• Jing Zhao, Jane Meisel, Yi Guo, Rita Nahta, Kung Lin Hsieh, Limin Peng, Zhimin Wei, Ruth O'Regan, and Xiaoxian Li.
• Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
• Breast Cancer Res. Treat. 2020 Oct 1; 183 (3): 599-606.

BackgroundThe 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.MethodsWe 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.ResultsUnivariate 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).ConclusionsHigh 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.

22 keywords...

hide…