HER2 Support Group Forums - View Single Post - her2 copy number cut-off point (by FISH) may be decreased (2.2to1.5)

Lani · 03-25-2009, 10:21 PM

Titre du document / Document title
New cutpoints to identify increased HER2 copy number : analysis of a large, population-based cohort with long-term follow-up
Auteur(s) / Author(s)
JENSEN K. C. (1) ; TURBIN D. A. (2) ; LEUNG S. (2) ; MILLER M. A. (2) ; JOHNSON K. (2) ; NORRIS B. (2) ; HASTIE T. (3) ; MCKINNEY S. (2) ; NIELSEN T. O. (2) ; HUNTSMAN D. G. (2) ; GILKS C. B. (2) ; WEST R. B. (3) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, ETATS-UNIS
(2) Genetic Pathology Evaluation Centre of the Vancouver Coastal Research Institute, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, CANADA
(3) Stanford University, Room L235, 300 Pasteur Drive, Stanford, CA 94305, ETATS-UNIS
RÃ©sumÃ© / Abstract
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.
Revue / Journal Title
Breast cancer research and treatment ISSN 0167-6806 CODEN BCTRD6
Source / Source
2008, vol. 112, no3, pp. 453-459 [7 page(s) (article)] (33 ref.)
Langue / Language
Anglais
Editeur / Publisher
Springer, Dordrecht, PAYS-BAS (1981) (Revue)
Mots-clÃ©s anglais / English Keywords
Anatomic pathology ; Breast disease ; Mammary gland diseases ; Cancer ; Malignant tumor ; Human Epidermal growth factor Receptor 2 ; Survival ; Immunohistochemistry ; Gene overexpression ; Gene amplification ; Fluorescence in situ hybridization ; Breast cancer ; Follow up study ; Long term ; Cohort study ; Public health ; Analysis ; Copy number ; erbB2 Gene ; Protooncogene ; C-Onc gene ;
Mots-clÃ©s franÃ§ais / French Keywords
Anatomopathologie ; Pathologie du sein ; Pathologie de la glande mammaire ; Cancer ; Tumeur maligne ; RÃ©cepteur HER2 ; Survie ; Immunohistochimie ; Surexpression gÃ©nique ; Amplification gÃ©nique ; Hybridation in situ fluorescence ; Cancer du sein ; Etude longitudinale ; Long terme ; Etude cohorte ; SantÃ© publique ; Analyse ; Nombre copie ; GÃ¨ne erbB2 ; ProtooncogÃ¨ne ; GÃ¨ne onc cellulaire ;
Mots-clÃ©s espagnols / Spanish Keywords
AnatomÃ*a patolÃ³gica ; Seno patologÃ*a ; GlÃ¡ndula mamaria patologÃ*a ; CÃ¡ncer ; Tumor maligno ; Sobrevivencia ; InmunohistoquÃ*mica ; SobreexpresiÃ³n genÃ©tica ; AmplificaciÃ³n gÃ©nica ; HibridaciÃ³n in situ fluorescencia ; CÃ¡ncer del pecho ; Estudio longitudinal ; Largo plazo ; Estudio cohorte ; Salud pÃºblica ; AnÃ¡lisis ; NÃºmero copia ; Gen erbB2 ; Protooncogen ; Gen onc celular ;
Mots-clÃ©s d'auteur / Author Keywords
Breast cancer . Fluorescence in situ hybridization . HER2 amplification . Her2 overexpression ; Immunohistochemistry . Survival ;
Localisation / Location
INIST-CNRS, Cote INIST : 20699, 35400018402348.0070

NÂº notice refdoc (ud4) : 20901940

03-25-2009, 10:21 PM	#4
Lani Senior Member Join Date: Mar 2006 Posts: 4,783	it is from 2008 Titre du document / Document title New cutpoints to identify increased HER2 copy number : analysis of a large, population-based cohort with long-term follow-up Auteur(s) / Author(s) JENSEN K. C. (1) ; TURBIN D. A. (2) ; LEUNG S. (2) ; MILLER M. A. (2) ; JOHNSON K. (2) ; NORRIS B. (2) ; HASTIE T. (3) ; MCKINNEY S. (2) ; NIELSEN T. O. (2) ; HUNTSMAN D. G. (2) ; GILKS C. B. (2) ; WEST R. B. (3) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s) (1) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, ETATS-UNIS (2) Genetic Pathology Evaluation Centre of the Vancouver Coastal Research Institute, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, CANADA (3) Stanford University, Room L235, 300 Pasteur Drive, Stanford, CA 94305, ETATS-UNIS RÃ©sumÃ© / Abstract 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. Revue / Journal Title Breast cancer research and treatment ISSN 0167-6806 CODEN BCTRD6 Source / Source 2008, vol. 112, no3, pp. 453-459 [7 page(s) (article)] (33 ref.) Langue / Language Anglais Editeur / Publisher Springer, Dordrecht, PAYS-BAS (1981) (Revue) Mots-clÃ©s anglais / English Keywords Anatomic pathology ; Breast disease ; Mammary gland diseases ; Cancer ; Malignant tumor ; Human Epidermal growth factor Receptor 2 ; Survival ; Immunohistochemistry ; Gene overexpression ; Gene amplification ; Fluorescence in situ hybridization ; Breast cancer ; Follow up study ; Long term ; Cohort study ; Public health ; Analysis ; Copy number ; erbB2 Gene ; Protooncogene ; C-Onc gene ; Mots-clÃ©s franÃ§ais / French Keywords Anatomopathologie ; Pathologie du sein ; Pathologie de la glande mammaire ; Cancer ; Tumeur maligne ; RÃ©cepteur HER2 ; Survie ; Immunohistochimie ; Surexpression gÃ©nique ; Amplification gÃ©nique ; Hybridation in situ fluorescence ; Cancer du sein ; Etude longitudinale ; Long terme ; Etude cohorte ; SantÃ© publique ; Analyse ; Nombre copie ; GÃ¨ne erbB2 ; ProtooncogÃ¨ne ; GÃ¨ne onc cellulaire ; Mots-clÃ©s espagnols / Spanish Keywords AnatomÃa patolÃ³gica ; Seno patologÃa ; GlÃ¡ndula mamaria patologÃa ; CÃ¡ncer ; Tumor maligno ; Sobrevivencia ; InmunohistoquÃmica ; SobreexpresiÃ³n genÃ©tica ; AmplificaciÃ³n gÃ©nica ; HibridaciÃ³n in situ fluorescencia ; CÃ¡ncer del pecho ; Estudio longitudinal ; Largo plazo ; Estudio cohorte ; Salud pÃºblica ; AnÃ¡lisis ; NÃºmero copia ; Gen erbB2 ; Protooncogen ; Gen onc celular ; Mots-clÃ©s d'auteur / Author Keywords Breast cancer . Fluorescence in situ hybridization . HER2 amplification . Her2 overexpression ; Immunohistochemistry . Survival ; Localisation / Location INIST-CNRS, Cote INIST : 20699, 35400018402348.0070 NÂº notice refdoc (ud4) : 20901940