Abstract P2-10-02: PD-L1 protein expression is a prognostic biomarker in breast cancer

Abstract

Abstract BACKGROUND: Programmed death ligand 1 (PD-L1) and its receptor, PD1, are involved in limiting immune response. In the context of cancer, tumor cells expressing PD-L1 can suppress the immune response of PD1-expressing tumor infiltrating lymphocytes (TILs). Disruption of this pathway with antibodies to either the ligand or the receptor has shown promise in the treatment of non small cell lung cancer, melanoma and renal cell cancer. Here we investigate the pathway in breast cancer. METHODS: PD-L1 protein expression was assessed on two Yale TMA breast cancer cohorts with two-fold redundancy by quantitative immunofluorescence (QIF) using AQUA technology. Cohort 1 (YTMA201) consists of 400 patients with has extensive follow-up and adjuvant treatment information. Cohort 2 (YTMA128) consists of 245 patients with limited follow-up and no treatment information. The PD-L1 antibody (Lieping Chen, clone 5H1) has been previously validated for specificity and reproducibility using transfected cell models. TILs were assessed by a pathologist for each cohort using a score from 0-3 based on the amount of TILs within the spot. AQUA scores for PD-L1 were used as a continuous variable and also cut at the median for outcome analysis. RESULTS: PD-L1 protein is positively correlated with TILs (p<0.0001 on cohort 1 and p = 0.0072 on cohort 2) and inversely correlated with estrogen receptor status (p<0.0001 on cohort 1 and p = 0.0188 on cohort 2) on both breast cancer cohorts examined (total n = 594). On cohort 1, PD-L1 protein expression is a marker of good prognosis as a continuous variable (p = 0.0271) as well as when cut at the median (p = 0.0151), particularly in the estrogen receptor positive subset of patients. CONCLUSIONS: PD-L1 expression in breast cancer is positively associated with TILs and inversely associated with estrogen receptor status on two independent breast cancer cohorts. PD-L1 protein expression shows prognostic value in breast cancer patients, particularly the ER positive subset of patients. Further assessment of PD-1 axis marker expression may be valuable as the associated therapeutics are being tested in breast cancer patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-10-02.