scholarly journals Cardiotoxicity among Patients Using Pertuzumab, Trastuzumab and Taxane with HER2-Positive Early-Stage Breast Cancer: A Single-Centre Experience

2021 ◽  
pp. 465-474
Author(s):  
Alanood S. Algarni ◽  
Anan A. Alfi ◽  
Azuf T. Turkistani ◽  
Layal E. Malki ◽  
Nouf F. Alghanam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ejection Fraction ◽  
Drug Combination ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Aim: In this study, we aimed to investigate the incidence rate, risk factors, and mortality rates in patients with early-stage breast cancer using anti-HER2 (Human epidermal growth factor receptor-2) treatment. Patients and Methods: A total of 106 patients diagnosed with human epidermal growth factor 2 (HER2)-positive early-stage breast cancer and receiving anti-HER2 treatment at King Abdulaziz Medical City (KAMC) from 2015 to 2019 were included in the analysis to assess the incidence of cardiotoxicity was collected as a retrospective study. Univariate and multivariate analyses as well as multiple exact logistic regression analysis were conducted to understand the relationships between the left ventricular ejection fraction (LVEF) and treatment combinations and comorbidities Results: The LVEF measurements using an echocardiography method at the baseline (before any treatment) and during the anti-HER2 therapy were assessed. The results suggest that the higher the drug combination, the higher the odds ratio for the declined ejection fraction (EF) patient group. Further, patients treated with the pertuzumab and trastuzumab combination were four times more likely to have a decline in their EF than those who did not use the pertuzumab and trastuzumab drug combination (OR 4.28, 95% CI [1.68–10.91]). Conclusion: This study demonstrated that the drug combination considered here is associated with reduced LVEF and, similarly, comorbidities were also related to EF. However, a larger study in a global patient population will confirm the present observations.

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.

Exploring mechanisms of acquired resistance to HER2 (human epidermal growth factor receptor 2)-targeted therapies in breast cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 822-830 ◽  
Author(s):  
Helen Creedon ◽  
Adam Byron ◽  
Joanna Main ◽  
Larry Hayward ◽  
Teresa Klinowska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

HER2 (human epidermal growth factor receptor 2)-targeted therapy in breast cancer is one of the earliest and arguably most successful examples of the modern class of targeted drugs. Initially identified in the 1980s, the observation that HER2 acts as an independent predictor of poor prognosis in the 20% of breast cancer cases carrying a gene amplification or protein overexpression cemented its place at the forefront of research in this field. The outlook for patients with HER2-positive breast cancer has been revolutionized by the introduction of HER2-targeted agents, such as trastuzumab and lapatinib, yet resistance is frequently encountered and multiple different resistance mechanisms have been identified. We have explored resistance to a novel pan-HER inhibitor, AZD8931, and we examine mechanisms of resistance common to trastuzumab, lapatinib and AZD8931, and discuss the current problems associated with translating the wealth of pre-clinical data into clinical benefit.

scholarly journals Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 737 ◽  
Author(s):  
Denis M. Collins ◽  
Neil T. Conlon ◽  
Srinivasaraghavan Kannan ◽  
Chandra S. Verma ◽  
Lisa D. Eli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Epidermal Growth

An estimated 15–20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2/ERBB2/neu). Two small-molecule tyrosine kinase inhibitors (TKIs), lapatinib and neratinib, have been approved for the treatment of HER2-positive (HER2+) breast cancer. Lapatinib, a reversible epidermal growth factor receptor (EGFR/ERBB1/HER1) and HER2 TKI, is used for the treatment of advanced HER2+ breast cancer in combination with capecitabine, in combination with trastuzumab in patients with hormone receptor-negative metastatic breast cancer, and in combination with an aromatase inhibitor for the first-line treatment of HER2+ breast cancer. Neratinib, a next-generation, irreversible pan-HER TKI, is used in the US for extended adjuvant treatment of adult patients with early-stage HER2+ breast cancer following 1 year of trastuzumab. In Europe, neratinib is used in the extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2+ breast cancer who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy. Preclinical studies have shown that these agents have distinct properties that may impact their clinical activity. This review describes the preclinical characterization of lapatinib and neratinib, with a focus on the differences between these two agents that may have implications for patient management.

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