PMID- 16133791
OWN - NLM
STAT- MEDLINE
DCOM- 20060302
LR  - 20220801
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 23
IP  - 5
DP  - 2005 Oct
TI  - Anti-erbB-2 antibody trastuzumab in the treatment of HER2-amplified breast 
      cancer.
PG  - 391-409
AB  - Human epidermal growth factor receptor-2 (HER2/erbB-2) is a member of a family of 
      four transmembrane receptor tyrosine kinases that regulate cell growth, survival 
      and differentiation via multiple signal transduction pathways. Amplification of 
      the HER2 gene occurs in 20-25% of human breast cancers. This amplification event 
      is an independent adverse prognostic factor as well as a predictive factor for 
      increased response to doxorubicin-based combination chemotherapy, response to 
      trastuzumab and decreased response to hormonal therapy. Methods for detecting 
      protein overexpression or gene amplification in clinical tumor specimens include 
      immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) 
      techniques, with the latter considered by some to be more accurate. Trastuzumab 
      (Herceptin) is a recombinant humanized monoclonal antibody which targets an 
      epitope in the extracellular domain of the HER2 protein. Preclinical models 
      demonstrated that this antibody has significant anti-tumor activity as a single 
      agent and has synergy with certain chemotherapeutic drugs. Phase II and III 
      clinical trials performed in women with metastatic breast cancer that overexpress 
      HER2 have shown that trastuzumab has clinical activity when used as first-, 
      second- or third-line monotherapy, and improves survival when used as first-line 
      therapy in combination with chemotherapy. Newer combinations with numerous 
      chemotherapeutic drugs have also shown significant clinical activity in phase II 
      studies. In all of these trials, trastuzumab was generally well-tolerated, but 
      cardiac toxicity (particularly when the antibody was combined with 
      anthracyclines) was an unexpected adverse effect. Although trastuzumab is 
      currently usually administered on a weekly intravenous schedule, evidence 
      suggests that a triple dose of the drug given once every three weeks has a 
      pharmacokinetic profile expected to be equally efficacious. Neither the optimal 
      schedule nor the optimal duration of trastuzumab therapy has yet been clearly 
      defined in controlled clinical trials. Current clinical investigations of 
      trastuzumab include its use in both the adjuvant and neoadjuvant settings as well 
      as in combination with other chemotherapy drugs or new biologic targeted agents.
FAU - Yeon, Christina H
AU  - Yeon CH
AD  - Division of Hematology-Oncology and the Jonsson Comprehensive Cancer Center, 
      University of California, Los Angeles, CA, USA. christina.yeon@womgi.com
FAU - Pegram, Mark D
AU  - Pegram MD
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy
MH  - Clinical Trials as Topic
MH  - Female
MH  - Heart/drug effects/physiology
MH  - Humans
MH  - Receptor, ErbB-2/*immunology/metabolism
MH  - Trastuzumab
RF  - 131
EDAT- 2005/09/01 09:00
MHDA- 2006/03/03 09:00
CRDT- 2005/09/01 09:00
PHST- 2005/09/01 09:00 [pubmed]
PHST- 2006/03/03 09:00 [medline]
PHST- 2005/09/01 09:00 [entrez]
AID - 10.1007/s10637-005-2899-8 [doi]
PST - ppublish
SO  - Invest New Drugs. 2005 Oct;23(5):391-409. doi: 10.1007/s10637-005-2899-8.