Discrepancy of PD1/ PD-L1 status between primary and metastatic triple negative breast cancer in diagnostic biopsies

Abstract

Introduction

The evaluation of programmed death protein-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) has become routine for accurate decisions regarding immune checkpoint therapy. The aim of our paper was to analyze whether the PD-L1 evaluated in biopsy specimens accurately reflects its expression in the whole tumor and paired metastases in TNBC.

Methods

Immunohistochemistry was applied on 66 biopsy and resection specimens from TNBC cases and matched metastasis to determine PD-L1 status. PD-L1 was evaluated using 4 scoring methods immune cell (IC) and tumor cell (TC) with a 1% as the cutoff value, and combined positive scores (CPSs) with a 1% and 10% as the cutoff value.

Results

A total of 66 TNBC patients show a statistically significant PDL1 IC positive expression with unfavorable prognostic factors. PD-L1 was positive in IC more than TC in biopsy specimen and in surgical specimen. The overall concordance between biopsies and surgical specimens at IC score was 55.2%, at CPS 1% it was 65.2%, and at CPS 10 it was 68.2%. The pooled discordance rate varied according to the cells that expressed PD-L1: A total of 37.9% of cases had discordant primary/metastatic PD-L1 status when it was assessed on immune cells, 31.8% when it was assessed on tumor cells, and 28.8% when it was assessed by CPS > 10%

Conclusions

Misclassifying TNBC patients as PD-L1-negative at biopsy can lead to disqualification from anti-PD-L1 therapy. PD-L1 status conversion occurs frequently between primary tumor and metastases, emphasizing the need for multiple biopsies, adequate tissue sampling, additional tests, and standardization in immunotherapy selection.