Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer.

Ramadhan Karsono,Teguh Aryandono,Fahreza Saputra,Muhammad Azhar,Yulia Pratiwi,Siti Nadliroh

doi:10.31557/apjcp.2021.22.7.2069

Abstract

Objective:The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. Methods:Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. Results:Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019). Conclusion:Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.

Highlights

Breast cancer has a high incidence and mortality rate and is estimated to be the most common malignancy in females worldwide
Our study found that expression of Programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) in breast cancer patients is mostly increased after chemotherapy with 57.1%, 62.9% and 60% patients have an increase in PD-1, PD-L1, and PD-L2 expression, respectively (Table 2)
While 42.9%, 37.1%, and 40% breast cancer patients have their PD-1, PD-L1, and PD-L2 expression decreased after chemotherapy

Summary

Introduction

Breast cancer has a high incidence and mortality rate and is estimated to be the most common malignancy in females worldwide. Every year incidences of breast cancer increase by more than 5%. In developing countries including Indonesia, most breast cancers were detected in advanced stages (3 and 4). Death is higher in low development countries (Ghoncheh et al, 2016; Youlden et al, 2014; Yuan et al, 2019). Types of therapies commonly used to treat breast cancer are radiotherapy, surgery, chemotherapy, hormone therapy, and targeted therapy. These therapies are not effective enough to treat breast cancer (Zhang et al, 2017)

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Conclusion