Search results for "Human epidermal growth factor"
showing 10 items of 15 documents
Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion
2019
Background: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. Methods: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. Th…
The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial
2021
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes1. Additional sources of breast cancer heterogeneity may raise during the disease course. In BC patients whose disease was initially diagnosed in the early stage and subsequently progressed with metastatic involvement of one single or multiple site/s, the molecular characteristics of metastatic lesions do not necessary mimic those of the disease initially diagnosed. A well-depicted molecular landscape is crucial for subtype definition, prognostic evalu…
Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and pac…
2018
Summary Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (8…
Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives
2017
Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”,…
A first-in-human trial of RG7116, a glycoengineered monoclonal antibody targeting HER3, in patients with advanced/metastatic tumors of epithelial cel…
2013
2522 Background: The Human Epidermal Growth Factor Receptor 3 (HER3) is a key heterodimerization partner for other HER family members thereby acting as a downstream signal amplifier. This is a first in human study evaluating the safety of RG7116, a humanized anti-HER3 monoclonal antibody with potent HER3 signal inhibition. Due to a glycoengineered Fc-part this antibody displays enhanced antibody-dependent cellular cytotoxicity as compared to conventional antibodies. Methods: Patients (pts) with advanced or metastatic carcinomas with centrally confirmed HER3 protein expression were included. A “3+3” dose escalation design was performed starting at 100 mg flat dosing in a q2w regimen. In add…
A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced o…
2019
Purpose This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity. Patients and methods This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m 2) administered intravenously on a every 3-week schedule. Adverse event (A…
Place de l’imagerie dans l’évaluation de l’efficacité des traitements dans le cancer du sein
2010
Resume Cette revue decrit le role de differentes methodes d’imagerie pour evaluer la reponse au traitement dans le cancer du sein. Deux situations sont envisageables : celle de la chimiotherapie neoadjuvante du cancer du sein et celle des metastases. Beaucoup de donnees cliniques sont disponibles pour trois criteres : le volume de la tumeur, la captation du fluorodeoxyglucose mesuree en TEP et la perfusion de la tumeur evaluee soit par IRM dynamique, soit en TEP. La TEP au 2-18F fluoro-2-desoxy-D-glucose (FDG) permet la prediction de la reponse apres une ou deux cures de chimiotherapie. De nouvelles approches pourraient prochainement affiner le role de l’imagerie. Ainsi, la TEP a la thymidi…
Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast canc…
2021
Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28–8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers. The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with th…
The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population
2013
<b><i>Background:</i></b> Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. <b><i>Patients and Methods:</i></b> Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). <b><i>Results:<…
Letter to the Editor regarding the paper by Aurilio et al., A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth f…
2014
Sir,We have read with great interest the article in press ofAurilio et al., A meta-analysis of oestrogen receptor, pro-gesterone receptor and human epidermal growth factorreceptor 2 discordance between primary breast cancerand metastases (http://dx.doi.org/10.1016/j.ejca.2003.10.004), which will appear in Eur J Cancer. In the paper,the Authors have performed a meta-analysis of the stud-ies published in the literature concerning the discor-dance rate in oestrogen receptor (ER), progesteronereceptor (PgR) and HER2 status between primarytumour and corresponding relapse. It is well known thata considerable controversy concerns the issue of hor-mone receptors (HRs) expression as well as HER2 sta…