Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab: Results from North Central Cancer Treatment Group adjuvant trial N9831

Alvaro Moreno Aspitia, David W. Hillman, Stephen H. Dyar, Kathleen S. Tenner, Julie Gralow, Peter A. Kaufman, Nancy E. Davidson, Jacqueline M. Lafky, Monica M. Reinholz, Wilma L. Lingle, Leila A. Kutteh, Walter P. Carney, Amylou Dueck, Edith A. Perez

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels <15 ng/mL (arm A: hazard ratio, 1.81; P =.0014; arm B: hazard ratio, 2.08; P =.0015; arm C: hazard ratio, 1.96; P =.01). Among the 124 patients who experienced disease recurrence, sHER2 levels increased from baseline to the time of recurrence in arms A and B but remained unchanged in arm C. Patients who had recurrence sHER2 levels ≥15 ng/mL had a shorter survival after recurrence with a 3-year overall survival rate of 51% compared with 77% for those who had recurrence sHER2 levels <15 ng/mL (hazard ratio, 2.36; 95% confidence interval, 1.19-4.70; P =.01). CONCLUSIONS In patients with early stage, HER2-positive breast cancer, a high baseline sHER2 level was identified as a prognostic marker associated with shorter disease-free survival, and a high sHER2 level at recurrence was predictive of shorter survival.

Original languageEnglish (US)
Pages (from-to)2675-2682
Number of pages8
JournalCancer
Volume119
Issue number15
DOIs
StatePublished - Aug 1 2013

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Breast Neoplasms
Drug Therapy
Recurrence
Neoplasms
Therapeutics
Nonparametric Statistics
human ERBB2 protein
Trastuzumab
Disease-Free Survival
Survival
Proportional Hazards Models
Linear Models
Survival Rate
Clinical Trials
Hormones
Confidence Intervals

Keywords

  • biomarker
  • breast cancer
  • extracellular domain
  • HER2-positive
  • human epidermal growth factor receptor 2
  • serum HER2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab : Results from North Central Cancer Treatment Group adjuvant trial N9831. / Moreno Aspitia, Alvaro; Hillman, David W.; Dyar, Stephen H.; Tenner, Kathleen S.; Gralow, Julie; Kaufman, Peter A.; Davidson, Nancy E.; Lafky, Jacqueline M.; Reinholz, Monica M.; Lingle, Wilma L.; Kutteh, Leila A.; Carney, Walter P.; Dueck, Amylou; Perez, Edith A.

In: Cancer, Vol. 119, No. 15, 01.08.2013, p. 2675-2682.

Research output: Contribution to journalArticle

Moreno Aspitia, Alvaro ; Hillman, David W. ; Dyar, Stephen H. ; Tenner, Kathleen S. ; Gralow, Julie ; Kaufman, Peter A. ; Davidson, Nancy E. ; Lafky, Jacqueline M. ; Reinholz, Monica M. ; Lingle, Wilma L. ; Kutteh, Leila A. ; Carney, Walter P. ; Dueck, Amylou ; Perez, Edith A. / Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab : Results from North Central Cancer Treatment Group adjuvant trial N9831. In: Cancer. 2013 ; Vol. 119, No. 15. pp. 2675-2682.
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title = "Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab: Results from North Central Cancer Treatment Group adjuvant trial N9831",
abstract = "BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels <15 ng/mL (arm A: hazard ratio, 1.81; P =.0014; arm B: hazard ratio, 2.08; P =.0015; arm C: hazard ratio, 1.96; P =.01). Among the 124 patients who experienced disease recurrence, sHER2 levels increased from baseline to the time of recurrence in arms A and B but remained unchanged in arm C. Patients who had recurrence sHER2 levels ≥15 ng/mL had a shorter survival after recurrence with a 3-year overall survival rate of 51{\%} compared with 77{\%} for those who had recurrence sHER2 levels <15 ng/mL (hazard ratio, 2.36; 95{\%} confidence interval, 1.19-4.70; P =.01). CONCLUSIONS In patients with early stage, HER2-positive breast cancer, a high baseline sHER2 level was identified as a prognostic marker associated with shorter disease-free survival, and a high sHER2 level at recurrence was predictive of shorter survival.",
keywords = "biomarker, breast cancer, extracellular domain, HER2-positive, human epidermal growth factor receptor 2, serum HER2",
author = "{Moreno Aspitia}, Alvaro and Hillman, {David W.} and Dyar, {Stephen H.} and Tenner, {Kathleen S.} and Julie Gralow and Kaufman, {Peter A.} and Davidson, {Nancy E.} and Lafky, {Jacqueline M.} and Reinholz, {Monica M.} and Lingle, {Wilma L.} and Kutteh, {Leila A.} and Carney, {Walter P.} and Amylou Dueck and Perez, {Edith A.}",
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TY - JOUR

T1 - Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab

T2 - Results from North Central Cancer Treatment Group adjuvant trial N9831

AU - Moreno Aspitia, Alvaro

AU - Hillman, David W.

AU - Dyar, Stephen H.

AU - Tenner, Kathleen S.

AU - Gralow, Julie

AU - Kaufman, Peter A.

AU - Davidson, Nancy E.

AU - Lafky, Jacqueline M.

AU - Reinholz, Monica M.

AU - Lingle, Wilma L.

AU - Kutteh, Leila A.

AU - Carney, Walter P.

AU - Dueck, Amylou

AU - Perez, Edith A.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels <15 ng/mL (arm A: hazard ratio, 1.81; P =.0014; arm B: hazard ratio, 2.08; P =.0015; arm C: hazard ratio, 1.96; P =.01). Among the 124 patients who experienced disease recurrence, sHER2 levels increased from baseline to the time of recurrence in arms A and B but remained unchanged in arm C. Patients who had recurrence sHER2 levels ≥15 ng/mL had a shorter survival after recurrence with a 3-year overall survival rate of 51% compared with 77% for those who had recurrence sHER2 levels <15 ng/mL (hazard ratio, 2.36; 95% confidence interval, 1.19-4.70; P =.01). CONCLUSIONS In patients with early stage, HER2-positive breast cancer, a high baseline sHER2 level was identified as a prognostic marker associated with shorter disease-free survival, and a high sHER2 level at recurrence was predictive of shorter survival.

AB - BACKGROUND Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2-positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial. METHODS The objectives were to describe sHER2 levels during treatment and at the time of recurrence in patients who were randomized to treatment arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab), and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available from 2318 patients, serial samples were available from 105 patients, and recurrence samples were available from 124 patients. The cutoff sHER2 value for the assay was 15 ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank-sum tests, and Cox regression models. RESULTS There were differences between groups in terms of age, menopausal status, and hormone receptor status. Within treatment arms A, B, and C, patients who had baseline sHER2 levels ≥15 ng/mL had worse disease-free survival than patients who had baseline sHER2 levels <15 ng/mL (arm A: hazard ratio, 1.81; P =.0014; arm B: hazard ratio, 2.08; P =.0015; arm C: hazard ratio, 1.96; P =.01). Among the 124 patients who experienced disease recurrence, sHER2 levels increased from baseline to the time of recurrence in arms A and B but remained unchanged in arm C. Patients who had recurrence sHER2 levels ≥15 ng/mL had a shorter survival after recurrence with a 3-year overall survival rate of 51% compared with 77% for those who had recurrence sHER2 levels <15 ng/mL (hazard ratio, 2.36; 95% confidence interval, 1.19-4.70; P =.01). CONCLUSIONS In patients with early stage, HER2-positive breast cancer, a high baseline sHER2 level was identified as a prognostic marker associated with shorter disease-free survival, and a high sHER2 level at recurrence was predictive of shorter survival.

KW - biomarker

KW - breast cancer

KW - extracellular domain

KW - HER2-positive

KW - human epidermal growth factor receptor 2

KW - serum HER2

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