PMID- 18193353
OWN - NLM
STAT- MEDLINE
DCOM- 20090203
LR  - 20141120
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 112
IP  - 3
DP  - 2008 Dec
TI  - New cutpoints to identify increased HER2 copy number: analysis of a large, 
      population-based cohort with long-term follow-up.
PG  - 453-9
LID - 10.1007/s10549-007-9887-y [doi]
AB  - BACKGROUND: HER2 gene amplification and/or protein overexpression in breast 
      cancer is associated with a poor prognosis and predicts response to anti-HER2 
      therapy. We examine the natural history of breast cancers in relationship to 
      increased HER2 copy numbers in a large population-based study. PATIENTS AND 
      METHODS: HER2 status was measured by fluorescence in situ hybridization (FISH) 
      and immunohistochemistry (IHC) in approximately 1,400 breast cancer cases with 
      greater than 15 years of follow-up. Protein expression was evaluated with two 
      different commercially-available antibodies. RESULTS: We looked for subgroups of 
      breast cancer with different clinical outcomes, based on HER2 FISH amplification 
      ratio. The current HER2 ratio cut point for classifying HER2 positive and 
      negative cases is 2.2. However, we found an increased risk of disease-specific 
      death associated with FISH ratios of >1.5. An 'intermediate' group of cases with 
      HER2 ratios between 1.5 and 2.2 was found to have a significantly better outcome 
      than the conventional 'amplified' group (HER2 ratio >2.2) but a significantly 
      worse outcome than groups with FISH ratios less than 1.5. CONCLUSION: Breast 
      cancers with increased HER2 copy numbers (low level HER2 amplification), below 
      the currently accepted positive threshold ratio of 2.2, showed a distinct, 
      intermediate outcome when compared to HER2 unamplified tumors and tumors with 
      HER2 ratios greater than 2.2. These findings suggest that a new cut point to 
      determine HER2 positivity, at a ratio of 1.5 (well below the current recommended 
      cut point of 2.2), should be evaluated.
FAU - Jensen, K C
AU  - Jensen KC
AD  - Stanford University, Stanford, CA 94305, USA. kjensen1@stanford.edu
FAU - Turbin, D A
AU  - Turbin DA
FAU - Leung, S
AU  - Leung S
FAU - Miller, M A
AU  - Miller MA
FAU - Johnson, K
AU  - Johnson K
FAU - Norris, B
AU  - Norris B
FAU - Hastie, T
AU  - Hastie T
FAU - McKinney, S
AU  - McKinney S
FAU - Nielsen, T O
AU  - Nielsen TO
FAU - Huntsman, D G
AU  - Huntsman DG
FAU - Gilks, C B
AU  - Gilks CB
FAU - West, R B
AU  - West RB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080109
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/genetics/metabolism
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Amplification
MH  - *Genes, erbB-2
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Multivariate Analysis
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Receptor, ErbB-2/biosynthesis/*genetics/physiology
MH  - Receptors, Estrogen/metabolism
MH  - Treatment Outcome
EDAT- 2008/01/15 09:00
MHDA- 2009/02/04 09:00
CRDT- 2008/01/15 09:00
PHST- 2007/12/24 00:00 [received]
PHST- 2007/12/27 00:00 [accepted]
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2009/02/04 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - 10.1007/s10549-007-9887-y [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2008 Dec;112(3):453-9. doi: 10.1007/s10549-007-9887-y. 
      Epub 2008 Jan 9.