Clinical, histopathological, and immunological profiles of luminal invasive breast carcinoma in different stages

Keywords

breast cancer - tumor microenvironment - immune checkpoints - tumor-infiltrating lymphocytes

Breast cancer (BC) remains the most common type of cancer among women. Disease control must implement strategies that improve screening and predictive factors for response. Over recent years, several therapies have emerged in BC; however, many patients still do not respond, probability due to BC's heterogeneity, involving genetic, immune, and environmental factors. Thus, characterizing the components involved in the tumor microenvironment can provide insights to improve available therapies and identify potential predictive targets for treatment. Our goal was to evaluate clinical, pathological, and immunological profiles of invasive luminal BC in patients at various stages before treatment. In this study, 32 patients were recruited between 2017 and 2022, and initial (I+II, n = 15) and advanced (III+IV, n = 17) tumor stages were compared. Hematoxylin and eosin slides were analyzed to determine low, intermediate, or high tumor-infiltrating lymphocyte (TIL) percentages. Paraffin block sections from surgical or core biopsies were subjected to immunohistochemistry for CD8+, CD4+, CD68+, PD-1+, PD-L1+, and PD-L2+ immune markers. High expression of estrogen and progesterone receptors was associated with I+II stages. Additionally, higher expression of TILs was associated with a worse prognosis and was present in more advanced and aggressive tumors. Survival analysis showed better survival in initial-stage tumors (p = 0.06; 95% CI 0.02-1.10). Advanced-stage patients exhibited higher numbers of CD8+, CD4+, CD68+, PD-1+, PD-L1+, and PD-L2+ immune cells (p < 0.001) compared to initial tumor stages. Furthermore, the number of CD8+ and CD4+ TILs was positively correlated with CD68+, PD-1+, PD-L1+, and PD-L2+ immune cells. Nevertheless, CD68+ did not correlate with these immune checkpoints, indicating an altered immune response between initial and advanced tumor stages. TILs are recognized as predictive and prognostic factors for chemotherapy across various BC molecular subtypes; however, their role in luminal subtypes remains controversial. Therefore, accurately characterizing TILs is essential for clinical practice.

Corresponding author: Patrícia Rocha Martins (e-mail: [e-mail]).