Activation of the mammalian target of rapamycin (mTOR) signaling pathway is an important mechanism of resistance to endocrine therapy in breast cancer. Everolimus, an mTOR inhibitor, has been shown to increase the efficacy of endocrine therapy and overcome resistance to endocrine therapies. Clinical studies have suggested that everolimus combined with endocrine therapy prolongs progression-free survival in hormone receptor-positive breast cancer patients. However, because breast cancer includes a group of highly heterogeneous tumors, patients may have different responses to everolimus. Therefore, finding biomarkers that can predict a patient's positive response or resistance to everolimus is critical. Numerous preclinical studies have shown that PIK3CA/PTEN mutations are predictive of sensitivity to everolimus; however, clinical trials have not confirmed the correlation between mutation status and clinical response. KRAS or BRAF mutations can bypass the phosphatidylinositol 3-kinase pathway; therefore, mutations in KRAS or BRAF may lead to resistance to mTOR inhibitors, and preclinical studies have shown that PIK3CA mutant cells which also contain KRAS mutations are resistant to everolimus. However, there are no clinical data in breast cancer patients to support this conclusion. Therefore, large-scale clinical studies are needed to identify biomarkers of efficacy and resistance to everolimus.
Biomarkers* ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Everolimus* ; Humans ; Phosphatidylinositol 3-Kinase ; Sirolimus

As a breakthrough of precision medicine,intra-tumor heterogeneity is a research hotspot and is correlated to tumorigenesis,metastasis and resistance to therapies.In breast cancer,evidence of intra-tumor heterogeneity has been documented by numerous studies and it is the main obstacle to find ideal tumor markers and personalized medicine.Further analysis including the feature and generation mechanism of intra-tumor heterogeneity and the methods to assessment intra-tumor heterogeneity in the clinic are the key to cancer precision medicine.

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/drug therapy* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Receptor, ErbB-2

Brain metastasis (BM) is considered one of the major causes of mortality in breast cancer patients.BM develops more frequently in triple-negative breast cancer and human epidermal growth factor receptor 2 (HER2)-positive breast cancers,while the incidence of BM in hormone receptor positive is much lower.Mutations and expression of BM of breast cancer are differ from their primay tumors.Importantly,some therapeutic actionable mutations can be present in the BM while not in the primary tumors.Current targeted therapeutics in BM of breast cancers are limited,and drugs used have proven effects on the primary tumors but lack specificity for the BM.The identification of genomic and expressional alterations specific to BM are crucial to the development of BM specific targeted therapies.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Humans ; Female ; Breast Neoplasms/pathology* ; Multiomics ; Trastuzumab ; Receptor, ErbB-2/genetics* ; Machine Learning