Abstract P3-07-37: Quantitative analysis of T cell and macrophage immune markers in Her2-positive breast cancer
Authors: SL Shiao, A Gertych, Z Ma, X Zhang, CM Burnison, AJ Mirhadi, A Giuliano, BS Knudsen, A Chung
Journal: Cancer Research (2016)

Abstract Purpose/Objectives: Her2-neu positive breast cancers have a good overall prognosis with the advent of Her2-directed therapies such as trastuzumab. However, despite the increased efficacy with Her-2-directed therapies 20-30% of patients still have local and/or distant failure despite being Her-2 amplified on pathology. The etiology of this local failure remains unknown. Recent evidence has suggested that there may be immune factors that contribute to the progression of breast cancer and the response to therapy so we undertook a study to examine the relationship between immune-based markers and traditional pathologic and clinical markers of outcome. Materials/Methods: Paraffin-embedded sections were generation and clinical records were reviewed for 88 patients, age ≥ 18 years, with pathologically-proven Her2-neu+ breast cancer who were treated at a single institution from 01/2001 to 12/2013. Single-color immunohistochemical staining was performed for CK5/6, CK14 and EGFR and scored by a breast pathologist. Adjacent sections were also then stained for CD45, CD4, CD8 and CD68 using a multi-color immunohistochemical approach. Slides were scanned using the Vectra Automated Quantitative Pathology Imaging System and analyzed using an in-house algorithm to quantitate the number of immune cells within the tumor, tumor margin and within 2 mm outside the tumor. We then compared the level of CK5/6, CK14, EGFR with the number of immune cells. The number of different immune cells were also analyzed with respect to other clinical parameters including age, tumor size, nodal status, hormone receptor status, time to progression, progression-free survival and overall survival. Results: At a median follow-up of 66.5 months, 20 (22.7%) patients had progressed. We found that the number of CD45+ leukocytes at the margin correlates with the expression of CK5/6 (p = 0.015) which predicted for local failure. Further, we found that the ratio of CD8 to CD4 cells within the tumor and margin highly correlates with the expression of the hormone receptors (p = 0.01). Conclusions: Our preliminary results suggest that immune markers may be important predictors of a basal-like phenotype as defined by CK5/6 expression in Her2+ breast cancers which itself correlated with significantly higher local failure. Further higher CD8 to CD4 ratios were highly correlated with hormone receptor expression, particularly PR expression suggesting that in the Her2+ population the more favorable prognosis for the "triple-positive" subtype of Her2+ cancers may be in part due to a more favorable immune microenvironment. Citation Format: Shiao SL, Gertych A, Ma Z, Zhang X, Burnison CM, Mirhadi AJ, Giuliano A, Knudsen BS, Chung A. Quantitative analysis of T cell and macrophage immune markers in Her2-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-37.