Tumor Immune Microenvironment and Response to Neoadjuvant Chemotherapy in Hormone Receptor/HER2+Early Stage Breast Cancer

• Type of Material: Article
• Authors: Rami S Vanguri, Memorial Sloan Kettering Cancer Center, New York; Kathleen M Fenn, Columbia University; Matthew R Kearney, Columbia University; Qi Wang, Columbia University; Hua Guo, Columbia University; Douglas K Marks, NYU Langone Health; Christine Chin, Columbia University; Claire F Alcus, Columbia University; Julia B Thompson, Columbia University; Cheng-Shiun Leu, Columbia University; Hanina Hibshoosh, Columbia University; Kevin M Kalinsky, Emory University; James C Mathews, Memorial Sloan Kettering Cancer Center, New York; Saad Nadeem, Memorial Sloan Kettering Cancer Center, New York; Travis J Hollmann, Memorial Sloan Kettering Cancer Center, New York; Eileen P Connolly, Columbia University
• Language: English
• Date: 2022-07-25
• Publisher: CIG MEDIA GROUP, LP
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.clbc.2022.04.002
• Title of Journal or Parent Work: CLINICAL BREAST CANCER
• Volume: 22
• Issue: 6
• Start Page: 538
• End Page: 546
• Grant/Funding Information: This work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number KL2 TR000081.
• Keywords: Oncology; SAFETY; Gene expression signatures; PLUS TRASTUZUMAB; INFILTRATING LYMPHOCYTES; Science & Technology; LAPATINIB; Quantitative multiplex immunofluorescence; Life Sciences & Biomedicine; HER2 positive; Tumor infiltrating lymphocytes; PATHOLOGICAL COMPLETE RESPONSE; SURVIVAL; PERTUZUMAB; COMBINATION; NEOSPHERE; Breast cancer
• Research Categories: Engineering, Biomedical; Health Sciences, Oncology; Health Sciences, Pathology; Biophysics, Medical; Health Sciences, Public Health; Biology, Biostatistics

Abstract

Background: Pathologic response at the time of surgery after neoadjuvant therapy for HER2 positive early breast cancer impacts both prognosis and subsequent adjuvant therapy. Comprehensive descriptions of the tumor microenvironment (TME) in patients with HER2 positive early breast cancer is not well described. We utilized standard stromal pathologist-assessed tumor infiltrating lymphocyte (TIL) quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting. Methods: We utilized standard stromal pathologist-assessed TIL quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in 28 patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting. Results: Pathologist-assessed stromal TILs were significantly associated with pathologic complete response (pCR). By quantitative multiplex immunofluorescence, univariate analysis revealed significant increases in CD3+, CD3+CD8-FOXP3-, CD8+ and FOXP3+ T-cell densities as well as increased immune cell aggregates in pCR patients. In subsets of paired pre/post-treatment samples, we observed significant changes in gene expression signatures in non-pCR patients and significant decreases in CD8+ densities after treatment in pCR patients. No RNA based pathway signature was associated with pCR. Conclusion: TME characterization HER2 positive breast cancer patients revealed several stromal T-cell densities and immune cell aggregates associated with pCR. These results demonstrate the feasibility of these novel methods in TME evaluation and contribute to ongoing investigations of the TME in HER2+ early breast cancer to identify robust biomarkers to best identify patients eligible for systemic de-escalation strategies.