PMID- 19364966
OWN - NLM
STAT- MEDLINE
DCOM- 20090709
LR  - 20220318
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 18
DP  - 2009 Jun 20
TI  - Disease-free survival according to degree of HER2 amplification for patients 
      treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the 
      HERA Trial.
PG  - 2962-9
LID - 10.1200/JCO.2008.19.7939 [doi]
AB  - PURPOSE: To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ 
      or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification 
      according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy 
      significantly influenced clinical outcome for patients with human epidermal 
      growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin 
      Adjuvant trial of trastuzumab versus no trastuzumab administered after completion 
      of chemotherapy. PATIENTS AND METHODS: IHC and/or FISH analyses were performed 
      locally and required central confirmation as indicating HER2 positivity for trial 
      entry. FISH data from the central HER2 analysis on patients in the 1-year 
      trastuzumab and no trastuzumab arms were assessed in relation to disease-free 
      survival (DFS) after a median 2 years of follow-up. RESULTS: Central FISH results 
      were available for 2,071 (61%) of the 3,401 patients randomized to the 2 arms. 
      Among patients with FISH-positive disease, (1) the hazard ratios for trastuzumab 
      versus no trastuzumab were 0.56 (95% CI, 0.32 to 0.99) for locally IHC2+ cases (n 
      = 340) and 0.80 (95% CI, 0.40 to 1.61) for centrally IHC2+ cases (n = 299). There 
      was no significant prognostic relationship between (2a) HER2 FISH ratio, (2b) 
      HER2 copy number, or (3) polysomy and DFS in the control arm or predictive 
      relationship defining differential benefit from trastuzumab. CONCLUSION: There 
      was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases. The 
      degree of HER2 amplification does not influence prognosis or benefit from 
      adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy.
FAU - Dowsett, Mitch
AU  - Dowsett M
AD  - Department of Academic Biochemistry, Royal Marsden Hospital, London, UK. 
      mitch.dowsett@icr.ac.uk
FAU - Procter, Marion
AU  - Procter M
FAU - McCaskill-Stevens, Worta
AU  - McCaskill-Stevens W
FAU - de Azambuja, Evandro
AU  - de Azambuja E
FAU - Dafni, Urania
AU  - Dafni U
FAU - Rueschoff, Josef
AU  - Rueschoff J
FAU - Jordan, Bruce
AU  - Jordan B
FAU - Dolci, Stella
AU  - Dolci S
FAU - Abramovitz, Mark
AU  - Abramovitz M
FAU - Stoss, Oliver
AU  - Stoss O
FAU - Viale, Giuseppe
AU  - Viale G
FAU - Gelber, Richard D
AU  - Gelber RD
FAU - Piccart-Gebhart, Martine
AU  - Piccart-Gebhart M
FAU - Leyland-Jones, Brian
AU  - Leyland-Jones B
LA  - eng
GR  - BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090413
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 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/genetics/mortality
MH  - Disease-Free Survival
MH  - Female
MH  - *Gene Amplification
MH  - *Genes, erbB-2
MH  - Humans
MH  - Immunohistochemistry
MH  - Prognosis
MH  - Trastuzumab
PMC - PMC2701645
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2009/04/15 09:00
MHDA- 2009/07/10 09:00
PMCR- 2010/06/20
CRDT- 2009/04/15 09:00
PHST- 2009/04/15 09:00 [entrez]
PHST- 2009/04/15 09:00 [pubmed]
PHST- 2009/07/10 09:00 [medline]
PHST- 2010/06/20 00:00 [pmc-release]
AID - JCO.2008.19.7939 [pii]
AID - 97939 [pii]
AID - 10.1200/JCO.2008.19.7939 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Jun 20;27(18):2962-9. doi: 10.1200/JCO.2008.19.7939. Epub 2009 
      Apr 13.