Abstract P4-10-30: PD-L1 expression in tumor infiltrating lymphocytes (TILs) inversely correlates with androgen receptor (AR) expression in HER2-positive breast cancer
Authors: Shen Tiansheng , Pincus Jennifer L. , Siziopikou Kalliopi P. 
Published: March 2020

Abstract
Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for 20-30% of breast carcinomas and is associated with a poor prognosis. While anti-HER2 targeted therapies have improved outcomes within this group, a subset of these tumors eventually develop resistance urgently requiring novel therapeutic options. In addition to classic HER2+ subtype, estrogen receptor (ER)-positive and HER2-positive tumors (luminal B) are another subtype of HER2 expressing breast carcinomas which could also benefit from additional therapies. Targeting the androgen receptor (AR) pathway and the PD-L1 axis may represent potential new therapeutic strategies in breast cancer. Our group previously reported that AR expression is seen in ¾ of HER2+ carcinomas and is more common in luminal B compared to classic HER2+ tumors. In this report, we evaluated expression of PD-L1 in tumor infiltrating lymphocytes (TILs) in both classic HER2 + and Luminal B subtypes of breast carcinomas and correlated the expression of PD-L1 with AR expression in these tumors. Methods: The study population consisted of 114 patients with HER2-positive invasive breast carcinoma diagnosed from 2009-2014 at Northwestern Memorial Hospital. Electronic medical records were reviewed for patient demographics (mean age 54, range 23-80). Pathologic tumor characteristics (histologic type, size, and grade) and tumor marker profile (ER and HER2) were evaluated. Tissue microarrays were constructed (3 cores from each case to account for tumor heterogeneity) for immunohistochemical evaluation of AR and PD-L1. AR was graded as positive when at least 1% of tumor cells showed nuclear immunoreactivity. For PD-L1, the extent of staining (0%=0, 1-10%=1, 11-50%=2, and 51-100%=3) and staining intensity (0, 1+, 2+, 3+) were assessed in TILs. Then a composite score (CS) was calculated by multiplying extent and intensity results (range 0-9; 0-3=negative, 4-9=positive). Results: Of the 114 studied breast carcinoma cases, 54 were classic HER2+ tumors (47%) and 60 were luminal B (53%) tumors. Approximately 69% of classic HER2+ and 87% of luminal B cases were positive for AR. Of interest, in classic HER2+ cases, the expression of PD-L1 in TILs was inversely correlated with the expression of AR, with 82% (14/17) of AR- tumors being positive for PD-L1 in TILs compared to only 46% (17/37) of AR+ tumors with PD-L1 expression in TILs (p&lt;0.01). No association of expression of PD-L1 in TILs with AR expression was observed in luminal B cases (62% in AR+ versus 50% in AR- tumors; p=0.70). Moreover, in classic HER2+/AR- group, grade 3 tumors were seen almost exclusively in the PD-L1 expressing group (13 versus 3), in contrast to the equal number of grade 3 tumors in classic HER2+/AR+ group regardless of PD-L1 expression in TILs (14 versus 14). No association of the PD-L1 expression with age, race, and tumor histologic types was observed in classic HER2+/AR+ or classic HER2+/AR- cases. Conclusions: Our results demonstrated that the expression of PD-L1 in TILs was inversely correlated with the expression of AR in classic HER2 positive tumors but not in luminal B tumors. We also found that in classic HER2+/AR- group, grade 3 tumors were seen almost exclusively in the PD-L1 expression group. Our findings add to the body of knowledge of the molecular mechanisms that drive the different molecular subtypes of breast carcinomas and raise the interesting possibility that new treatment strategies such as targeting the PD-L1 axis may show more benefit against the AR negative subtype of the classic HER2 positive carcinomas.
Citation Format: Tiansheng Shen, Jennifer L. Pincus, Kalliopi P. Siziopikou. PD-L1 expression in tumor infiltrating lymphocytes (TILs) inversely correlates with androgen receptor (AR) expression in HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-30.