Programmed Death-Ligand 1 (PD-L1) as Immunotherapy Biomarker in Breast Cancer

SIMPLE SUMMARY: Breast cancer (BC) is the most common malignant neoplasm in women and one of the leading causes of cancer death in women worldwide. Programmed death-ligand 1 (PD-L1) is becoming an emerging biomarker in BC in recent years. It has been correlated with worse outcomes in patients with hormone receptor positive, but it has a predictive role to guide response to systemic treatment in the triple-negative breast cancer (TNBC) subtype, especially in the metastatic setting. Immune checkpoint inhibitors are beginning to be a part of the treatment for many TNBC patients. However, more studies are needed in order to identify wherefore immunotherapy benefits TNBC patients regardless of PD-L1 status in the localized disease, but only offer an improvement for PD-L1 positivity expression in the advanced setting. The aim of this review is to analyze PD-L1 in all BC subtypes, including clinical trials with anti-PD-1/L1 and their results. ABSTRACT: Breast cancer constitutes the most common malignant neoplasm in women around the world. Approximately 12% of patients are diagnosed with metastatic stage, and between 5 and 30% of early or locally advanced BC patients will relapse, making it an incurable disease. PD-L1 ligation is an immune inhibitory molecule of the activation of T cells, playing a relevant role in numerous types of malignant tumors, including BC. The objective of the present review is to analyze the role of PD-L1 as a biomarker in the different BC subtypes, adding clinical trials with immune checkpoint inhibitors and their applicable results. Diverse trials using immunotherapy with anti-PD-1/PD-L1 in BC, as well as prospective or retrospective cohort studies about PD-L1 in BC, were included. Despite divergent results in the reviewed studies, PD-L1 seems to be correlated with worse prognosis in the hormone receptor positive subtype. Immune checkpoints inhibitors targeting the PD-1/PD-L1 axis have achieved great response rates in TNBC patients, especially in combination with chemotherapy, making immunotherapy a new treatment option in this scenario. However, the utility of PD-L1 as a predictive biomarker in the rest of BC subtypes remains unclear. In addition, predictive differences have been found in response to immunotherapy depending on the stage of the tumor disease. Therefore, a better understanding of tumor microenvironment, as well as identifying new potential biomarkers or combined index scores, is necessary in order to make a better selection of the subgroups of BC patients who will derive benefit from immune checkpoint inhibitors.