Programmed Death-Ligand 1 Immunoexpression in Triple Negative Breast Carcinoma in South Indian Women: A Cross-sectional Study at a Tertiary Care Centre

Introduction: Triple Negative Breast Cancer (TNBC) comprises 10-20% of all breast cancer cases and is characterised by a lack of differentiation, subpar response to therapy and a low survival rate. Programmed Death-Ligand 1 (PD-L1) is a type 1 transmembrane protein present in cancer cells. The interaction between PD-1 (present on immune T cells) and PD-L1 facilitates negative immunoregulation, allowing cancer cells to elude the body’s immune system, resulting in tumour proliferation. This immune “brake” system translates to the presence of PD-L1 being associated with a poor prognosis and has been linked to low overall survival. Immune checkpoint inhibitors, which are immunomodulatory chemotherapeutic drugs, have the potential to disrupt this interaction and enable Immune Cells (IC) to attack Tumour Cells (TC). Aim: To analyse the immunohistochemical (IHC) expression of PD-L1 in TNBC patients and examine its association with clinicopathological prognostic variables such as patient age, laterality of the lesion, histopathological type, grade of the tumour, tumour size, lymphovascular invasion, perineural invasion, lymph node involvement, Ki-67 labelling index and tumour stage. Materials and Methods: This retrospective, cross-sectional study was conducted on 30 cases of modified radical mastectomy specimens from treatment-naïve TNBC patients, received in the Department of Pathology at Ramaiah Medical College, Bengaluru, Karnataka, India from January 2014 to January 2023. Data such as age, sex, tumour size, histological type, histologic grade, lymph node status and hormonal receptor status were collected. Haematoxylin and Eosin (H&E) slides were reviewed and sections containing the highest proportion of viable TCs with surrounding normal breast tissue and IC interface were chosen. IHC detection of PD-L1 was performed on 4-5 μm thick sections of the tumour. The PD-L1 scores of tumour and ICs were determined and the proportions of positive and negative cases were analysed with various clinicopathological variables. Results: Among the 30 TNBC cases studied for PD-L1 immunoexpression, 70% of the cases (21/30) showed a positive TC score (>1%) and a combined positive score (TC+IC) >1%. IC positivity was observed in 73.33% (22/30) of the cases. A higher histological grade (grade 3) and a patient age older than 50 years were significantly associated with positive TC scores (p-value=0.043), IC scores (p-value=0.049), and combined positive scores in this study. Conclusion: This study highlights the significant presence of PD-L1 immune expression in TNBC, paving the way for its potential use as a promising marker for identifying patients suitable for targeted immunotherapy in the TNBC phenotype. Future studies are expected to harmonise clone selection and scoring criteria, enabling the development of companion diagnostic kits specifically relevant to TNBC.