Jing Zhao1, Jane Meisel2, Yi Guo3, Rita Nahta4, Kung Lin Hsieh5, Limin Peng3, Zhimin Wei1, Ruth O'Regan6, Xiaoxian Li7. 1. Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China. 2. Department of Hematology and Oncology, Emory University, Atlanta, GA, USA. 3. Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA. 4. Department of Pharmacology, Emory University, Atlanta, GA, USA. 5. Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA. 6. Department of Medicine, University of Wisconsin, Madison, WI, USA. 7. Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA. xli40@emory.edu.
Abstract
BACKGROUND: The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy. METHODS: We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate. RESULTS: Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096). CONCLUSIONS: High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.
BACKGROUND: The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy. METHODS: We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate. RESULTS: Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096). CONCLUSIONS: High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.
Entities:
Keywords:
CD8; FOXP3; HER2+ breast cancer; HER2-targeted therapy; Neoadjuvant therapy; PD-L1; Predictive; Response; TIL
Authors: Hongxiao Li; Jigang Wang; Zaibo Li; Melad Dababneh; Fusheng Wang; Peng Zhao; Geoffrey H Smith; George Teodoro; Meijie Li; Jun Kong; Xiaoxian Li Journal: Front Med (Lausanne) Date: 2022-06-14
Authors: Mostafa M Saber; Heba M El Zawahry; Amany M Hilal; Amany A Abou-Bakr; Alfred E Namour; Mona M Saber Journal: Asian Pac J Cancer Prev Date: 2022-02-01