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Abstract Objective: Breast Cancer is one of the most common malignant tumors in women. HER-2 is a driver gene for poor prognosis in breast cancer. Anti-HER-2 drugs have significantly improved the prognosis of patients with HER-2 positive metastatic breast cancer. There is still a lack of exploration of first-line anti-HER2 treatment options and translational studies only for patients with metastases after adjuvant and/or neoadjuvant trastuzumab therapy. This study is based on our previous clinical trial of pyrotinib in combination with albumin-bound paclitaxel in first line for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy, with the aim of exploring the efficacy and adverse events in the enrolled patients. And to explore the markers associated with Progression Free Survival (PFS) by using Olink technique to detect blood samples from patients. To provide a better screening of the benefit population and provide guidance for the treatment of HER-2 positive metastatic breast cancer. Methods: From December 2019 to July 2023, our previous clinical trial prospectively enrolls 27 patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. Pyrotinib (400 mg, po, qd) combined with albumin-bound paclitaxel (200 mg, ivdrip, d1, d8, q21d) was used as the first-line treatment regimen. Patients were evaluated for efficacy. Survival analysis was performed by using the Kaplan-Meier method. Blood samples were collected during treatment. We selected 21 blood samples from patients, and dynamically detected plasma protein changes by Olink technique. Differential protein analysis between groups according to hormone receptor status, trastuzumab primary/secondary resistance, and the presence of visceral metastases. And the proteins associated with PFS were analyzed. Results: Among the 27 patients whose efficacy had been evaluated, 7 patients were evaluated as CR, 18 patients as PR, and 2 patients as SD. The objective response rate was 92.6%, and the disease control rate was 100%. The median follow-up was 17.8 months and the median PFS has not yet been reached. Diarrhea is the most common adverse event. Grade 3 or higher adverse events include diarrhea, leukocytopenia, neutropenia, and hand-foot syndrome. The progression free survival was significantly worse in patients with visceral metastases (P=0.01). Results of Olink protein dynamic assay showed a significant downregulation of CEACAM5, TXLNA, PVRL4and ERBB2. Differential proteins between groups showed that there were no significant differential proteins between the hormone receptor-positive and negative groups at the baseline node, but 7 proteins were upregulated in the hormone receptor-positive group compared with the negative group at the progression node, with EMS-1, WIF-1, and hK14 being the most significant. Compared to primary resistance, trastuzumab secondary resistance appeared 4 proteins upregulated at the baseline node, with hK14 and CYR61 being the most significantly; and 33 proteins were upregulated at the progression node, with CYR61, CXL17, FURIN, and ABL1 being the most significantly. Patients with high expression of TLR3 and low expression of RET at the baseline node had longer PFS. Conclusions: This study demonstrates that pyrotinib in combination with albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and a manageable safety for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. PFS was shorter in patients with visceral metastases. TLR3 and RET were the proteins that significantly associated with PFS in patients. Citation Format: Huihui Li, Xiaochu Man, Sha Yin, Dongdong Zhou, Baoxuan Zhang, Shu Fang, Fangchao Zheng, Chao Li, Xinzhao Wang, Wei Huang, Linlin Wang, Qingqing He, Hui Fu, Yan Zhang, Changrui Liu, Lin Dong, Xianguang Zhao, Liang Xu, Xiao Sun, Bingjie Fan, Lihua Song, Zhengbo Zhou, Qiaorui Tan, Jinming Yu. Efficacy, safety and translational study of pyrotinib combined with albumin-bound paclitaxel as firstline treatment of HER-2 positive metastatic breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-07.
Li et al. (Thu,) studied this question.