Document Detail


Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ.
MedLine Citation:
PMID:  25186428     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS.
METHODS: Patients with HER2 positive DCIS received 1,500 mg daily of lapatinib for four consecutive weeks prior to surgical resection. Magnetic resonance imaging (MRI) was used to determine changes in tumor volume. The molecular effects of lapatinib on HER2 signaling (PI3K/AKT and RAS/MAPK pathways), cell proliferation (Ki67 and p27) and apoptosis (TUNEL) were determined in pre and post-lapatinib treatment samples.
RESULTS: A total of 20 patients were included. Lapatinib was well tolerated with only minor and transient side effects. The agent effectively modulated HER2 signaling decreasing significantly pHER2 and pERK1 expression, together with a decrease in tumor size evaluated by MRI. There was no evidence of changes in Ki67.
CONCLUSIONS: Four weeks of neoadjuvant lapatinib in patients with HER2-positive DCIS resulted in inhibition of HER2 and RAS/MAPK signaling pathway.Trial registration: 2008-004492-21 (Registered June 25th 2008).
Authors:
Laura G Estévez; Ana Suarez-Gauthier; Elena García; Cristina Miró; Isabel Calvo; María Fernández-Abad; Mercedes Herrero; Manuel Marcos; Cristina Márquez; Fernando Lopez Ríos; Sofía Perea; Manuel Hidalgo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-4
Journal Detail:
Title:  Breast cancer research : BCR     Volume:  16     ISSN:  1465-542X     ISO Abbreviation:  Breast Cancer Res.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100927353     Medline TA:  Breast Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  R76     Citation Subset:  -    
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