PMID- 21901388
OWN - NLM
STAT- MEDLINE
DCOM- 20120820
LR  - 20141120
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 133
IP  - 1
DP  - 2012 May
TI  - Genetic heterogeneity in HER2 testing may influence therapy eligibility.
PG  - 161-8
LID - 10.1007/s10549-011-1744-3 [doi]
AB  - Prospective studies have demonstrated that approximately 20% of HER2 testing may 
      be inaccurate. When carefully validated testing is conducted, available data do 
      not clearly demonstrate the superiority of either IHC or fluorescence in situ 
      hybridization (FISH) as a predictor of benefit from anti-HER2 therapy. In 
      addition, the interpretation of the findings of HER2 tests according to 
      international guidelines is not uniform. The American Society of Clinical 
      Oncology (ASCO) and the College of American Pathologists (CAP) recently published 
      practice guidelines for a definition of HER2 amplification heterogeneity that can 
      give rise to discrepant results between IHC and FISH assays for HER2. In this 
      article, we compare the HER2 status of 291 non consecutive breast cancers. The 
      status is determined by both IHC and FISH approaches, using a specific FISH 
      strategy to investigate genetic heterogeneity. Our data demonstrate that HER2 
      amplified cells may be found as diffuse, clustered in a specific area or section, 
      intermingled with non-amplified cells or confined to metastatic nodules. The 
      correct evaluation of ratio value in the presence of genetic heterogeneity and of 
      polysomy contributes to the accurate assessment of HER2 status and potentially 
      affects the selection of appropriate anti-HER2 therapy. By taking into account 
      the presence of different genetic cell populations, the immunotherapy eligibility 
      criteria for HER2 FISH scoring proposed in the CAP (2009) and SIGU guidelines 
      identify an additional subset of cases for trastuzumab or lapatinib therapy 
      compared to the ASCO/CAP (2007) guidelines.
FAU - Bernasconi, Barbara
AU  - Bernasconi B
AD  - Department of Human Morphology, Section of Anatomic Pathology, University of 
      Insubria and Ospedale di Circolo, Via O. Rossi, 9, 21100 Varese, Italy. 
      barbara1.bernasconi@uninsubria.it
FAU - Chiaravalli, Anna Maria
AU  - Chiaravalli AM
FAU - Finzi, Giovanna
AU  - Finzi G
FAU - Milani, Katia
AU  - Milani K
FAU - Tibiletti, Maria Grazia
AU  - Tibiletti MG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20110908
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/drug therapy/*genetics
MH  - Breast Neoplasms, Male/drug therapy/*genetics
MH  - Carcinoma, Ductal, Breast/drug therapy/*genetics
MH  - Female
MH  - Gene Amplification
MH  - *Genetic Heterogeneity
MH  - *Genetic Testing
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Neoplasms, Hormone-Dependent/drug therapy/*genetics
MH  - Practice Guidelines as Topic
MH  - Receptor, ErbB-2/*genetics
EDAT- 2011/09/09 06:00
MHDA- 2012/08/21 06:00
CRDT- 2011/09/09 06:00
PHST- 2011/04/27 00:00 [received]
PHST- 2011/08/16 00:00 [accepted]
PHST- 2011/09/09 06:00 [entrez]
PHST- 2011/09/09 06:00 [pubmed]
PHST- 2012/08/21 06:00 [medline]
AID - 10.1007/s10549-011-1744-3 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 May;133(1):161-8. doi: 10.1007/s10549-011-1744-3. 
      Epub 2011 Sep 8.