor Infiltrating Lymphocytes (TILs) in order to identify possible prognostic indicators in malignant tumours. Methods: 130 cases of patients with invasive breast carcinoma diagnosed and treated at IBCC - Instituto Brasileiro de Controle do Câncer, São Paulo, SP - Brazil, from 2003 to December 2013 were collected. The patients' clinical and pathological data was collected, including age, tumour block diameter, number of positive lymph nodes and histological grade. The most significant sample (invasive area) was selected from the tumour with the highest stromal proportion, and multiple sections were taken from this site. The assessment of sTILs (Stromal Tumor Infiltrating Lymphocytes) followed the recommendations of the International TILs Working Group (ITWG). SPSS 23.0 software was used for the statistical analysis, and Pearson's χ2 test and Fisher's exact probability method were performed. Results: Analysis of the results of the clinical pathological characteristics and other study items for the selected samples showed that among the 130 cases of primary breast cancer, from the perspective of the tumor-stroma ratio (TSR), there were 73 cases (56.15%) classified as TSR≥50% (high stroma group) and 57 cases (43.85%) with TSR<50% (low stroma group). As for the study of stromal tumor infiltrating lymphocytes (sTILs), there were 77 cases (59.23%) in the low sTILs group and 53 cases (40.77%) in the high sTILs group. As for patients with metastatic cancer, a total of 38 cases were selected, of which 24 cases (63.15%) had TSR≥50% (high stroma group) and 14 cases (36.85%) with TSR<50% (low stroma group). Kaplan-Meier survival analysis was used to compare the relationship between TSR and TILs in patients with primary breast cancer, with a lower prognostic outlook being found in the low stroma group. The single Cox factor analysis showed that the overall survival rate and disease-free survival rate of patients in the low stroma group were higher than those in the high stroma group. Cox multivariate analysis showed that TSR in tumors can be considered an independent risk factor for patients' overall survival and disease-free survival. Discussion: The study discusses the complex interaction between tumour and non-tumour cells in the stroma, which is mainly composed of cancer-associated fibroblasts (CAFs), vascular endothelial cells, lymphocytes and cells. CAFs, compared to normal fibroblasts, have a more evident proliferation capacity and play an important role in promoting tumor proliferation, invasion and metastasis. The research also discusses the importance of the Tumor-Stroma Ratio (TSR) and Tumor Infiltrating Lymphocytes (TILs) in the prognosis of breast cancer patients. Previous studies have shown that the prognosis of patients in the high stroma group was worse than that of the low stroma group in gastric, colon and triple-negative breast cancers . However, this study showed that the overall survival rate and the disease-free survival rate of patients with primary breast cancer in the low stromal group were significantly higher than those in the high stromal group. Conclusion: Our study shows that the positive correlation of TSR in primary and metastatic lymph node cancer can be used as an independent factor in the prognostic judgement of breast cancer. However, TSR in primary cancer has a much more prognosis-orientated significance. The combined analysis of TSR and TILs becomes very useful as a tool for determining prognosis and guiding the clinical treatment of breast cancer. Citation Format: Fiorita Mundim, Angela Logullo, Karine Infante, Joaquim Neto, Edson Barbosa, Paulo Maia, Nathalia Sousa, Pedro Mundim, Gil Facina. Combination of tumor-infiltrating lymphocytes (TILS) and tumor-stroma ratio (TSR) in breast cancer: utility to guide clinical treatment of breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-09-01.

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