HER2阳性乳腺癌患者预后较差，曲妥珠单抗靶向治疗虽有一定疗效，但存在原发或继发耐药。乳腺癌微环境中CAF与曲妥珠单抗治疗耐药有关，但其具体机制尚不明确。我们前期研究发现CAF及其分泌的外泌体可降低曲妥珠单抗治疗的敏感性；同时，CAF外泌体可高表达UCA1等LncRNA，并在曲妥珠单抗治疗后表达增加；CAF外泌体与乳腺癌细胞共培养后，可上调其LncRNA UCA1的表达，并激活PI3K信号通路及促使细胞发生EMT。故我们推测CAF外泌体递送相关LncRNA供乳腺癌细胞摄取后，激活其PI3K信号通路并诱导细胞发生EMT，从而降低曲妥珠单抗治疗的敏感性。在本研究中，我们拟明确CAF及其外泌体递送相关LncNRA介导曲妥珠单抗治疗耐药的机制，并在此基础上探讨抑制CAF外泌体的分泌及其LncRNA的表达是否可逆转曲妥珠单抗治疗的耐药，从而为提高HER2阳性乳腺癌患者疗效提供依据。

HER2 positive breast cancer has poor prognosis, which can be partly improved by trasutuzumab treatement, but primary or secondary trastuzumab resistance still remains. Recent studies demonstrated that CAF in breast cancer microenvironment was associated with trastuzumab resistance. However, the detail mechanisms remain unelusive. Our previous study found that CAF and its secreted exosomes would decrease trastuzumab treatment sensitivity. In addition, CAF exosomes could overexpress several LncRNA, such as UCA1, which expression will be enhanced by trastuzumab treatment. Co-culture of CAF exosomes and breast cancer can upregulate LncRNA UCA1 expression level in cancer cells, which would lead to PI3K signaling pathway activation and induce EMT in tumor cells. Therefore, we hypothesize that CAF exosome-mediated delivery of LncRNA, which can be uploaded by breast cancer cells, can activate PI3K signaling pathway and induce EMT in tumor cells, thus to decrease trastuzumab treatment sensitivity. In this current study, we plan to find out the clear relationship between exosomal transfer of CAF-derived LncRNA and trastuzumab treatment resistance, and to investigate whether targeting CAF exosomes secretion and its LncRNA expression would reverse trastuzumab treatment resistance, which would provide supports to improve the treatment efficacy in HER2 positive breast cancer.