Hubungan Sel Myeloid-Derived Supressor, T Regulatori dan Carcinoma Associated Fibroblast dengan Grade Histopatologi Penderita Kanker Payudara Tripel Negatif Usia Muda sebagai Faktor Prediktor Keberhasilan Kemoterapi

Abstract

Background: Breast cancer is a heterogeneous type of cancer due to variations in clinical picture, tumor biology behavior and response to chemotherapy. Patients with breast cancer at a young age are often associated with a poor prognosis, often found in triple negative subtypes, high histological grades and lymph node involvement. The tumor consists of cancer cells and stroma in the form of vascularization, fibroblasts (Carcinoma Associated Fibroblasts/CAF) and infiltrating immune cells which will then form a tumor-microenvironment. This formation will make it easier for tumors to grow, metastasize and avoid immune-mediated destruction. Patients with triple negative subtypes often experience treatment failure. It is necessary to develop the provision of additional therapy that is adjusted to the patient's immune condition to increase the success of therapy and the patient's life expectancy and prevent resistance to treatment. Objective: To analyze the relationship between myeloid derived suppressor cells, Tregulatori and carcinoma associated fibroblasts with histopathological grades in young triple negative breast cancer patients as predictors of chemotherapy respon. Methods: This is an analytic study with a retrospective cohort design, conducted in paraffin blocks in 45 breast cancer patients aged ≤ 40 years at the time of diagnosis. Data collection from medical records for 2018-2021 included invasive breast cancer NOS type, histopathological grade, triple negative subtype and had never received chemotherapy before. CD11b, Foxp3 and Vimentin immunohistochemical examination was performed to analyze expression in MDSC, Treg and CAF cells. Immunoexpression of these cells was analyzed using ImageJ Analysis. After the patient received neoadjuvant chemotherapy, a mastectomy was performed, then the regression of the tumor cells was examined using Miller-Payne scoring. Results: In this study the average age of the patients was 38.4 years (the youngest was 29 years old, the oldest was 40 years, grade 3 was 82.22%, metastases to the KGB were 60% and the most tumor size was T3 (> 5 cm) of 37 .78%.The highest Miller- Payne score was on score III (64.4%), none of the patients had a complete response.The immunohistochemical examination showed that the expression of MDSC cells correlated with histopathological grade, tumor size and LVI (p<0.01 While Treg cell expression was associated with histopathological grade (p<0.01), the intensity of Vimentin showed a more intense color associated with histopathological grade (p<0.01), tumor size and LVI (p<0.05). Whereas the response to neoadjuvant chemotherapy (docetaxel and platinum base) does not have a Miller-Payne scoring relationship, but has a tendency for low grades to show more partial responses. Conclusion: This study shows that MDSC, Treg and Carcinoma associated fibroblast cells are associated with histopathological grade, but did not show a relationship with the success of conventional neoadjuvant chemotherapy. Additional therapy targeting MDSC, Treg and anti-vimentin should be given to increase the success of therapy.