ArticleOncogene2010
A novel interaction between HER2/neu and cyclin E in breast cancer.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02536742 (A Phase II Study of Palbociclib Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast Cancer), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Study of Palbociclib Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast Cancer
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Risk of severe diarrhea with dual anti-HER2 therapies: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- Cyclin E1 Expression Predicts Poorer Outcome in HER2-positive Breast Cancer with Residual Disease after Neoadjuvant Chemotherapy.Annals of surgical oncology · 2026Article
- Article
- Review
- Emerging HER2 Targeting Immunotherapy for Cholangiocarcinoma.Oncology research · 2025Review
- Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge.Cancer immunology, immunotherapy : CII · 2022Article
- Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment.Nature cancer · 2021Review
- Cyclin E overexpression confers resistance to trastuzumab through noncanonical phosphorylation of SMAD3 in HER2+ breast cancer.Cancer biology & therapy · 2020Article
- Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity.Journal of nanobiotechnology · 2020Article
- Low-Molecular-Weight Cyclin E in Human Cancer: Cellular Consequences and Opportunities for Targeted Therapies.Cancer research · 2018Review
- Targeting tumor cells with antibodies enhances anti-tumor immunity.Biophysics reports · 2018Article
- Cytoplasmic Cyclin E Mediates Resistance to Aromatase Inhibitors in Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Cytoplasmic Cyclin E Predicts Recurrence in Patients with Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Cytoplasmic Cyclin E and Phospho-Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer.The American journal of pathology · 2016Article
- Cyclin E amplification, over-expression, and relapse-free survival in HER-2-positive primary breast cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth.Oncotarget · 2016Article
- Immunohistochemical prediction of lapatinib efficacy in advanced HER2-positive breast cancer patients.Oncotarget · 2016Article
- Novel Molecular Markers for Breast Cancer.Biomarkers in cancer · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
HER2/neu (HER2) and cyclin E are important prognostic indicators in breast cancer. As both are involved in cell cycle regulation we analyzed whether there was a direct interaction between the two. HER2 and cyclin E expression levels were determined in 395 breast cancer patients. Patients with HER2-overexpression and high levels of cyclin E had decreased 5-year disease-specific survival compared with low levels of cyclin E (14% versus 89%, P<0.0001). In vitro studies were performed in which HER2-mediated activity in HER2-overexpressing breast cancer cell lines was downregulated by transfection with HER2 small interfering RNA or treatment with trastuzumab. Cyclin E expression levels were determined by western blot analysis, and functional effects analyzed using kinase assays, MTT assays were used to assess cell viability as a marker of proliferation and fluorescence-activated cell sorting analysis was used to determine cell cycle profiles. Decreased HER2-mediated signaling resulted in decreased expression of cyclin E, particularly the low molecular weight (LMW) isoforms. Decreased HER2 and LMW cyclin E expression had functional consequences, including decreased cyclin E-associated kinase activity and decreased proliferation, because of increased apoptosis and an increased accumulation of cells in the G1 phase. In vivo studies performed in a HER2-overexpressing breast cancer xenograft model confirmed the effects of trastuzumab on cyclin E expression. Given the relationship between HER2 and cyclin E, in vitro clonogenic assays were performed to assess combination therapy targeting both proteins. Isobologram analysis showed a synergistic interaction between the two agents (trastuzumab targeting HER2 and roscovitine targeting cyclin E). Taken together, these studies show that HER2-mediated signaling effects LMW cyclin E expression, which in turn deregulates the cell cycle. LMW cyclin E has prognostic and predictive roles in HER2-overexpressing breast cancer, warranting further study of its potential as a therapeutic target.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.