PD-L1 May Be a Future Target in Breast Cancer Treatment

Programmed cell death-ligand 1 (PD-L1) has emerged as an important target for immunotherapy in several types of cancer. In fact, researchers have found that PD-L1 is expressed in 20% to 70% of patients with lung cancer, urinary bladder cancer, malignant melanoma, or ovarian cancer.¹ As a result, anti‒PD-1 agents, such as pembrolizumab, and anti‒PD-L1 agents, such as durvalumab, have been developed to treat tumors expressing these biomarkers. Although results from several studies have suggested that patients with breast cancer have an immune response defect,¹ breast cancer has not traditionally been considered immunogenic in nature.

Researchers of a study recently published in BMC Cancer sought to determine the association between PD-L1 expression in breast cancer and clinicopathologic factors and outcomes.¹ This meta-analysis reviewed studies that met the following criteria: (1) evaluated the prognostic or clinicopathologic significance of PD-L1 expression in patients with breast cancer and reported ≥1 survival-related outcomes; (2) used an anti‒PD-L1 antibody for immunohistochemistry; and (3) obtained specimens via core needle biopsy or from the postoperative specimen. A total of 6 studies encompassing 7877 patient cases were included in the meta-analysis.

Kim and colleagues found that higher PD-L1 expression in all cells was associated with higher histologic grade and with lymph node metastasis. Additionally, higher PD-L1 expression in tumor cells was associated with larger tumor size, estrogen-receptor negativity, progesterone-receptor negativity, HER2 positivity, and triple-negative breast cancer.¹

Overall, the meta-analysis showed that “PD-L1 positivity in all cells was associated with poorer DFS [disease-free survival], compared to PD-L1 negativity, although there was no significant difference in OS [overall survival].” 

A separate study of 5454 breast cancer cases supports these results. Sabatier and colleagues found that “PD-L1‒positive cells are more invasive and have an aggressive phenotype, compared to other cells,” which suggests that PD-L1 positivity may be associated with poorer overall survival.²

Since PD-L1 expression in all cells of patients with breast cancer is associated with poorer DFS, in the future, PD-L1 quantification may help determine whether anti‒PD-L1 therapy is appropriate in patients with an elevated PD-L1 phenotype.
 
References

1. Kim HM, Lee J, Koo J. Clinicopathological and prognostic significance of programmed death ligand-1 expression in breast cancer: a meta-analysis. BMC Cancer. 2017;17:690-700.

2. Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015;6:5449-5464.