Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in the second-line treatment for HER2-positive metastatic breast cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan（T-DXd） versus trastuzumab emtansine （T-DM1） in the second-line treatment of HER2-positive metastatic breast cancer， and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast03， a partitioned survival model was constructed， with a cycle of 3 weeks as the simulation of patients’ lifetime. The incremental cost-effectiveness ratio （ICER） was calculated by using quality-adjusted life years （QALY） as output indicators， and sensitivity analysis was used to verify the robustness of the basic analysis results； the cost-effectiveness of the second-line treatment for HER2-positive metastatic breast cancer was compared between T-DXd and T-DM1. RESULTS Under the premise of taking 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay threshold （257 094 yuan/QALY）， the T-DXd group also needed to pay more cost compared with T-DM1 group while obtaining incremental utility （0.69 QALYs）， and the ICER value was 1 850 478.40 yuan/QALY. The results of univariate sensitivity analysis showed that progression-free survival state utility value， T-DXd price， cost discount rate were factors that had a great influence on ICER value， but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis， when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY， the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China’s per capita GDP as the WTP threshold， compared with T-DM1， T-DXd is not cost-effective in the second-line treatment of HER2-positive metastatic breast cancer.

Real-world Efficacy and Safety Comparison of Neoadjuvant Treatment of HER2-positive Breast Cancer with TCbHP Versus AC-THP / 肿瘤防治研究

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Reform and Prospect of Systemic Therapy on HER2-positive Early-stage Breast Cancer / 肿瘤防治研究

In the past two decades, the survival of HER2-positive early-stage breast cancer patients has significantly improved with the development of HER2-targeted therapies. The focus has been placed on maximizing the clinical benefit of HER2-positive early-stage breast cancer by optimizing the treatment frameworks and therapeutic strategies in this field. In this paper, several important clinical studies of HER2-positive early-stage breast cancer in the neoadjuvant or adjuvant settings will be summarized and analyzed to provide clues for the development of personalized treatment strategies in the future.

Characteristics and Research Progress of Traditional Chinese Medicine in Treatment of HER-2-Positive Breast Cancer： A Review / 中国实验方剂学杂志

Human epidermal growth factor receptor-2 （HER-2）-positive breast cancer has higher predilection to metastasize and invade other organs， leading to poor prognosis. The anti-HER-2 drugs， such as trastuzumab， pertuzumab， and trastuzumab emtansinehas， can remarkably prolong the disease free survival （DFS） of patients. However， frequent multidrug resistance， tumor recurrence and metastasis， and adverse reactions such as cardiotoxicity and gastrointestinal discomfort caused by adjuvant therapy are still challenges for the treatment of HER-2-positive breast cancer. The understanding of breast cancer in traditional Chinese medicine （TCM） has a long history. In thousands of years of inheritance and innovation， a standardized treatment system with TCM characteristics has been gradually formed， which shows unique advantages and significant curative effects in breast cancer treatment. The treatment principles of ''treatment based on syndrome differentiation''， ''treatment based on stages and types''， ''treatment according to individual conditions''， and ''treatment of different viscera and viscera based on the toxin and pathogen'' are closely related to the precise treatment concept. In view of the challenges in the treatment of HER-2-positive breast cancer， such as multidrug resistance， tumor recurrence and metastasis， cardiotoxicity， and gastrointestinal discomfort， this paper summarizes the characteristics of TCM in reversing the multidrug resistance， inhibiting tumor recurrence and metastasis， prolonging DFS， improving prognosis， reducing adverse reactions caused by adjuvant therapy， and improving the quality of life after breast cancer surgery according to the principles of reinforcing healthy Qi and eliminating pathogen， and treatment based on syndrome differentiation. This article is expected to serve as a reference for TCM treatment of HER-2 positive breast cancer.

Comparison of adverse effects of trastuzumab with other drug combinations for the treatment of breast cancer: A review

OBJECTIVES: This study compares the adverse effects (AEs) associated with trastuzumab in the treatment of human epidermal growth factor receptor 2-positive breast cancer (HER-2 + BC) when used alone or in combination with chemotherapy or with tyrosine kinase inhibitors, so as to aid in rational treatment choices. MATERIALS AND METHODS: An electronic search was conducted on PubMed using the Mesh terms ‘BC’, ‘HER-2 positive’, ‘metastasis BC, ‘trastuzumab’, and ‘safety’. Data from 32 studies regarding AEs were extracted and categorised as trastuzumab + chemotherapy (T+C), trastuzumab biosimilar (Tb), trastuzumab + tyrosine kinase inhibitors+ chemotherapy (T+TKi+C), and trastuzumab + tyrosine kinase inhibitors (T+TKi). The data are presented as the mean percentage of AEs. The statistical comparison was represented by a box and whisker plot of the interquartile range value of AEs. RESULTS: AEs related to the gastrointestinal tract, skin, nervous, blood, and lymph were reported to be the most common in T+C, T+TKi+C, and T+TKi. Nausea, vomiting, diarrhoea, constipation, neuropathy peripheral, alopecia, rash, anaemia, leucopenia, raised aspartate transaminase and alanine transaminase were the most common complaints. AEs such as myalgia, nasopharyngitis, hypertension, and ejection fraction decrease was reported to be the most common in Tb. CONCLUSION: This study concluded that biosimilar of trastuzumab is safest for the treatment of HER-2-positive BC. Cardiovascular disorder is often reported in the biosimilar group, but this group has fewer AEs reported as compared with chemotherapy, and tyrosine kinase inhibitors groups related to other systems such as digestive, nervous, and respiratory. The choice of combination is depending on the type of BC and the condition of the patients. The patients must monitor for cardiotoxicity when the biosimilar of trastuzumab is used.

Advances in immunotherapy for human epidermal growth factor receptor 2-positive breast cancer / 中华微生物学和免疫学杂志

Human epidermal growth factor receptor 2 (HER2)-targeted therapy has greatly improved the prognosis of HER2-positive breast cancer. HER2-targeted therapy combined with chemotherapy dominated by trastuzumab+ pertuzumab is important in the neoadjuvant therapy, postoperative adjuvant therapy and late-stage standard treatment for HER2-positive breast cancer. Antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) have further improved the efficacy of therapy. However, advanced breast cancer will eventually get a recurrence or drug resistance. HER2-positive breast cancer is characterized by moderate immunogenicity with the presence of large tumor-infiltrating lymphocytes (TILs), which provides a theoretical basis for immunotherapy. The application of HER2-targeted cancer vaccines and immune checkpoint inhibitors is promising and would offer more treatment options for the patients.

Metformin inhibits proliferation and promotes apoptosis of HER-2 positive breast cancer cells possibly through the Hippo-YAP pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of metformin on the proliferation and apoptosis of HER-2-positive breast cancer cell line SKBR3 and explore the possible mechanism of its action.@*METHODS@#SKBR3 cells were treated with different concentrations (20-120 μmol/L) of metformin, and the changes in cell proliferation and colony formation ability were assessed using CCK-8 assay and crystal violet staining, respectively. Flow cytometry was performed to analyze cell apoptosis and cell cycle changes. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect mRNA expressions of YAP, TAZ, EGFR, CTGF, CYR61, E-cadherin, N-cadherin, vimentin and fibronectin in the treated cells, and the protein expressions of YAP and TAZ were detected using Western blotting; immunofluorescence assay was used to observe YAP/TAZ nuclear translocation in the cells.@*RESULTS@#Metformin treatment significantly inhibited the proliferation of SKBR3 cells (P < 0.05) in a concentration- and time-dependent manner. The results of flow cytometry showed that metformin significantly promoted apoptosis and caused cell cycle arrest at G1 phase in SKBR3 cells. Metformin treatment significantly down-regulated the mRNA expressions of YAP, TAZ, EGFR, CTGF and CYR61, N-cadherin, vimentin and fibronectin (P < 0.05) and up-regulated the expression of E-cadherin (P < 0.05); Western blotting results showed that YAP and TAZ protein expressions were significantly down-regulated in the cells after metformin treatment (P < 0.05). Immunofluorescence assay revealed that metformin treatment caused the concentration of YAP and TAZ in the cytoplasm, and significantly reduced their amount in the cell nucleus.@*CONCLUSION@#Metformin can inhibit proliferation and promote apoptosis and epithelal-mesenchymal transition of HER-2 positive breast cancer cells possibly by that inhibing YAP and TAZ expression and their nuclear localization.

Cost-effectiveness analysis of Ado-trastuzumab emtansine for the treatment of residual invasive HER2-positive breast cancer

ABSTRACT Objective Human epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancer cases. Ado-trastuzumab emtansine (T-DM1) is approved to treat residual HER2-positive breast cancer after neoadjuvant therapy. The aim of this study was to determine the quality-adjusted time with symptoms or toxicity and without symptoms or toxicity (Q-TWiST) of T-DM1 compared to trastuzumab for residual invasive HER2-positive breast cancer. Methods The authors developed an analytical model extracting individual patient data and estimated invasive disease-free survival and overall survival over a 30-year time horizon. Only direct costs from adjuvant treatment were considered as well as relapse treatment from Brazilian and American payer perspectives. Heart events were considered for utility and cost analysis. Results The 30-year projection utilizing the Weibull method estimated a mean invasive disease-free survival of 16.4 years for T-DM1 and 10.4 for Trastuzumab, in addition to a mean overall survival of 18.1 and 15.4 years, respectively. We determined a Q-TWiST gain of 3,812 years for the T-DM1 arm when compared to trastuzumab and an Incremental cost-effectiveness ratio per Q-TWiST of US$ 11,467.65 in the United States and US$ 3,332.73 in Brazil. Conclusion Ado-trastuzumab emtansine is cost-effective from both Brazilian and American perspectives.

Expression and clinical significance of KIF20A in HER2-positive breast cancer / 国际生物医学工程杂志

Objective:To explore the expression and clinical significance of KIF20A in HER2-positive breast cancer.Methods:The clinicopathological characteristics of 82 cases of HER2-positive breast cancer were retrospectively analyzed. The expression of KIF20A in tissues was detected by immunohistochemical method, and the expression of KIF20A in HER2 overexpression breast cancer and its relationship with clinicopathological characteristics were analyzed. The mRNA level of KIF20A in HER2-positive breast cancer tissues and normal tissues adjacent to cancer were analyzed by bioinformatics methods.Results:The positive expression of KIF20A was in the nucleus, forming brown-yellow particles. In HER2-positive breast cancer tissues, the positive high expression rate of KIF20A is 57.3%, while it is mainly low or no expression in the adjacent tissues. The high expression of KIF20A is significantly correlated with tumor size and pTNM stage, while the correlation with age and tumor grade is not statistically significant. The results of bioinformatics analysis suggest that the high expression of KIF20A in invasive breast cancer is significantly related to poor disease-free survival.Conclusions:KIF20A is abnormally expressed in HER2-positive breast cancer, which is related to the tumor grade and pTNM stage of HER2 overexpression breast cancer, and the high expression of KIF20A indicates a poor prognosis.

Research progress of targeted therapy for HER2 positive breast cancer with brain metastases / 医学研究生学报

Breast Cancer, nowadays, is the malignant tumor with the highest incidencein females.HER2 Positive Breast Canceraccounts for 20%-25% of the total, among which about 34% of patients with this type will occur brain metastasis.HER2 Positive Breast Cancer patients with brain metastasis, which seriously affects the quality of life, has a poor prognosis. Currently, surgery or radiotherapy is still the main treatment for brain metastasis. However, surgery is only applicable in localized brain metastasis, and it is obviously that terminaladverse reaction such as cognitive impairment can be causedby radiotherapy. Therefore, it is particularly important to discovery effective targeted drugs or new drug delivery methods for brain metastasis.This articlewill review the research progress of targeted therapy for brain metastases in HER2positive breast cancer.

Anti-HER2 Antibodies In Combination With Chemotherapy Or Chemotherapy-Free Regimens Targeting Her2-Positive Breast Cancer: A Systematic Review

@#Breast cancer is the leading cause of cancer-related death in female worldwide. Human epidermal growth factor receptor 2 (HER2) amplification is observed in approximately 20% of breast cancer cases and is associated with poor clinical outcomes. Dual HER2 blockade without chemotherapy represents an attractive therapeutic approach, and it remains unresolved if anti-HER2 therapeutic antibodies are sufficient to replace chemotherapy regimens. In this review, we discuss the approved therapeutic monoclonal antibodies (pertuzumab and trastuzumab) and antibody-drug conjugate (trastuzumab emtansine or T-DM1) for the treatment of HER2-positive breast cancer patients. In summary, phase II and III clinical trials have demonstrated that dual HER2 blockade (pertuzumab and trastuzumab) plus chemotherapy regimens confer better efficacy compared with dual HER2 blockade alone, or anti-HER2 antibody monotherapy, in HER2-positive breast cancer patients. Dual HER2 blockade (pertuzumab and trastuzumab) combined with chemotherapies (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel) yield superior response. Moreover, dual HER2 blockade (T-DM1 and pertuzumab) in combination with docetaxel represents a promising treatment regimen containing T-DM1. Ongoing clinical trials are assessing the optimal chemotherapy of choice with anti-HER2 antibodies combinations. In conclusion, improved outcomes are attributable to selection for the optimal chemotherapy regimen in combination with anti-HER2 antibodies instead of replacing chemotherapy altogether with the current line of anti-HER2 therapeutic antibodies.

Evaluation value of the MRI parameter and immunohistochemistry in the neoadj uvant chemotherapy for HER-2 positive breast cancer / 实用放射学杂志

Objective To explore the evaluation value of MRI parameters and immunohistochemistry in the neoadjuvant chemotherapy (NAC)for the HER-2 positive breast cancer.Methods 7 6 patients with locally advanced HER-2 positive breast cancer were analyzed retrospectively.According to the postoperative pathology,patients were divided into pathological complete response (PCR)group and non-PCR (Non-PCR)group.First,univariate and multivariate Logistic regression analysis were used to analyze the predictors of PCR,and then we assessed the evaluation value of the assessment model which was built on multivariate logistic regression.Results Univariate regression analysis showed that menstrual status,ER expression,K-i 67 expression,ADC value,tumor diameter, ΔADC%(NAC2－NAC0),ΔD%(NAC0－NAC2) had predictive value for PCR;the parameters ΔADC% and ΔD%,the expression of ER and K-i 67 were independent predictors of PCR based on multivariate Logistic regression analysis.The AUC of the assessment model model was 0.873.Conclusion Based on the heterogeneity of breast cancer,combine MRI with immunohistochemistry parameters could improve the prediction in the middle of NAC,and provide imaging basis for the adj ustment of follow-up chemotherapy regimen.

Growth differentiation factor 15 plays a role in predicting and monitoring the cardiotoxicity of epirubicin/cyclophosphamide-docetaxel-trastuzumab in the treatment of patients with HER-2 positive breast cancer / 实用肿瘤学杂志

Objective The aim of current study was to evaluate the effect of growth differentiation factor 15( GDF-15) on predicting and monitoring the cardiotoxicity of epirubicin/cyclophosphamide-docetaxel-trastuzumab(EC-D-T)in the treatment of HER-2 positive breast cancer patients. Methods Seventy-three patients with HER-2 positive breast cancer who received EC-D-T adjuvant therapy were enrolled. Serum levels of GDF-15,cardiac troponin I(cTnl)and amino terminal brain natriuretic peptide precursor(NT-proBNP)were measured before adjuvant therapy(M0)and after adjuvant therapy at 3 months(M3 ),6 months(M6 ),9 months(M9 ),12 months(M12 )and 15 months(M15 ). At the same time,patients underwent echocardiography at various time points to assess the left ventricular ejection fraction(LVEF). The cardiotoxicity of this study was defined as:(1)LVEF level decreased by ≥10% after treatment and the absolute value of LVEF was below 53% (normal);(2) heart failure,acute coronary syndrome or severe life-threatening heart rate abnormal. Results After initiation of EC-D-T treatment,the level of LVEF gradually decreased. Dur-ing the whole study,a total of 21(28. 8% )patients developed cardiotoxicity. At the same time,patients with cardiotoxicity had signifi-cantly higher levels of GDF-15 at M0 and cTn1 at various time points than those without cardiotoxicity. The level of ProBNP was comparable to those without cardiotoxicity. In addition,Univariate logistic regression analysis showed that baseline GDF-15 might af-fect the risk of cardiotoxicity. Multivariate logistic regression analysis showed that only cTnl level was an independent predictor for the risk of cardiotoxicity, while NT-proBNP level did not predict the risk of cardiotoxicity. Conclusion The incidence of cardiotoxicity in patients with HER-2 positive breast cancer after receiving EC-D-T is high,and GDF-15 can predict and monitor the risk of cardiotoxicity.

Analysis and validation of PI3K/AKT signaling pathway associated with overall survival time of patients with HER2-positive breast cancer / 解放军医学杂志

Objective To analyze and validate the key molecular targets correlated with the overall survival of patients with HER2-positive breast cancer.Methods First,the survival time and transcriptome data of patients with HER2-positive breast cancer in stage Ⅰ / Ⅱ and Ⅲ/Ⅳ were downloaded from the TCGA database.The significantly differential genes between overall survival ＜2 years and ＞8.5 years in stage Ⅰ / Ⅱ were picked out by edgeR package,and the pathways were enriched by KEGG.Similarly,the differential genes between overall survival ＜2 years and ＞7 years in stage Ⅲ/Ⅳ were analyzed.Furthermore,KEGG pathway analysis was performed using the differential genes overlapped by stage Ⅰ /Ⅱ and Ⅲ/Ⅳ.Second,the relationships between the expression levels of key node genes and other genes in enriched pathway and the overall survival of patients with HER2-positive breast cancer were validated by KMplot database.Last,the correlation between the activity of pathway enriched in KEGG and the resistance to anti-HER2 treatment was validated in HER2-positive breast cancer cell line BT474.Results In patients with stage Ⅰ / Ⅱ HER2-positive breast cancer whose overall survival was ＜2 years,PI3K/AKT was the 9th signaling pathway enriched by up-regulated differential genes.In patients with stage Ⅲ/Ⅳ whose overall survival was ＜2 years,PI3K/AKT was the 2nd signaling pathway enriched by up-regulated differential genes.Furthermore,PI3K/AKT was the first signal pathway enriched by the overlapping upregulated genes of patients in stage Ⅰ / Ⅱ and Ⅲ / Ⅳ whose overall survival was ＜2 years.Patients with high expression of PI3K and AKT (key node genes) or CFAP221 and COL4A6 (other genes) of PI3K/AKT pathway had shorter overall survival than those with low expression.PI3K inhibitors could enhance the growth inhibitory effect of HER2 small molecule inhibitor on HER2-positive breast cancer cell line BT474.Conclusions The overexpression of PI3K/AKT pathway is associated with the shorter overall survival in HER2-positive breast cancer patients,and associated with anti-HER2 resistance in HER2-positive breast cancer cell line.

The inhibitory effect and molecular mechanism of delphindin on HER-2 positive breast cancer / 天津医药

@#Objective To investigate the inhibitory effect and molecular mechanism of delphinidin (Dp) on HER-2 positive breast cancer. Methods The HER-2 positive breast cancer cells (MDA-MB-453 and BT-474) were treated with different concentrations of delphinidin (10，20，40，80 and 160 μmol/L) for 48 hours. The same concentration of DMSO was used as the solvent control. CCK-8 method was used to measure the effect of Dp on cell activity, and half maximal inhibitory concentration (IC50) was calculated to determine the concentration of subsequent experiments. The cells were treated with different concentrations of Dp (20, 40 and 80 μmol/L) for 48 hours. HE staining was used to observe the cell morphological changes. Flow cytometry was used to analyze the cell cycle. Cell apoptosis rate was detected by TUNEL assay. The phosphorylation levels of NF - κB signaling pathway related proteins were determined by Western blot assay. Results Delphinidin inhibited the proliferation of MDA-MB-453 and BT-474 in the concentration ranges of 10，20，40，80 and 160 μmol/L (IC50: 41.02 and 60.97 μmol/L). In the concentrations of 20，40 and 80 μmol/L, compared with the control group, it was found that some cells were detached, floated and lysed, and the cell volume was decreased, the proportion of cells in G2/ M phase and the apoptosis rate were increased in DP treatment groups. Compared with the control group, the expression levels of p-NF-κB/p65, p-IκBα, p-IKKα/β and p-PKCα were significantly decreased in the 40 and 80 μmol/L Dp treatment groups, while the expression levels of IκBα, IKKα, IKKβ and PKCα were increased in the Dp treatment groups (P＜0.05). Conclusion Delphinine can inhibit the proliferation of breast cancer cells by blocking the NF-κB signaling pathway and inducing the G2/M cycle arrest and apoptosis of MDA-MB-453 and BT-474 cells. Key words：receptor, epidermal growth factor; antineoplastic agents, phytogenic; breast neoplasms; cell cycle; delphinidin;HER-2 positive breast cancer; NF-κB signaling pathway

A Cost-Effectiveness Analysis of Adjuvant Trastuzumab Regimens in HER2-Positive Early Breast Cancer / 中国药学杂志

OBJECTIVE: To advocate Patient Assistant Program Projects (PAP Projects) decision-making, this study assesses the long-term cost-effectiveness of 1-year adjuvant trastuzumab therapy for women with human epidermal growth factor receptor 2 (HER2) positive early breast cancer. METHODS: A Markov model tracked yearly patients' transitions between five health states. The cycle length was 1 year and the sum was 45. From the perspective of the China health insurance system, the direct medical cost was estimated based on a survey of clinical expert panels. A discounting rate of 3% was used to discount direct medical cost and health outcomes. Utility and transition probabilities were retrieved from the HERA trial and literature. To estimate the direct medical cost, a survey of clinical expert panels was conducted. The cost of trastuzumab and HER2 test based on Roche. The key factor of the model was realized by one-way sensitivity analysis. The result of a probability sensitivity analysis conducted by Monte Carlo simulation was expressed as an incremental cost-effectiveness scatter plot. RESULTS: Without PAP Projects in Guangzhou, the adjuvant trastuzumab treatment prolonged 1.79 QALYs when the cost increased ¥53 301 and the Incremental cost-effectiveness ratio (CER) was ¥29 731/QALY, which is cost-effective based on Guangzhou's per capita GDP in 2015. With PAP Projects, the adjuvant trastuzumab treatment was totally cost-effectiveness. The sensitivity analysis demonstrated that the model was moderate. CONCLUSION: One year adjuvant trastuzumab treatment is a cost-effective therapy for patients with HER-2 positive breast cancer. With PAP Projects in Guangzhou, the adjuvant trastuzumab treatment is projected to be associated with improved QALYs and reduces direct medical costs, compared with the standard chemotherapy, represents a dominant treatment option among patients with HER2-Positive Early Breast Cancer. PAP Projects in Guangzhou should be persisted and spread in China.

Therapeutic strategy for HER-2-positive advanced breast cancer / 中国肿瘤临床

Patients with HER-2-positive advanced breast cancer were associated with poor prognosis. Meanwhile, HER-2-targeted ther-apy has dramatically improved survival and prognosis among breast cancer patients. Over the years, multiple HER-2-targeting drugs stepped into clinical practice, and the targeted agents are now considered as the standard of care in the first-line setting and beyond. This review basically summarizes the importance of HER-2-targeted therapy, the significance of the clinical trial results, and the clinical practice guidelines for the management of patients with HER-2-positive advanced breast cancer.

Clinical Observation of Trantuzumab Combined with Preoperative Adjuvant Chemotherapy in the Treatment of Her-2 Positive Breast Cancer / 中国药房

OBJECTIVE:To observe the effect of trantuzumab combined with preoperative adjuvant chemotherapy in the treat-ment of human epidermal growth factor receptors 2 (Her-2) positive breast cancer,and to investigate its clinical value. METH-ODS:80 patients with Her-2 positive breast cancer were selected and randomly divided into observation group and control group, with 40 cases in each group. The control group received routine preoperative adjuvant chemotherapy+modified radical mastectomy for Her-2 positive breast cancer;observation group was additionally treated with trastuzumab intravenously before operation,initial dose of 4 mg/kg,followed by 2 mg/kg,once a week,for consecutive 3 weeks,on the basis of control group. The effects of two regimen on the expression of HER-2,CD-34,MGA,E-cadherin and GCDFE-15 in Her 2 positive breast cancer focus were com-pared between 2 groups. ADR and follow-up survey were recorded. RESULTS:Compared with before chemotherapy,the expres-sion of HER-2(+)in observation group increased significantly,while that of HER-2(+ + +)decreased significantly;MGA posi-tive rate and GCDFP-15 positive rate decreased significantly while E-cadherin positive rate increased significantly;MDV of CD34 expression decreased significantly,with statistical significance(P0.05). CONCLUSIONS:Trastuzumab combined with preoperative adjuvant chemotherapy have good clinical efficacy and safety,and it can effectively reduce related indicator of Her-2 positive breast cancer focus. So it has positive significance in reducing recurrence and metastasis of breast cancer.

Efficacy and mechanism of FW-04-806 against HER2-positive gastric cancer cell lines / 中国药理学通报

Aim To investigate the efficacy and mech-anism of FW-04-806 against HER2-positive gastric cancer cell lines,and the combination effect of FW-04-806 with lapatinib. Methods MTT assay was used to assess cell proliferous inhibition of FW-04-806 . The in-hibitory effect of colony formation was tested by colony formation. The protein expression, apoptotic induction and cell cycle arrest were detected by flow cytometry. Co-immunoprecipitation was used to investigate protein-protein interactions. The expression change of proteins was showed by immunohistochemistry. Western blot was applied to reveal the protein expression of related pro-liferous and apoptotic signaling pathway. The tumor growth inhibition was evaluated in tumor xenograft model. Results FW-04-806 obviously inhibited cell proliferation and colony formation in HER2 positive gastric cancer cell lines NCI-N87, OE19, with IC50 of (24. 17 ± 0. 02 ) , ( 29. 61 ± 0. 03 ) μmol · L-1 , re-spectively;FW-04-806 induced G2-M arrest and apop-tosis in a dose-dependent manner;200 mg · kg-1 of FW-04-806 showed tumor growth inhibition of 48. 0%( P < 0. 01 ) . In addition, FW-04-806 dissociated Hsp90/CDC37 complex, followed by degradation of HER2 and Akt,inhibiting the phosporylation of HER2, Akt and ERK, and increasing expression of apoptotic proteins,such as cleaved caspase-3 and cleaved parp. Furthermore,the combination of FW-04-806 with lapa-tinib in vitro was synergistic in NCI-N87 , which en-hanced the inhibition of cell proliferation and increased apoptotic rates. Conclusions FW-04-806 shows po-tent efficacy against HER2-positive gastric cancer cell lines in vitro and in vivo;FW-04-806 is synergistic with lapatinib.

A novel HER2-targeted drug:T-DM1 antibody-drug conjugate / 中国肿瘤临床

T-DM1 is a novel antibody-drug conjugate that has similar biological activity with that of trastuzumab. T-DM1 specifically delivers DM1, the effective anti-microtubule drug, into the cytoplasm of tumor cells with HER2 overexpression. The efficacy of T-DM1 monotherapy is better than lapatinib in combination with capecitabine and T-DM and is expected to become the standard second-line treatment for HER2-positive advanced breast cancer drugs. Clinical trials that compare T-DM1 with trastuzumab joint taxane as the first-line of treatment for advanced breast cancer trials are currently being performed. T-DM1 is a brand new anti-HER2 drug after trastuzumab. U.S. FDA already approved T-DM1 as a drug for the treatment of HER2-positive advanced breast cancer patients.