Abstract PS5-27: The predictive value of tumor-infiltrating lymphocytes and PD-L1 expression on the efficacy of neoadjuvant trastuzumab plus chemotherapy in HER2-positive breast cancer
Authors: Li Huihui , Shang Mao , Chi Yajing , Yin Sha 
Published: February 2021

Background:Many studies have explored the predictive factors for the efficacy of neoadjuvant therapy in HER2 + breast cancer. However, no reliable and widely used biomarker was found till now except several clinicalpathologic factors including HER2. HER2 oncogene can regulate the recruitment and activation of tumor-infiltrating immune cells (TILs) and trastuzumab therapeutic effects by inducing programmed death ligand 1 (PD-L1), suggesting that TILs and the expression of PD-L1 may be associated with the efficacy of trastuzumab. Several studies have verified certain predictive value of TILs and PD-L1 in HER2 + breast cancer patients, but controversy remains. Besides, most of them focus on the expression of PD-L1 or TILs before neoadjuvant therapy, but not the change in the paired tissues before and after neoadjuvant therapy. This study aimed to investigate the change of TILs and the expression of PD-L1 in the paired tissues before and after neoadjuvant therapy and the correlation to the efficacy of neoadjuvant trastuzumab plus chemotherapy and disease-free survival (DFS) in HER2+ breast cancer patients.Methods:HER2+ breast cancer cases receiving neoadjuvant therapy (n=115) were retrospectively collected between July 2013 and November 2018. The expression of PD-L1 was detected by immunohistochemistry using SP142 antibody and the percentage of positive membranous staining in tumor cells (TC-PD-L1) and TILs (TILs-PD-L1) was scored respectively. TIL percentile score for full sections were assessed by two pathologists independently. Results:In our study, 87 patients receiving neoadjuvant chemotherapy alone, and 68 patients receiving neoadjuvant trastuzumab plus chemotherapy. Among them, 39 patients achieved pCR and 116 patients were non-pCR. Univariate analysis confirmed that the pCR was positively correlated with high TILs and TILs-PD-L1 expression before neoadjuvant therapy (P&lt; 0.05). Multivariate logistic regression analysis confirmed that pre-treatment TILs-PD-L1 expression but no other clinicalpathologic factors,was independent predictor of pCR in neoadjuvant therapy (P&lt;0.05).Among all patients, TILs increased in breast cancer tissues after neoadjuvant therapy (P&lt;0.001). Consistent results were found in subgroup analysis of trastuzumab plus chemotherapy group and chemotherapy alone group (P&lt;0.05). In 116 non-pCR patients, TC-PD-L1 was down-regulated in breast cancer tissues after neoadjuvant therapy (P=0.0219). Consistent results were found in 43 non-pCR patients receiving neoadjuvant trastuzumab plus chemotherapy(P=0.0437). While in 73 non-pCR patients receiving neoadjuvant chemotherapy, there was no significant difference in TC-PD-L1 expression before and after neoadjuvant therapy (P=0.1465). On the other hand, in the general population, neoadjuvant trastuzumab plus chemotherapy group and neoadjuvant chemotherapy group, TILs-PD-L1 were all down-regulated after treatment(P&lt;0.05).Kaplan-Meier analysis showed that the changes of TILs, TC-PD-L1, TILs-PD-L1 between pre and post neoadjuvant therapy have no correlations with DFS. In multivariate Cox regression analysis, lymph node status and distant metastasis were independent prognostic factors for DFS.Conclusions:1. Pre-treatment high TILs-PD-L1 was an independent predictor of PCR in patients with HER2+ breast cancer treated with neoadjuvant therapy.2. Trastuzumab maybe relate to the down-regulation of TC-PD-L1 and TILs-PD-L1 expression. 3. Lymph node status and distant metastasis were independent prognostic factors.4. Both TILs-PD-L1 and TILs change before and after neoadjuvant therapy for HER2-positive breast cancer, which may suggest that the immune microenvironment plays a role in neoadjuvant therapy.

Citation Format: Huihui Li, Mao Shang, Yajing Chi, Sha Yin. The predictive value of tumor-infiltrating lymphocytes and PD-L1 expression on the efficacy of neoadjuvant trastuzumab plus chemotherapy in HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-27.