Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer: A Danish Breast Cancer Cooperative Group Study

Gro L. Willemoe; Pernille Bræmer Hertel; Annette Bartels; Maj-Britt Jensen; Eva Balslev; Birgitte B. Rasmussen; H T Mouridsen; Bent Laursen Ejlertsen; Nils Brunner

doi:10.1016/j.ejca.2009.05.029

Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer: A Danish Breast Cancer Cooperative Group Study

Gro L. Willemoe, Pernille Bræmer Hertel, Annette Bartels, Maj-Britt Jensen, Eva Balslev, Birgitte B. Rasmussen, H T Mouridsen, Bent Laursen Ejlertsen, Nils Brunner

Department of Clinical Medicine

27 Citations (Scopus)

Abstract

PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell immunoreactivity. EXPERIMENTAL DESIGN: Tissue micro arrays from 647 patients randomly assigned to CMF or CEF in DBCG trial 89D were included. The primary end-point was invasive disease-free survival (IDFS). A central assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) status was performed using immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7. RESULTS: By central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative tumours had a significant longer IDFS than patients with TIMP-1 positive tumours (p=0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumours (hazard ratio (HR)=0.51; 95% confidence interval (CI): 0.31-0.84, p=0.0085), while no significant difference could be demonstrated among patients with TIMP-1 positive tumours (HR=0.88; 95% CI: 0.68-1.13, p=0.32). A non-significant TIMP-1 status (positive or negative) versus treatment (CMF or CEF) interaction was detected for IDFS (p=0.06) and OS (p=0.21). CONCLUSION: Lack of TIMP-1 tumour cell immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity

Original language	English
Journal	European Journal of Cancer
Volume	45
Issue number	14
Pages (from-to)	2528-2536
Number of pages	9
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2009.05.029
Publication status	Published - 2009

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Willemoe, G. L., Hertel, P. B., Bartels, A., Jensen, M-B., Balslev, E., Rasmussen, B. B., Mouridsen, H. T., Ejlertsen, B. L., & Brunner, N. (2009). Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer: A Danish Breast Cancer Cooperative Group Study. European Journal of Cancer, 45(14), 2528-2536. https://doi.org/10.1016/j.ejca.2009.05.029

Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer : A Danish Breast Cancer Cooperative Group Study. / Willemoe, Gro L.; Hertel, Pernille Bræmer; Bartels, Annette et al.

In: European Journal of Cancer, Vol. 45, No. 14, 2009, p. 2528-2536.

Research output: Contribution to journal › Journal article › Research › peer-review

Willemoe, GL, Hertel, PB, Bartels, A, Jensen, M-B, Balslev, E, Rasmussen, BB, Mouridsen, HT, Ejlertsen, BL & Brunner, N 2009, 'Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer: A Danish Breast Cancer Cooperative Group Study', European Journal of Cancer, vol. 45, no. 14, pp. 2528-2536. https://doi.org/10.1016/j.ejca.2009.05.029

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title = "Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer: A Danish Breast Cancer Cooperative Group Study",

abstract = "PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell immunoreactivity. EXPERIMENTAL DESIGN: Tissue micro arrays from 647 patients randomly assigned to CMF or CEF in DBCG trial 89D were included. The primary end-point was invasive disease-free survival (IDFS). A central assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) status was performed using immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7. RESULTS: By central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative tumours had a significant longer IDFS than patients with TIMP-1 positive tumours (p=0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumours (hazard ratio (HR)=0.51; 95% confidence interval (CI): 0.31-0.84, p=0.0085), while no significant difference could be demonstrated among patients with TIMP-1 positive tumours (HR=0.88; 95% CI: 0.68-1.13, p=0.32). A non-significant TIMP-1 status (positive or negative) versus treatment (CMF or CEF) interaction was detected for IDFS (p=0.06) and OS (p=0.21). CONCLUSION: Lack of TIMP-1 tumour cell immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity",

author = "Willemoe, {Gro L.} and Hertel, {Pernille Br{\ae}mer} and Annette Bartels and Maj-Britt Jensen and Eva Balslev and Rasmussen, {Birgitte B.} and Mouridsen, {H T} and Ejlertsen, {Bent Laursen} and Nils Brunner",

year = "2009",

doi = "10.1016/j.ejca.2009.05.029",

language = "English",

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pages = "2528--2536",

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T1 - Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer

T2 - A Danish Breast Cancer Cooperative Group Study

AU - Willemoe, Gro L.

AU - Hertel, Pernille Bræmer

AU - Bartels, Annette

AU - Jensen, Maj-Britt

AU - Balslev, Eva

AU - Rasmussen, Birgitte B.

AU - Mouridsen, H T

AU - Ejlertsen, Bent Laursen

AU - Brunner, Nils

PY - 2009

Y1 - 2009

N2 - PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell immunoreactivity. EXPERIMENTAL DESIGN: Tissue micro arrays from 647 patients randomly assigned to CMF or CEF in DBCG trial 89D were included. The primary end-point was invasive disease-free survival (IDFS). A central assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) status was performed using immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7. RESULTS: By central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative tumours had a significant longer IDFS than patients with TIMP-1 positive tumours (p=0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumours (hazard ratio (HR)=0.51; 95% confidence interval (CI): 0.31-0.84, p=0.0085), while no significant difference could be demonstrated among patients with TIMP-1 positive tumours (HR=0.88; 95% CI: 0.68-1.13, p=0.32). A non-significant TIMP-1 status (positive or negative) versus treatment (CMF or CEF) interaction was detected for IDFS (p=0.06) and OS (p=0.21). CONCLUSION: Lack of TIMP-1 tumour cell immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity

AB - PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell immunoreactivity. EXPERIMENTAL DESIGN: Tissue micro arrays from 647 patients randomly assigned to CMF or CEF in DBCG trial 89D were included. The primary end-point was invasive disease-free survival (IDFS). A central assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) status was performed using immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7. RESULTS: By central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative tumours had a significant longer IDFS than patients with TIMP-1 positive tumours (p=0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumours (hazard ratio (HR)=0.51; 95% confidence interval (CI): 0.31-0.84, p=0.0085), while no significant difference could be demonstrated among patients with TIMP-1 positive tumours (HR=0.88; 95% CI: 0.68-1.13, p=0.32). A non-significant TIMP-1 status (positive or negative) versus treatment (CMF or CEF) interaction was detected for IDFS (p=0.06) and OS (p=0.21). CONCLUSION: Lack of TIMP-1 tumour cell immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity

U2 - 10.1016/j.ejca.2009.05.029

DO - 10.1016/j.ejca.2009.05.029

M3 - Journal article

C2 - 19535243

SN - 0959-8049

VL - 45

SP - 2528

EP - 2536

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

IS - 14

ER -