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

Mitch Dowsett, Marion Procter, Worta McCaskill-Stevens, Evandro De Azambuja, Urania Dafni, Josef Rueschoff, Bruce Jordan, Stella Dolci, Mark Abramovitz, Oliver Stoss, Giuseppe Viale, Richard D. Gelber, Martine Piccart-Gebhart, Brian Leyland-Jones

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Abstract

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.

Original languageEnglish
Pages (from-to)2962-2969
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number18
DOIs
Publication statusPublished - Jun 20 2009

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Adjuvant Chemotherapy
Disease-Free Survival
Fluorescence In Situ Hybridization
human ERBB2 protein
Trastuzumab
erbB-1 Genes
Gene Dosage
Breast Neoplasms
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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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. / Dowsett, Mitch; Procter, Marion; McCaskill-Stevens, Worta; De Azambuja, Evandro; Dafni, Urania; Rueschoff, Josef; Jordan, Bruce; Dolci, Stella; Abramovitz, Mark; Stoss, Oliver; Viale, Giuseppe; Gelber, Richard D.; Piccart-Gebhart, Martine; Leyland-Jones, Brian.

In: Journal of Clinical Oncology, Vol. 27, No. 18, 20.06.2009, p. 2962-2969.

Research output: Contribution to journalArticle

Dowsett, M, Procter, M, McCaskill-Stevens, W, De Azambuja, E, Dafni, U, Rueschoff, J, Jordan, B, Dolci, S, Abramovitz, M, Stoss, O, Viale, G, Gelber, RD, Piccart-Gebhart, M & Leyland-Jones, B 2009, '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', Journal of Clinical Oncology, vol. 27, no. 18, pp. 2962-2969. https://doi.org/10.1200/JCO.2008.19.7939
Dowsett, Mitch ; Procter, Marion ; McCaskill-Stevens, Worta ; De Azambuja, Evandro ; Dafni, Urania ; Rueschoff, Josef ; Jordan, Bruce ; Dolci, Stella ; Abramovitz, Mark ; Stoss, Oliver ; Viale, Giuseppe ; Gelber, Richard D. ; Piccart-Gebhart, Martine ; Leyland-Jones, Brian. / 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. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 18. pp. 2962-2969.
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abstract = "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.",
author = "Mitch Dowsett and Marion Procter and Worta McCaskill-Stevens and {De Azambuja}, Evandro and Urania Dafni and Josef Rueschoff and Bruce Jordan and Stella Dolci and Mark Abramovitz and Oliver Stoss and Giuseppe Viale and Gelber, {Richard D.} and Martine Piccart-Gebhart and Brian Leyland-Jones",
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T1 - Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab

T2 - The HERA trial

AU - Dowsett, Mitch

AU - Procter, Marion

AU - McCaskill-Stevens, Worta

AU - De Azambuja, Evandro

AU - Dafni, Urania

AU - Rueschoff, Josef

AU - Jordan, Bruce

AU - Dolci, Stella

AU - Abramovitz, Mark

AU - Stoss, Oliver

AU - Viale, Giuseppe

AU - Gelber, Richard D.

AU - Piccart-Gebhart, Martine

AU - Leyland-Jones, Brian

PY - 2009/6/20

Y1 - 2009/6/20

N2 - 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.

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