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Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.
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s Triple-negative breast cancer (TNBC), a heterogeneous tumor that lacks the expression of estrogen receptor (ER), proges-terone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is more aggressive and tends to recur or metastasize. In contrast to other breast cancer subtypes, no approved endocrine or targeted treatments exist for TNBC. Therefore, identification of the prognosis characteristisics and potential therapeutic targets of TNBC could facilitate early personalized treatment. Owing to the rapid development of various technologies, researchers are increasingly focusing on the integration of "big data" and biological sys-tems, which is referred to "omics," as means of resolving it . Here, we review the recent progress in transcriptomics and proteomics re-search on TNBC.
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Objective To investigate whether MT1-MMP is involved in the inhibition effect of curcumin on the proliferation and invasion of breast cancer cell and the mechanism . Methods Firstly, MCF-7 cell lines transfected by MT1-MMP eukaryotic expression vector was established. We divided all cells into 3 groups,including null vector transfection group, non-transfected and transfected group with different concentrations of curcumin. The expression of MT1-MMP protein, the proliferation and invasion ability were respectively analyzed by western blot, transwell method, and cell counting kit-8 (CCK-8). Results The expression of MT1-MMP was inhibited by curcumin. Transwell and CCK-8 experiment indicated the proliferation and invasion abilities of MT1-MMP transfected MCF-7 cells were inhibited by curcumin in a concentration dependent manner. Conclusion The inhibition value of curcumin on proliferation and invasion is probably due to its ability to inhibit the expression of MT1-MMP.
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Objective To evaluate the clinical value of early intervention of second-line treatment for advanced breast cancer patients who experienced elevated tumor marker without any evidence for progress on imaging after effective first-line treatment. Methods We recruited 42 metastatic breast cancer patients experiencing elevated tumor marker (CEA or CA-153) meanwhile, who had merely increased tumor markers again in regular review after effective first-line treatment. Patients were divided into two groups: 20 patients in treatment group were given second-line treatment (palliative chemotherapy); 22 patients in observation group insisted on regular follow-up without any changing of treatment strategy. We mainly evaluated PFSmarker , which was defined as the time between tumor markers increase and disease progression. Results CEA and CA-153 in patients with advanced breast cancer showed a tendency to decrease after first-line chemotherapy , which can be reduced again by second-line treatment while increased in regular review , and the observation group continued to rise until disease progressed. The PFSmarker in treatment group was 13.65 (6 ~ 24) months while that of the observation group was 8.18 (3 ~ 15) months. The difference of PFS between these two groups was statistically significant (P < 0.05) and the median time to disease progression in treatment group was significantly longer than that in observation group. Conclusions Early intervention of second-line treatment for advanced breast cancer patients who only experienced elevated tumor marker after effective first-line treatment could slow down disease progression and improve the quality of life.
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<p><b>OBJECTIVE</b>To examine the expression pattern of membrane type-1 matrix metalloproteinase (MT1-MMP) in breast carcinomas.</p><p><b>METHODS</b>Forty-three breast cancer tissues were collected and examined for MT1-MMP protein and mRNA expressions using immunohistochemistry, semi-quantitative RT-PCR and in situ hybridization.</p><p><b>RESULTS</b>Immunohistochemistry of the breast cancer specimens showed MT1-MMP immunoreactivity on the cancer cell membrane. MT1-MMP mRNA was located in the stromal cells surrounding the breast cancer nest as shown by in situ hybridization. MT1-MMP mRNA expression was detected in all of the carcinomas, but its level was significantly lower in immunohistochemically negative specimens than in positive ones (0.547=0.0886 vs 0.759=0.0802, Plt;0.01).</p><p><b>CONCLUSION</b>MT1-MMP is very likely produced by stromal cells surrounding the breast cancer nest and anchored on the cell membrane after activation.</p>
Subject(s)
Female , Humans , Breast Neoplasms , Genetics , Metabolism , Immunohistochemistry , In Situ Hybridization , Matrix Metalloproteinase 14 , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Tumor Cells, CulturedABSTRACT
Breast cancer is one of the most common malignancies in women. Over these years, the morbidity of metabolic syndrome (MS) has also been increasing in China, probably due to changes in economies and lifestyles. As a result, the association to between these two diseases has at tracted much attention. Results demonstrated the presence of MS was associated with breast cancer risk, and the risk became higher when more MS components were present compared to no components. Moreover, a specific association was indicated between MS and breast cancer recurrence and metastasis to some extent as well. Further, for breast cancer patients, being diagnosed with MS can increase the mortality and lead to poor prognosis. The mechanisms underlying the association is not clear yet, but several factors are speculated to be the possible causes, including the elevated level of insulin, insulin like growth factor-1, leptin and pro-inflammatory cytokines, the decreased level of adiponectin as well as the interaction between DBC1 and SIRT1. The prognosis of patients with breast cancer combined MS can be improved by means of changing diet habits, increasing physical activities and drug-intervention. Although the specific mechanisms underlying the association are still need to be elucidated, better understanding of the association must help us with new strategies for the prevention and treatment of breast cancer.
Subject(s)
Humans , Adiponectin , Breast Neoplasms , Insulin , Metabolic Syndrome , PrognosisABSTRACT
As a tubulin stabilizer, taxanes are widely used in the treatment of breast cancer, ovarian cancer, non-small-cell lung cancer (NSCLC),and part of head and neck malignant tumors, and were confirmed to be significantly effective.However, taxanes-induced peripheral neuropathy(TIPN) still affects the quality of life and psychological status of patients to varying degrees, severe cases can lead to dose reduction, and even chemotherapy interruption.In this paper, we summarize the pathogenesis, risk factors, clinical assessment, the progress of prevention and treatment of TIPN, to provide the basis for the prediction and early prevention of TIPN in the clinical administration, thus we can improve patients’ quality of life while extending their survival.
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Objective To explore the incidence and predictive factors of anemia induced by chemothera-py in early breast cancer patients. Methods 400 early breast cancer patients treated by taxane-based regimens from 2009 to 2011 in our hospital were analyzed to obtain the incidence of anemia. Univariate analysis and multivariate logistic regression analysis were used to search for risk factors linked to the occurrence of anemia. Results Incidence of anemia was 72.2% in early breast cancer patients undergoing chemotherapy. The occur-rence of anemia was related to 5 risk factors: chemotherapy regiments, Hb at baseline 60 years old, BMI ≤ 25 kg/m2 and HBV antigen positive. Conclusion The anemia incidence during chemothera-py is high in early breast cancer patients. Such factors,as chemotherapy regiments, Hb at baseline, age, BMI and HBV antigen, should be taken into account in identifying high risk patients and prevent anemia.
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Axillary interventions, represented by axillary lymph node dissection (ALND), has been a key component in radical surgeries for breast cancer since the proposal of radical mastectomy. ALND substantially affects the quality of life of the patients. In recent years, many studies suggested that axillary interventions may not be necessary for all breast cancer patients, and for early early-stage patients, it brings more harm than benefit. Sentinel lymph node biopsy (SLNB) has provided good guidance to indicate the necessity of ALND, but several studies revealed that not all patients with positive SLNB results benefited from ALND. In this review, the authors summarize the recent progress of researches of these two hot issues.
Subject(s)
Female , Humans , Axilla , Breast Neoplasms , General Surgery , Lymph Node Excision , Lymph Nodes , Quality of Life , Sentinel Lymph Node BiopsyABSTRACT
<p><b>OBJECTIVE</b>To screen differentially expressed genes and identify potential signaling pathway in Asian people with breast cancer.</p><p><b>METHODS</b>Five gene microarray datasets of Asian people with breast cancer, GSE6367, GSE9309, GSE15852, GSE33447 and GSE45255, were downloaded from GEO. Microarrays with 318 breast cancer and 60 normal breast tissues were used for analysis of differentially expressed genes and pathway. 32 pairs of breast cancer patients' specimens were used to validate the differentially expressed genes by real-time PCR.</p><p><b>RESULTS</b>Analysis of the large sample of microarray data identified 436 differentially expressed genes in breast cancer tissues, while 259 of these genes were up-regulated and the other 177 down-regulated. Pathway analysis showed that metabolism-related signaling pathway may be involved in the development of breast cancer in Asian people. The expressions of KRT19, ADIPOQ, CFD, RBP4, LPL, ABCA8 and CD36 genes were confirmed by real-time PCR.</p><p><b>CONCLUSION</b>This study shows differential gene expression profile and potential signaling pathway in Asian people with breast cancer. CD36 gene may be closely related to the Asian breast cancer. ABCA8 gene may be a new disease gene in Asian breast cancer.</p>
Subject(s)
Female , Humans , Asian People , Breast Neoplasms , Genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Oligonucleotide Array Sequence Analysis , Real-Time Polymerase Chain Reaction , Signal Transduction , TranscriptomeABSTRACT
Objective:This study aimed to establish a mouse model of breast cancer by inoculating human breast cancer cells into mice with normal immune function. Methods:Forty female BALB/C mice were randomized into four groups, with 10 mice in each group. The four groups were established according to the dosage of cyclophosphamide and prednisone, namely, the control group, low dose group, medium dose group, and high dose group. The mouse models of breast cancer were established by injecting human breast cancer cells into the fat pad of the right second breast of mice in the groups. Mice in the four groups were observed based on the time of tumorigenesis, rate of tumor formation, tumor imaging and pathological features, and metastasis of vital internal organs. Results:In the high dose group, the time of tumor formation was lower than that of the other groups, but the rate of tumor formation was high. Some visceral metastases occurred in the mice. By contrast, the medium dose group revealed completely opposite results. No death and tumor formation in both the control and low dose groups were reported. Conclusion:A human breast carcinoma model in mice was successfully established. Using this model, the onset and development of breast cancer could be much better imitated in the normal immune system of mice.
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Objective To investigate the diagnose and therapy of patients with smooth muscle tumors (SMTs) of gstrointestinal tract (GI). Methods A retrospective analysis was made on the clinical and pathological data of 92 patients with SMTs of GI admitted from 1982 to 1999 in Nanfang Hospital. Results Location of the lesion: 41 cases in stomach, 44 in small intestine, and 7 in large bowel. Adjuvant examinations: BUS was performed on 63 cases with positive findings in 31; CT on 27 cases with positive findings in 20; DSA on 29 cases with positive findings in 27; barium series on 45 with positive findings in 28; and small intestinoscopy on 11 cases with pasitive findings in 2. Conclusions DSA is the most effective method in diagnoses of SMTs of GI, especially for small intestinal leiomyoma. The primary treatment of GI-SMTs is surgical resection.