scholarly journals Livin participates in resistance to trastuzumab therapy for breast cancer through ERK1/2 and AKT pathways and promotes EMT-like phenotype

RSC Advances ◽  
2018 ◽  
Vol 8 (50) ◽  
pp. 28588-28601 ◽  
Author(s):  
Fan Li ◽  
Lu Zhang ◽  
Fan Feng ◽  
Ke Zheng ◽  
YuJing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Trastuzumab Resistance ◽  
Human Epidermal Growth Factor ◽  
Trastuzumab Therapy ◽  
Epidermal Growth

Trastuzumab resistance has emerged as a major issue in anti-human epidermal growth factor receptor-2 (HER2) therapy for breast cancers.

scholarly journals Weekly Trastuzumab Therapy Cannot Prevent Severe Trastuzumab-induced Thrombocytopenia: A Case Report

2020 ◽  
Author(s):  
Xin Wang ◽  
Xiaoli Zhu ◽  
Jieya Zou ◽  
Xia Zhang ◽  
Xuemei Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
The Body ◽  
Severe Thrombocytopenia ◽  
Human Epidermal Growth Factor ◽  
Trastuzumab Therapy ◽  
Epidermal Growth

Abstract Background: Trastuzumab can significantly prolong the survival of patients with positive human epidermal growth factor receptor-2 breast cancer. Until now, trastuzumab has been used by millions of people, and trastuzumab-induced thrombocytopenia is rare. There is no report of acute grade 4 thrombocytopenia after weekly trastuzumab therapy. We report a breast cancer patient with severe thrombocytopenia due to trastuzumab (8mg/Kg) who experienced a recurrence of severe thrombocytopenia after attempting weekly trastuzumab therapy (4mg/Kg). Case presentation：A 52-year-old woman with positive human epidermal growth factor receptor-2 breast cancer developed acicular rash with dense skin all over the body and gingival bleeding within 24 hours of trastuzumab infusion (8mg/Kg) and was confirmed to have severe thrombocytopenia, which was quickly recovered after high-dose corticosteroid pulse therapy. When the platelet count recovered, we tried weekly trastuzumab therapy (4mg/kg), Unfortunately, thrombocytopenia recurred within 24 hours. No third trastuzumab treatment was attempted. Conclusion: We are the first report to try weekly trastuzumab therapy after thrombocytopenia induced by first trastuzumab. The patient showed that reducing the dose of trastuzumab was ineffective in preventing trastuzumab-induced thrombocytopenia.

scholarly journals Advances in therapy of breast cancer: overexpression and therapeutic implications of targeting human epidermal growth factor receptors

2019 ◽  
Vol 8 (5) ◽  
pp. 1126
Author(s):  
Amit Bhalla
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
Receptor Family

The human epidermal growth factor receptor 2 (HER2) ERbb2 gene is amplified in approximately 25% of breast cancers. Characteristics of HER2-amplified tumors include increased proliferation rates and a propensity for distant metastasis. The discovery of overexpression of HER2 in a subset of breast cancers was an important milestone in our understanding of the biology of the disease. This paved the way for the discovery of trastuzumab, a humanized monoclonal antibody targeting HER2. Trastuzumab is the foundation of treatment of HER2- positive breast cancers, demonstrating dramatic responses in patients with metastatic disease. Recent advances in our understanding of the interaction between HER2 and other members of the epidermal growth factor receptor family have led to the identification of newer agents, resulting in the expansion of the clinical armamentarium of available agents for the treatment of HER2-positive tumors. The biology of the ERbb receptor family, the use of HER2-targeted agents in breast cancer, and the advances in anti-HER2 agents that are currently in clinical development are reviewed here.

scholarly journals Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e035802
Author(s):  
Qiancheng Hu ◽  
Xin Wang ◽  
Ye Chen ◽  
Xiaofen Li ◽  
Ting Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Early Breast Cancer ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.Methods and analysisElectronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.Ethics and disseminationEthics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.Trial registration numberCRD42019139109.

scholarly journals Loss of Phosphatase and Tensin Homolog or Phosphoinositol-3 Kinase Activation and Response to Trastuzumab or Lapatinib in Human Epidermal Growth Factor Receptor 2–Overexpressing Locally Advanced Breast Cancers

2011 ◽  
Vol 29 (2) ◽  
pp. 166-173 ◽  
Author(s):  
Bhuvanesh Dave ◽  
Ilenia Migliaccio ◽  
M. Carolina Gutierrez ◽  
Meng-Fen Wu ◽  
Gary C. Chamness ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Trastuzumab Resistance ◽  
Epidermal Growth

Purpose Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be associated with trastuzumab resistance. Trastuzumab, the humanized human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and lapatinib, an epidermal growth factor receptor/HER2 tyrosine kinase inhibitor, are both established treatments for HER2-overexpressing breast cancers. Understanding of the cellular response to HER2-targeted therapies is needed to tailor treatments and to identify patients less likely to benefit. Methods We evaluated the effect of trastuzumab or lapatinib in three HER2-overexpressing cell lines. We confirmed the in vitro observations in two neoadjuvant clinical trials in patients with HER2 overexpression; 35 patients received trastuzumab as a single agent for the first 3 weeks, then docetaxel every 3 weeks for 12 weeks (trastuzumab regimen), whereas 49 patients received lapatinib as a single agent for 6 weeks, followed by trastuzumab/docetaxel for 12 weeks before primary surgery (lapatinib regimen). Apoptosis, Ki67, p-MAPK, p-AKT, and PTEN were assessed by immunohistochemistry. Genomic DNA was sequenced for PIK3CA mutations. Results Under low PTEN conditions, in vitro data indicate that lapatinib alone and in combination with trastuzumab was effective in decreasing p-MAPK and p-AKT levels, whereas trastuzumab was ineffective. In the clinical trials, we confirmed that low PTEN or activating mutation in PIK3CA conferred resistance to the trastuzumab regimen (P = .015), whereas low PTEN tumors were associated with a high pathologic complete response rate (P = .007). Conclusion Activation of PI3 kinase pathway is associated with trastuzumab resistance, whereas low PTEN predicted for response to lapatinib. These observations support clinical trials with the combination of both agents.

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