Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
Rustamadji P., Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Hospital, Jakarta, Indonesia; Wiyarta E., Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Hospital, Jakarta, Indonesia; Pramono M., Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Hospital, Jakarta, Indonesia; Maulanisa S.C., Department of Anatomic Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
Background: Response to neoadjuvant chemotherapy (NC) in individuals with invasive breast cancer (IBC) must be monitored, and biomarkers are needed. NC can activate an anti-tumour immune response in its microenvironment, known as Tumor-infiltrating Lymphocytes (TIL). TIL components believed to have great potential as predictors are CD4+, CD8+, and FOXP3+ TIL. This study aims to explore TIL components that can potentially be predictive biomarkers of NC pathological responses. Methods: A sample size of 40 were analyzed based on the relationship between CD4+, CD8+, and FOXP3+ TIL expression with the Miller-Payne (MP) grading system. Age, tumour grade, PR, ER, Ki-67, and HER2 were also evaluated. CD4+, CD8+, and FOXP3+ TIL expressions were analayzed by IHC staining, while other data were collected from archives. Data was analyzed using univariate and multivariate analysis. Results: Univariate analysis showed a significant relationship between CD4+ TIL and MP (p<0.001), CD8+ and MP (p=0.004), and FOXP3 with MP (p<0.001). The simultaneous integration of the three biomarkers in one model was not good enough to be a predictive model. Therefore, an exploratory analysis was conducted by testing several alternative models that combined two of the three existing biomarkers. It turned out that CD4+ TIL in model 2 (CD4+CD8+) and FOXP3+ TIL in model 4 (CD8+FOXP3+) showed significant coefficient values. Moreover, all of the threshold coefficients in model 4 are significant. Conclusion: This study shows that CD4+, CD8+, and FOXP3+ TIL have promising potential as predictive biomarkers. In particular, FOXP3+ is dominant in predictive models of pathological response in patients with IBC. This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.
National Agency for Research and Innovation via Publikasi Terindeks Internasional; Universitas Indonesia, UI; PUTI; Ministry of Research; Agencia Nacional de Investigación e Innovación, ANII; Direktorat Riset and Pengembangan, Universitas Indonesia, DRPM UI; Publikasi Terindeks Internasional, (NKB-193/UN2, RST/HKP.05.00/2022)
Funding text 1: This work was supported by grants from the Directorate of Research & Development Universitas Indonesia and the Ministry of Research/National Agency for Research and Innovation via Publikasi Terindeks Internasional (PUTI) Pascasarjana Q3 grant number NKB-193/UN2. RST/HKP.05.00/2022.; Funding text 2: Universitas Indonesia and the Ministry of Research/ National Agency for Research and