Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients

Abstract

Purpose: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients.

Methods: Tumor-infiltrating lymphocytes (TILs) and CD20⁺ B-cell frequencies (CD20⁺), and PD-L1 expression on tumor (PD-L1⁺carcinoma cells) and immune (PD-L1⁺TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models.

Results: IBC and LABC display similar levels of TILs, CD20⁺, and combined CD20⁺ and PD-L1⁺TILs (CD20⁺PD-L1⁺TILs), while LABC contained more PD-L1⁺TILs and PD-L1⁺ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1⁺ carcinoma cells, and combined CD20⁺ and PD-L1⁺ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1⁺TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20⁺ and CD20⁺PD-L1⁺TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20⁺PD-L1⁺TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC.

Conclusion: CD20⁺PD-L1⁺TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.

Keywords: CD20; Immuno-oncology; Inflammatory breast cancer; Locally advanced breast cancer; PD-L1; Patient outcomes; Tumor-infiltrating lymphocytes; pCR.