基于激素受体和HER2受体表达情况对乳腺癌进行分子分型以实现个性化药物治疗是精准医学在临床应用的典范，但目前同型患者的治疗效果仍存在差异，临床上需要更精准的分型和标志物的发现。多项研究表明糖链肿瘤标志物是诊断并刻画人类肿瘤细胞特征的重要标志物。因此，本项目以精准医学理念为指导，采用药物分析新技术与方法，建立快速、灵敏的糖蛋白N-糖链酶解和定量分析新方法，开展不同分子分型乳腺癌患者与健康人体液样品、乳腺癌与正常细胞中糖基动态差异化研究，结合多维度药学统计学方法，筛选乳腺癌糖基化标志物；根据临床上针对不同分子分型乳腺癌采用的精准药物治疗方案，以内分泌治疗药他莫昔芬、化疗药多西他赛和分子靶向治疗药曲妥珠单抗等为研究对象，对不同分型乳腺癌患者和细胞系给药后糖基化水平的动态变化进行对比研究，建立细胞和整体水平之间糖基化的联系及其动态变化规律，为乳腺癌的临床诊断、分型和个性化药物治疗方案评价提供依据。

Individualized drug treatment on breast cancer based on molecular subtyping by hormone receptors and HER2 receptor, is a classic application of precision medicine on clinical cancer treatment. However, the diversity of drug therapeutic effect on the same molecular subtyping breast cancer still exist. Therefore, it is necessary to discover more precise biomarkers and more accurate subtypes of breast cancer. Previous studies well documented that malignant transformation and cancer progression result in fundamental changes in the glycosylation patterns of human carcinoma. Accordingly, based on the core concept of precision medicine and the application of new techniques and strategies of pharmaceutical analysis along with multi-dimensional statistical methods, the project is designed to discover potential glycan disease markers of breast cancer by investigating the dynamic differentiation of protein glycosylation between different molecular subtyping breast cancer patients and healthy people; breast cancer cell lines and control cells. Develop a high-throughput glycomics platform by establishing a rapid and sensitive qualification and quantification strategy for protein N-glycosylation and an advanced pre-treatment method for enzyme release of N-glycans. Based on the precision individualized drug therapies on different molecular subtyping breast cancer in clinical application, tamoxifen of endocrine therapy, docetaxel of chemotherapy and trastuzumab of molecular targeted therapy are selected, to comparatively study the dynamic response of protein glycosylation in different molecular subtyping breast cancer patients and breast cancer cell lines after individualized drug therapies, and to build connections and alteration patterns between cellular and individual level. The study would provide new basis in the clinical diagnosis, precision subtyping and individualized drug therapy in breast carcinoma.