For HER-2 positive breast cancer, HER-2-targeted agents combined with agents that target downstream signaling or alternative pathways, and endocrine therapy has been investigated in clinical settings. This paper focuses on studies involving phaseⅡand phaseⅢclinical trials for new targets with enhanced clinical applications, including novel small molecular targeting agents, monoclonal antibody-targeted drugs, monoclonal antibody conjugates, dual target drug combination therapy, drug targeting combined with endocrine and targeted chemotherapies, trastuzumab subcutaneous injection, and HER-2 tumor vaccine.

Approximately 70％ advanced breast cancer will develop bone metastases.Bone metastases can cause a series of complications such as skeletal-related events,seriously affecting the quality of life of the patients.Therefore,it is very important to choose the reasonable and effective treatments.Bisphosphonates are the standard treatments of bone metastatic breast cancer,denosumab may also be a reasonable alternative to bisphosphonates in the near future,while chemotherapy,endocrinotherapy and targeted therapy are the basic treatments of advanced breast cancer,combined use of various treatments will get the best efficacy.

BRCA1 is a breast cancer susceptibility gene,which related to breast cancer,ovarian cancer and other cancers.The occurrence of breast cancer is related to gene mutation.In recent years,more and more researches indicated some clinical characteristics of breast cancer relevant to BBCA1,such as the reaction to chemotherapy,radiotherapy and operation. This review will provide guidance for future application of BRCA1 in clinic by introducing the clinical progression of it.

Objective: To study the effect of new photosensitizer Chlorophyl-derivative (CPD4) combined with Adriamycin on cell cycle and cell proliferation of MCF-7 breast cancer cell line and to investigate the mechanism of combination therapy. Methods: A new type of photosensitizer and traditional chemotherapy drug Adriamycin (ADM) were used to treat breast cancer cell line MCF-7. Flow cytometry was employed to detect apoptosis rate and cell cycle distribution in ADM group, group with photodynamic effect and the combined group. The influence of ADM on the mean fluorescence intensity and the changes in the mean fluorescence intensity after CPO4 (1.5μg/mL) treatment were analyzed. Results: The apoptosis rate of the combination group was higher than that in the other two groups, with statistical significance (P＜0.01). Photodynamic effect caused G_0/G_1 phase arrest in MCF-7 cells. Low concentration of ADM increased the number of G_2/M phase cells. The percentage of G_2/M phase cells was increased in the combination group. No significant difference was found in the mean fluorescence intensity between ADM pretreated MCF-7 cells for 24 hours and 48 hours and the control group (P＞0.05). Pretreatment of MCF-7 cells with ADM increased the volume of photosensitizer CPD4 into the cells. The mean fluorescence intensity at 2 hours after CPD4 incubation was the highest. Conclusion: ADM can increase the amount of CPD4 into the MCF-7 cells. Photodynamic therapy com-bined with Adriamycin has a synergistic effect on MCF-7 cells.

Objective:To analyze the prognostic factors in patients with metastatic breast cancer (MBC). Methods:A total of 205 patients with pretreated MBC were included in this study. These patients were admitted to the Tianjin Medical University Cancer Insti-tute&Hospital and had undergone radical surgery of breast cancer between January 2008 and December 2010. The clinicopathologic information of the patients was collected in this retrospective analysis. Results: The median overall survival of the patients was 32 months (1 month to 132 months). Luminal A, Luminal B, HER-2 overexpression, and triple-negative patients had a median overall sur-vival of 36 months (4 months to 132 months), 32 months (7 months to 122 months), 29 months (1 month to 85 months), and 24 months (1 month to 98 months), respectively. Univariate analysis showed that lymph node metastases, clinical stage, molecular type, visceral disease, first multiple metastatic sites, and shorter metastasis-free interval were significantly associated with poor outcomes. In multivar-iate analysis, lymph node metastases, clinical stage, molecular type, visceral metastasis, and the number of first metastatic sites were significant predictors of patient survival. Conclusion:Lymph node metastasis, clinical stage, triple-negative breast cancer, and visceral metastasis were used as independent poor prognostic indicators for survival in patients. Results of this study may assist physicians in evaluating the survival potential and determining the appropriate therapeutic strategy for MBC patients.

Objective: To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers. Methods: Thir-ty-one healthy volunteers were grouped into three palonosetron hydrochloride dosage regimens of 0.125, 0.25, and 0.5 mg. The plasma concentrations of palonosetron were determined by ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). DAS 2.1 software was applied to assess the plasma concentration-time data. Results:After intravenous injection of 0.125, 0.25, and 0.5 mg palonosetron to the subjects, the AUC0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t1/2 values were (27.2±9.5), ( 27.2±6.5), and (31.4±5.6) h. Palonosetron exposure increased proportionally with the dose range of 0.125 mg to 0.5 mg. The correlation coefficient was 0.998. No grade 3 or grade 4 toxicity was observed during the study. Con-clusion:A rapid, sensitive, and selective UPLC-MS/MS method for palonosetron quantification in human plasma was developed and validated. All the participants indicated high tolerance throughout the study. Our data showed that palonosetron exhibits linear pharma-cokinetics over the the dose range of 0.125 mg to 0.5 mg.

Objective: Angiosarcoma of the breast is a rare and heterogeneous entity and its overall incidence is reported as 0.04% of primary breast cancer and as 8% of breast sarcoma approximately. To retrospectively analyze the clinical features and prognosis of breast angiosarcoma, 13 patients were identified by mammary pathologists in Tianjin Medical University Cancer Institute and Hospital from October 1975 to June 2009. Methods:Kaplan-Meier method was carried out to analyze different tumor size, tumor margins and histological grade. Prognosis was tested with univariate analysis by Log-rank test. Results: Median and mean age at diagnosis were 48 years and 44 years, respectively. The duration of follow-up ranged from 7 to 98 months (median, 50 months). All patients underwent surgical excision. Two patients received chemotherapy. Eight patients succumbed to recurrence and distant metastasis. Conclusion:Angiosarcoma of the breast has an exceedingly poor prognosis. The median disease-free survival (DFS) and overall survival (OS) were 28 months and 45 months, respectively. Both tumor size and surgical margins were associated with prognosis (P<0.05). Patients with high histological grade had a tendency of short OS (P>0.05) and a high risk of recurrence and metastasis (P<0.05).

Objective To construct the recombinant RIP3 over-expressed plasmids and transfect them in breast cancer MCF7 cells, and identify the expression and localization of fusion protein, as well as its effect on the death way of MCF7 cells. Methods The expression levels of RIP3 mRNA in four breast cancer cell lines and normal mammary epithelial cells were detected by reverse transcription polymerase chain reaction (RT-PCR). The RIP 3 coding sequence was amplified by polymerase chain reaction and subcloned into mCherry vector to construct recombinant plasmids. The plasmids were transfected into MCF7 cells by lentivirus after DNA sequencing, then screened by basticidin (4 mg/L) for 1 week. The efficiencies of RIP3 expression were validated by Western blotting assay. The death way of mCherry-RIP3-MCF7 cells was observed under the treatment of TNF-αand Z-VAD-FMK. Results The lowest expression of RIP3 mRNA was found in MCF7 cells. The sequencing results validated the well recombinant plasmids. The expression of mCherry-RIP3 fusion pro-tein with a molecular weight of 85 ku was detected by Western blot assay. The mCherry-RIP3 expression enhanced the sensi-tivity of MCF7 cells to TNF-αand Z-VAD-FMK induced cell death. Conclusion The recombinant RIP3 over-expressed plasmids were successfully constructed, and the stable MCF7 cells with ectopic RIP3 transfection were obtained. The mCher-ry-RIP3 fusion protein was expressed in the cytoplasm and was conformed to mediate TNF-αinduced necroptosis.

Objective:To evaluate the effectiveness and safety of using apatinib in the treatment of refractory triple-negative advanced breast cancer. Methods:Eight cases of advanced triple-negative breast cancer patients confirmed via histopathology, who were previously treated with anthracycline, taxane, gemcitabine, capecitabine, and 500 mg/d apatinib in our hospital from July 2015 to November 2016, were retrospectively analyzed. The time of disease progress, effective rate, clinical benefits, and side effects were observed. Results:Eight patients were administrated with an average of 4 treatment cycles, and the effects were evaluated after 2 weeks. Four patients exhibited partial remission, 3 had a stable disease, and 1 had a progressive disease. The disease control rate was 87.5%, and the median progression free survival was 4.2 months. The main side effects were hand-foot syndrome (3/8), bone marrow arrest (4/8), hypertension (2/8), proteinuria (3/8), hemoptysis (1/8), nausea (2/8), and fatigue (2/8). Most of these side effects were tolerable. Conclusion:Apatinib can effectively and tolerably prolong survival time and improve the quality of life of patients with advanced triple-negative breast cancer.

Objective To profile the intraspecific type of Trichophyton mentagrophytes clinically isolated from different anatomical sites of patients, and to compare the performance of different target sites for the identification of Trichophyton mentagrophytes complex strains. Methods A total of 48 Trichophyton mentagrophytes strains, which were clinically isolated from Department of Dermatology, Wuhan No. 1 Hospital in the latest 3 years, were included in this study. The phenotypes of these Trichophyton mentagrophytes isolates were primarily determined by morphological observation and the urease test. PCR was performed to amplify the nuclear ribosomal internal transcribed spacer(ITS) region and the D1?D2 domains of the large?subunit ribosomal DNA(28S rDNA)followed by DNA sequencing. Then, Clustal X2 software and MEGA 6.0 software were used to analyze the ITS and D1?D2 sequences and to build phylogenetic trees by the maximum?likelihood method (bootstrap = 2000). Results As the ITS sequence?based phylogenetic tree showed, the probability that the 48 isolates were grouped into the Trichophyton interdigitale clade reached 92%. However, Trichophyton interdigitale could not be effectively differentiated from Trichophyton quinckeanum by the D1?D2 sequence?based phylogenetic tree. In addition, Trichophyton interdigitale showed various appearances, including woolen type, downy type, cream type, powdery type and granular type. Conclusions Trichophyton mentagrophytes can be identified to the species level based on the sequence of ITS region, which shows higher efficiency in identifying Trichophyton mentagrophytes complex than the D1?D2 domains. Morphological characteristics can not serve as the basis for intraspecific typing of Trichophyton mentagrophytes.