Faculty Collaboration Database

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer. JCO Precis Oncol 2023 Jan;7:e2100498

Date

01/19/2023

Pubmed ID

36652667

Pubmed Central ID

PMC9928763

DOI

10.1200/PO.21.00498

Abstract

PURPOSE: T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer.

METHODS: PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors.

RESULTS: Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001).

CONCLUSION: Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.

Author List

Chervoneva I, Peck AR, Sun Y, Yi M, Udhane SS, Langenheim JF, Girondo MA, Jorns JM, Chaudhary LN, Kamaraju S, Bergom C, Flister MJ, Hooke JA, Kovatich AJ, Shriver CD, Hu H, Palazzo JP, Bibbo M, Hyslop T, Nevalainen MT, Pestell RG, Fuchs SY, Mitchell EP, Rui H

Authors

Lubna N. Chaudhary MD Associate Professor in the Medicine department at Medical College of Wisconsin
Julie M. Jorns MD Professor in the Pathology department at Medical College of Wisconsin
Sailaja Kamaraju MD Associate Professor in the Medicine department at Medical College of Wisconsin
Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

B7-H1 Antigen
Humans
Programmed Cell Death 1 Receptor
Retrospective Studies
Triple Negative Breast Neoplasms