Abstract P2-04-20: PD-L1 expression in triple negative breast cancer (TNBC) is associated with improved outcomes
Authors: Mardones MA , Grosser D , Levin MK , Daoud Y , Palucka K , O'Shaughnessy J , Osborne C 
Published: March 2017

Background: Breast cancer (BC) evolution is influenced by tumor microenvironment. Presence of CD8+ cytotoxic T lymphocytes (TILs) has been proposed as surrogate marker of adaptive immune response, and programmed death ligand-1 (PD-L1) is a negative regulator of the tumor immune microenvironment. However, whether PD-L1 expression adversely affects breast cancer outcome is unknown (Oncotarget 2014; 6:5449). Tumor-associated macrophages (TAMs) in the tumor microenvironment may contribute to BC progression and metastagenicity. We assessed the potential correlations between PD-L1 expression, the presence of TAMs and TILs, and BC outcomes.

Methods: 59 primary BCs (16 HR+, 16 HER2+, and 27 TNBC) with known clinical and pathological features and patient (pt) follow-up for a median of 3.9 years were evaluated by immunohistochemistry for expression of CD8, CD68, and PD-L1 within tumor and stroma. The average number of CD8+ cells within 10 high power fields was determined separately for invasive tumor cell nests and for stroma within each sample, and the median number of CD8+ cells within tumor vs stroma was calculated (Breast Cancer Res Treat 2011 128:703–711). Non-lymphocyte mononuclear cells in tumor and stroma were used in counting CD68+ TAMs. BCs were positive for CD8+ TILs (Cell Marque clone #C8144B) or CD68+ TAMs (Cell Marque clone #KP1) if the number of cells positive in the sample was greater than the median. PD-L1 (Dako 28-8 pharmDx) was positive if at least 1% of tumor cells expressed PD-L1. The log-rank was used to compare the survival and progression free survival between groups and Spearman's rank-order correlation tests were conducted to determine associations between CD8, CD68, and PD-L1.

Results: 57% of TN, 26% of HER2+ and 13% of HR+ BCs expressed PD-L1 in tumor. TNBC pts received anthracycline/ taxane chemotherapy (62%) or taxane therapy alone (22%). HR+ and HER2+ pts received standard endocrine therapy and trastuzumab-based therapy. Stromal CD8+ TILs were associated with improved OS in the overall population (log rank p=0.026). In TNBC, PD-L1 expression was positively correlated with the presence of TILs (p=0.0002) and TAMs (p=0.0005) as well as with improved 3 year PFS and OS (log rank p=0.04 and p=0.03, respectively). Furthermore, stromal CD8+ TILs and stromal CD68+ TAMs correlated positively with each other in the TNBC group (p=0.0094).

Conclusions: PD-L1 expression correlated with TILs and TAMs in TNBC and was associated with a favorable outcome. PD-L1+ TNBCs with high levels of TILs and TAMs may be primed for exceptional response to immunogenic chemotherapy alone. Whether some pts with PD-L1+ TNBCs with high TILs/TAMs will benefit additionally from an anti-PD-L1/PD-1 agent is being investigated currently.

Citation Format: Mardones MA, Grosser D, Levin MK, Daoud Y, Palucka K, O'Shaughnessy J, Osborne C. PD-L1 expression in triple negative breast cancer (TNBC) is associated with improved outcomes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-20.