HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial

Edith A. Perez, Monica M. Reinholz, David W. Hillman, Kathleen S. Tenner, Matthew J. Schroeder, Nancy E. Davidson, Silvana Martino, George W. Sledge, Lyndsay N. Harris, Julie R. Gralow, Amylou C. Dueck, Rhett P. Ketterling, James N. Ingle, Wilma L. Lingle, Peter A. Kaufman, Daniel W. Visscher, Robert B. Jenkins

Research output: Contribution to journalArticle

Abstract

Purpose: We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. Patients and Methods: All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). Results: Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P <.0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P <.006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor-positive or -negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. Conclusion: These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.

Original languageEnglish (US)
Pages (from-to)4307-4315
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number28
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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Chromosomes, Human, Pair 17
Fluorescence In Situ Hybridization
Neoplasms
Centromere
Immunohistochemistry
Hormones
Disease-Free Survival
Trastuzumab
human ERBB2 protein
erbB-1 Genes
Drug Therapy
Paclitaxel
Doxorubicin
Cyclophosphamide
Patient Selection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Perez, E. A., Reinholz, M. M., Hillman, D. W., Tenner, K. S., Schroeder, M. J., Davidson, N. E., ... Jenkins, R. B. (2010). HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. Journal of Clinical Oncology, 28(28), 4307-4315. https://doi.org/10.1200/JCO.2009.26.2154

HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. / Perez, Edith A.; Reinholz, Monica M.; Hillman, David W.; Tenner, Kathleen S.; Schroeder, Matthew J.; Davidson, Nancy E.; Martino, Silvana; Sledge, George W.; Harris, Lyndsay N.; Gralow, Julie R.; Dueck, Amylou C.; Ketterling, Rhett P.; Ingle, James N.; Lingle, Wilma L.; Kaufman, Peter A.; Visscher, Daniel W.; Jenkins, Robert B.

In: Journal of Clinical Oncology, Vol. 28, No. 28, 01.10.2010, p. 4307-4315.

Research output: Contribution to journalArticle

Perez, EA, Reinholz, MM, Hillman, DW, Tenner, KS, Schroeder, MJ, Davidson, NE, Martino, S, Sledge, GW, Harris, LN, Gralow, JR, Dueck, AC, Ketterling, RP, Ingle, JN, Lingle, WL, Kaufman, PA, Visscher, DW & Jenkins, RB 2010, 'HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial', Journal of Clinical Oncology, vol. 28, no. 28, pp. 4307-4315. https://doi.org/10.1200/JCO.2009.26.2154
Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE et al. HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. Journal of Clinical Oncology. 2010 Oct 1;28(28):4307-4315. https://doi.org/10.1200/JCO.2009.26.2154
Perez, Edith A. ; Reinholz, Monica M. ; Hillman, David W. ; Tenner, Kathleen S. ; Schroeder, Matthew J. ; Davidson, Nancy E. ; Martino, Silvana ; Sledge, George W. ; Harris, Lyndsay N. ; Gralow, Julie R. ; Dueck, Amylou C. ; Ketterling, Rhett P. ; Ingle, James N. ; Lingle, Wilma L. ; Kaufman, Peter A. ; Visscher, Daniel W. ; Jenkins, Robert B. / HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 28. pp. 4307-4315.
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abstract = "Purpose: We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. Patients and Methods: All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). Results: Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P <.0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P <.006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78{\%} v 68{\%}; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor-positive or -negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. Conclusion: These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.",
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T1 - HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial

AU - Perez, Edith A.

AU - Reinholz, Monica M.

AU - Hillman, David W.

AU - Tenner, Kathleen S.

AU - Schroeder, Matthew J.

AU - Davidson, Nancy E.

AU - Martino, Silvana

AU - Sledge, George W.

AU - Harris, Lyndsay N.

AU - Gralow, Julie R.

AU - Dueck, Amylou C.

AU - Ketterling, Rhett P.

AU - Ingle, James N.

AU - Lingle, Wilma L.

AU - Kaufman, Peter A.

AU - Visscher, Daniel W.

AU - Jenkins, Robert B.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Purpose: We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. Patients and Methods: All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). Results: Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P <.0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P <.006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor-positive or -negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. Conclusion: These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.

AB - Purpose: We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. Patients and Methods: All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). Results: Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P <.0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P <.006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor-positive or -negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. Conclusion: These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.

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