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. 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.

Automated summary

This article examines the role of PD-L1 as a biomarker in different subtypes of breast cancer, including clinical trials with immune checkpoint inhibitors and their results. PD-L1 appears to be associated with worse prognosis in the hormone receptor positive subtype. In triple-negative breast cancer patients, immune checkpoint inhibitors have shown good treatment response, especially when combined with chemotherapy. However, the utility of PD-L1 as a predictive biomarker in other breast cancer subtypes remains unclear.