Elevated plasma tissue inhibitor of metalloproteinase-1 level predicts decreased response and survival in metastatic breast cancer

Allan Lipton, Suhail M. Ali, Kim Leitzel, Laurence Demers, Dean B. Evans, Peter Hamer, Sheryl Brown-Shimer, Karen Pierce, Walter Carney

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Tissue inhibitors of metalloproteinase (TIMPs) have at least 2 different functions. They inhibit the catalytic activity of matrix metalloproteinases, and they act as growth factors. METHODS. Pretreatment ethylenediamine tetracetic acid plasma TIMP-1 was assayed from 251 patients who were enrolled in a Phase III, second-line, hormone therapy trial, and from a control group of 50 healthy, postmenopausal women by using the TIMP-1 enzyme-linked immunosorbent assay. RESULTS. The plasma TIMP-1 levels from the postmenopausal control group (n = 50 women) were 201 ± 86 ng/mL mean ± standard deviation (range, 49-455 ng/mL). The upper limit of normal was defined as the mean ± 2 standard deviations of the control group (373 ng/mL). Patient pretreatment plasma TIMP-1 levels ranged from 70 ng/mL to 982 ng/mL. Plasma TIMP-1 was elevated above the mean + 2 standard deviations of the control group (373 ng/mL) in 19 patients (7.6%). In univariate analysis, patients who had elevated versus normal plasma TIMP-1 levels had a reduced clinical benefit rate (CBR) (16% vs 42%; P = .03). The time to progression (TTP) (84 days vs 174 days; P < .0001) and overall survival (141 days vs 860 days; P = .0001) also were significantly shorter in patients who had elevated TIMP-1 levels. TTP and overall survival also were significantly shorter in patients who had higher TIMP-1 plasma levels when it was analyzed as a continuous variable. In multivariate analysis, elevated plasma TIMP-1 level remained a prognostic factor for reduced overall survival (P < .0001) along with elevated serum HER-2/neu (P <.0001) and the presence of visceral metastases (P = .008). CONCLUSIONS. Elevated pretreatment plasma levels of TIMP-1 predicted a decreased response to second-line hormone therapy and reduced survival in women with metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)1933-1939
Number of pages7
JournalCancer
Volume109
Issue number10
DOIs
StatePublished - May 15 2007

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Tissue Inhibitor of Metalloproteinase-1
Breast Neoplasms
Survival
Control Groups
ethylenediamine
Hormones
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinases
Intercellular Signaling Peptides and Proteins
Multivariate Analysis
Enzyme-Linked Immunosorbent Assay
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lipton, Allan ; Ali, Suhail M. ; Leitzel, Kim ; Demers, Laurence ; Evans, Dean B. ; Hamer, Peter ; Brown-Shimer, Sheryl ; Pierce, Karen ; Carney, Walter. / Elevated plasma tissue inhibitor of metalloproteinase-1 level predicts decreased response and survival in metastatic breast cancer. In: Cancer. 2007 ; Vol. 109, No. 10. pp. 1933-1939.
@article{77180ccb7f69405f97b4369da0cbc27a,
title = "Elevated plasma tissue inhibitor of metalloproteinase-1 level predicts decreased response and survival in metastatic breast cancer",
abstract = "BACKGROUND. Tissue inhibitors of metalloproteinase (TIMPs) have at least 2 different functions. They inhibit the catalytic activity of matrix metalloproteinases, and they act as growth factors. METHODS. Pretreatment ethylenediamine tetracetic acid plasma TIMP-1 was assayed from 251 patients who were enrolled in a Phase III, second-line, hormone therapy trial, and from a control group of 50 healthy, postmenopausal women by using the TIMP-1 enzyme-linked immunosorbent assay. RESULTS. The plasma TIMP-1 levels from the postmenopausal control group (n = 50 women) were 201 ± 86 ng/mL mean ± standard deviation (range, 49-455 ng/mL). The upper limit of normal was defined as the mean ± 2 standard deviations of the control group (373 ng/mL). Patient pretreatment plasma TIMP-1 levels ranged from 70 ng/mL to 982 ng/mL. Plasma TIMP-1 was elevated above the mean + 2 standard deviations of the control group (373 ng/mL) in 19 patients (7.6{\%}). In univariate analysis, patients who had elevated versus normal plasma TIMP-1 levels had a reduced clinical benefit rate (CBR) (16{\%} vs 42{\%}; P = .03). The time to progression (TTP) (84 days vs 174 days; P < .0001) and overall survival (141 days vs 860 days; P = .0001) also were significantly shorter in patients who had elevated TIMP-1 levels. TTP and overall survival also were significantly shorter in patients who had higher TIMP-1 plasma levels when it was analyzed as a continuous variable. In multivariate analysis, elevated plasma TIMP-1 level remained a prognostic factor for reduced overall survival (P < .0001) along with elevated serum HER-2/neu (P <.0001) and the presence of visceral metastases (P = .008). CONCLUSIONS. Elevated pretreatment plasma levels of TIMP-1 predicted a decreased response to second-line hormone therapy and reduced survival in women with metastatic breast cancer.",
author = "Allan Lipton and Ali, {Suhail M.} and Kim Leitzel and Laurence Demers and Evans, {Dean B.} and Peter Hamer and Sheryl Brown-Shimer and Karen Pierce and Walter Carney",
year = "2007",
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doi = "10.1002/cncr.22637",
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Lipton, A, Ali, SM, Leitzel, K, Demers, L, Evans, DB, Hamer, P, Brown-Shimer, S, Pierce, K & Carney, W 2007, 'Elevated plasma tissue inhibitor of metalloproteinase-1 level predicts decreased response and survival in metastatic breast cancer', Cancer, vol. 109, no. 10, pp. 1933-1939. https://doi.org/10.1002/cncr.22637

Elevated plasma tissue inhibitor of metalloproteinase-1 level predicts decreased response and survival in metastatic breast cancer. / Lipton, Allan; Ali, Suhail M.; Leitzel, Kim; Demers, Laurence; Evans, Dean B.; Hamer, Peter; Brown-Shimer, Sheryl; Pierce, Karen; Carney, Walter.

In: Cancer, Vol. 109, No. 10, 15.05.2007, p. 1933-1939.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Elevated plasma tissue inhibitor of metalloproteinase-1 level predicts decreased response and survival in metastatic breast cancer

AU - Lipton, Allan

AU - Ali, Suhail M.

AU - Leitzel, Kim

AU - Demers, Laurence

AU - Evans, Dean B.

AU - Hamer, Peter

AU - Brown-Shimer, Sheryl

AU - Pierce, Karen

AU - Carney, Walter

PY - 2007/5/15

Y1 - 2007/5/15

N2 - BACKGROUND. Tissue inhibitors of metalloproteinase (TIMPs) have at least 2 different functions. They inhibit the catalytic activity of matrix metalloproteinases, and they act as growth factors. METHODS. Pretreatment ethylenediamine tetracetic acid plasma TIMP-1 was assayed from 251 patients who were enrolled in a Phase III, second-line, hormone therapy trial, and from a control group of 50 healthy, postmenopausal women by using the TIMP-1 enzyme-linked immunosorbent assay. RESULTS. The plasma TIMP-1 levels from the postmenopausal control group (n = 50 women) were 201 ± 86 ng/mL mean ± standard deviation (range, 49-455 ng/mL). The upper limit of normal was defined as the mean ± 2 standard deviations of the control group (373 ng/mL). Patient pretreatment plasma TIMP-1 levels ranged from 70 ng/mL to 982 ng/mL. Plasma TIMP-1 was elevated above the mean + 2 standard deviations of the control group (373 ng/mL) in 19 patients (7.6%). In univariate analysis, patients who had elevated versus normal plasma TIMP-1 levels had a reduced clinical benefit rate (CBR) (16% vs 42%; P = .03). The time to progression (TTP) (84 days vs 174 days; P < .0001) and overall survival (141 days vs 860 days; P = .0001) also were significantly shorter in patients who had elevated TIMP-1 levels. TTP and overall survival also were significantly shorter in patients who had higher TIMP-1 plasma levels when it was analyzed as a continuous variable. In multivariate analysis, elevated plasma TIMP-1 level remained a prognostic factor for reduced overall survival (P < .0001) along with elevated serum HER-2/neu (P <.0001) and the presence of visceral metastases (P = .008). CONCLUSIONS. Elevated pretreatment plasma levels of TIMP-1 predicted a decreased response to second-line hormone therapy and reduced survival in women with metastatic breast cancer.

AB - BACKGROUND. Tissue inhibitors of metalloproteinase (TIMPs) have at least 2 different functions. They inhibit the catalytic activity of matrix metalloproteinases, and they act as growth factors. METHODS. Pretreatment ethylenediamine tetracetic acid plasma TIMP-1 was assayed from 251 patients who were enrolled in a Phase III, second-line, hormone therapy trial, and from a control group of 50 healthy, postmenopausal women by using the TIMP-1 enzyme-linked immunosorbent assay. RESULTS. The plasma TIMP-1 levels from the postmenopausal control group (n = 50 women) were 201 ± 86 ng/mL mean ± standard deviation (range, 49-455 ng/mL). The upper limit of normal was defined as the mean ± 2 standard deviations of the control group (373 ng/mL). Patient pretreatment plasma TIMP-1 levels ranged from 70 ng/mL to 982 ng/mL. Plasma TIMP-1 was elevated above the mean + 2 standard deviations of the control group (373 ng/mL) in 19 patients (7.6%). In univariate analysis, patients who had elevated versus normal plasma TIMP-1 levels had a reduced clinical benefit rate (CBR) (16% vs 42%; P = .03). The time to progression (TTP) (84 days vs 174 days; P < .0001) and overall survival (141 days vs 860 days; P = .0001) also were significantly shorter in patients who had elevated TIMP-1 levels. TTP and overall survival also were significantly shorter in patients who had higher TIMP-1 plasma levels when it was analyzed as a continuous variable. In multivariate analysis, elevated plasma TIMP-1 level remained a prognostic factor for reduced overall survival (P < .0001) along with elevated serum HER-2/neu (P <.0001) and the presence of visceral metastases (P = .008). CONCLUSIONS. Elevated pretreatment plasma levels of TIMP-1 predicted a decreased response to second-line hormone therapy and reduced survival in women with metastatic breast cancer.

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