PMID- 16754938
OWN - NLM
STAT- MEDLINE
DCOM- 20060719
LR  - 20181201
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 24
IP  - 19
DP  - 2006 Jul 1
TI  - Estrogen-independent proliferation is present in estrogen-receptor HER2-positive 
      primary breast cancer after neoadjuvant letrozole.
PG  - 3019-25
AB  - PURPOSE: To investigate the impact of human epidermal growth factor receptor 
      (HER) 1 and HER2 gene amplification on endocrine therapy responsiveness, a 
      fluorescence in situ hybridization (FISH) study was conducted on tumor samples 
      from 305 postmenopausal patients with stage II and III estrogen receptor (ER) 
      -positive (ER > or = 10%) breast cancers treated on two independent neoadjuvant 
      endocrine therapy trials. PATIENTS AND METHODS: FISH analysis focused on HER1 
      and/or HER2 immunohistochemistry (IHC) -positive patients and a random selection 
      of HER1/2 IHC-negative patients. HER2 FISH status was correlated with response 
      and changes in the proliferation marker Ki67. RESULTS: HER1 was rarely amplified 
      (< 1%), and HER2 amplification was observed in 9.2% of patients. Letrozole 
      response by clinical measurement (71% HER2 FISH positive v 71% HER2 FISH 
      negative), mammogram (44% HER2 FISH positive v 47% HER2 FISH negative), or 
      ultrasound (47% HER2 FISH positive v 54% HER2 FISH negative) was not impaired by 
      HER2 FISH-positive status. In contrast, HER2 FISH-positive tumors showed higher 
      histologic grade (P = .009), higher pretreatment Ki67 (P = .005), and less Ki67 
      suppression after letrozole when compared with HER2 FISH-negative tumors (P = 
      .0001). Similar observations regarding Ki67 were made in a smaller cohort of 
      tamoxifen-treated tumors. CONCLUSION: Neoadjuvant letrozole is clinically 
      effective in ER-positive HER2 FISH-positive tumors, indicating sensitivity to 
      short-term estrogen deprivation. However, continued proliferation despite ongoing 
      letrozole or tamoxifen treatment in the majority of ER-positive HER2 
      FISH-positive samples (88%) could imply therapeutic resistance that may manifest 
      later in the clinical course of the disease. Discordance between clinical and 
      biomarker findings in this study serves to emphasize the need for surrogate end 
      point validation in neoadjuvant endocrine trials through correlation with 
      information on long-term outcomes.
FAU - Ellis, Matthew J
AU  - Ellis MJ
AD  - Siteman Comprehensive Cancer Center,, Washington University School of Medicine, 
      Campus Box 8056, 660 S Euclid Ave, St Louis, MO 63110, USA. mellis@wustl.edu
FAU - Tao, Yu
AU  - Tao Y
FAU - Young, Oliver
AU  - Young O
FAU - White, Sharon
AU  - White S
FAU - Proia, Alan D
AU  - Proia AD
FAU - Murray, Julliette
AU  - Murray J
FAU - Renshaw, Lorna
AU  - Renshaw L
FAU - Faratian, Dana
AU  - Faratian D
FAU - Thomas, Jeremy
AU  - Thomas J
FAU - Dowsett, Mitch
AU  - Dowsett M
FAU - Krause, Andreas
AU  - Krause A
FAU - Evans, Dean B
AU  - Evans DB
FAU - Miller, William R
AU  - Miller WR
FAU - Dixon, J Michael
AU  - Dixon JM
LA  - eng
GR  - CA0961402/CA/NCI NIH HHS/United States
GR  - P30CA9184205/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060605
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Nitriles)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Triazoles)
RN  - 7LKK855W8I (Letrozole)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Biomarkers, Tumor/analysis
MH  - Breast Neoplasms/*drug therapy/*physiopathology
MH  - Cell Proliferation/*drug effects
MH  - Female
MH  - Gene Amplification
MH  - Genes, erbB-1
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Letrozole
MH  - Middle Aged
MH  - Neoadjuvant Therapy
MH  - Nitriles/*therapeutic use
MH  - Receptor, ErbB-2/*genetics
MH  - Receptors, Estrogen/analysis
MH  - Treatment Outcome
MH  - Triazoles/*therapeutic use
EDAT- 2006/06/07 09:00
MHDA- 2006/07/20 09:00
CRDT- 2006/06/07 09:00
PHST- 2006/06/07 09:00 [pubmed]
PHST- 2006/07/20 09:00 [medline]
PHST- 2006/06/07 09:00 [entrez]
AID - JCO.2005.04.3034 [pii]
AID - 10.1200/JCO.2005.04.3034 [doi]
PST - ppublish
SO  - J Clin Oncol. 2006 Jul 1;24(19):3019-25. doi: 10.1200/JCO.2005.04.3034. Epub 2006 
      Jun 5.