Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

Anne-Sofie Schrohl Rasmussen; Maxime P. Look; Marion E. Meijer-van Gelder; John A. Foekens; Nils Brünner

Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

Anne-Sofie Schrohl Rasmussen, Maxime P. Look, Marion E. Meijer-van Gelder, John A. Foekens, Nils Brünner

Abstract

Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006) suggesting that TIMP-1 may be a predictive marker in breast cancer patients.

Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen.

Patients and Methods: 525 pre-menopausal lymph node-positive patients were included; 324 patients received adjuvant CMF, 99 received an adjuvant anthracycline-containing regimen and 102 had no adjuvant chemotherapy. Total TIMP-1 levels were measured by use of ELISA in cytosolic extracts of frozen primary tumors. Using the untreated patient group as a reference group, we analyzed the benefit of adjuvant CMF and anthracyclines in TIMP-1 high and low patients, respectively. The median TIMP-1 concentration was used to dichotomize patients into high and low TIMP-1 groups. End points were disease-free and overall survival (DFS, OS).

Results: The median TIMP-1 level in the total patient group was 12,54 ng/mg of total protein (range, 0 - 112,9 ng/mg). TIMP-1 levels in subgroups according to adjuvant therapy were not significantly different (P=0,20). In a multivariate model including basic clinico-pathological parameters, TIMP-1 low and high patients benefited differentially from adjuvant CMF and anthracyclines when compared to untreated patients. In particular, patients with high tumor levels of TIMP-1 had little benefit from adjuvant anthracyclines. Hazard ratios (HR) and 95% confidence intervals (CI) are given in the table below for the analysis of DFS. A similar pattern was seen in the analyses of OS. In the group treated with CMF, both TIMP-1 low and high patients had significantly better survival than untreated patients (P<0,01). Among anthracycline-treated patients, those with TIMP-1 low tumors appear to benefit more from the adjuvant therapy than TIMP-1 high patients although these results did not reach significance in the present analyses.

CMF-treated (HR, 95% CI)

Anthracycline-treated (HR, 95% CI

TIMP-1 low

0,47 (0,31-0,72)

0,65 (0,39-1,07)

TIMP-1 high

0,58 (0,39-0,87)

0,90 (0,56-1,44)

Conclusion: This study suggests that high tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however, is small and should be enlarged to confirm our results. In the group treated with CMF, all patients benefit from the therapy with TIMP-1 high patients having slightly less benefit from the therapy than TIMP-1 low patients.

Original language	English
Publication date	2008
Publication status	Published - 2008
Event	San Antonio Breast Cancer Symposium 2008 - San Antonio, Texas, United States Duration: 10 Dec 2008 → 14 Dec 2008

Conference

Conference	San Antonio Breast Cancer Symposium 2008
Country/Territory	United States
City	San Antonio, Texas
Period	10/12/2008 → 14/12/2008

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

Rasmussen, A-S. S., Look, M. P., Meijer-van Gelder, M. E., Foekens, J. A., & Brünner, N. (2008). Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525). Poster session presented at San Antonio Breast Cancer Symposium 2008, San Antonio, Texas, United States.

Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525). / Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E. et al.

2008. Poster session presented at San Antonio Breast Cancer Symposium 2008, San Antonio, Texas, United States.

Research output: Contribution to conference › Poster › Research

Rasmussen, A-SS, Look, MP, Meijer-van Gelder, ME, Foekens, JA & Brünner, N 2008, ' Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)', San Antonio Breast Cancer Symposium 2008, San Antonio, Texas, United States, 10/12/2008 - 14/12/2008.

Rasmussen A-SS, Look MP, Meijer-van Gelder ME, Foekens JA, Brünner N. Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525). 2008. Poster session presented at San Antonio Breast Cancer Symposium 2008, San Antonio, Texas, United States.

Rasmussen, Anne-Sofie Schrohl ; Look, Maxime P. ; Meijer-van Gelder, Marion E. et al. / Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525). Poster session presented at San Antonio Breast Cancer Symposium 2008, San Antonio, Texas, United States.

@conference{f4378870c51811dd8ca2000ea68e967b,

title = " Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)",

abstract = " Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen.Patients and Methods: 525 pre-menopausal lymph node-positive patients were included; 324 patients received adjuvant CMF, 99 received an adjuvant anthracycline-containing regimen and 102 had no adjuvant chemotherapy. Total TIMP-1 levels were measured by use of ELISA in cytosolic extracts of frozen primary tumors. Using the untreated patient group as a reference group, we analyzed the benefit of adjuvant CMF and anthracyclines in TIMP-1 high and low patients, respectively. The median TIMP-1 concentration was used to dichotomize patients into high and low TIMP-1 groups. End points were disease-free and overall survival (DFS, OS).Results: The median TIMP-1 level in the total patient group was 12,54 ng/mg of total protein (range, 0 - 112,9 ng/mg). TIMP-1 levels in subgroups according to adjuvant therapy were not significantly different (P=0,20). In a multivariate model including basic clinico-pathological parameters, TIMP-1 low and high patients benefited differentially from adjuvant CMF and anthracyclines when compared to untreated patients. In particular, patients with high tumor levels of TIMP-1 had little benefit from adjuvant anthracyclines. Hazard ratios (HR) and 95% confidence intervals (CI) are given in the table below for the analysis of DFS. A similar pattern was seen in the analyses of OS. In the group treated with CMF, both TIMP-1 low and high patients had significantly better survival than untreated patients (P<0,01). Among anthracycline-treated patients, those with TIMP-1 low tumors appear to benefit more from the adjuvant therapy than TIMP-1 high patients although these results did not reach significance in the present analyses. CMF-treated (HR, 95% CI)Anthracycline-treated (HR, 95% CITIMP-1 low0,47 (0,31-0,72)0,65 (0,39-1,07)TIMP-1 high0,58 (0,39-0,87)0,90 (0,56-1,44) Conclusion: This study suggests that high tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however, is small and should be enlarged to confirm our results. In the group treated with CMF, all patients benefit from the therapy with TIMP-1 high patients having slightly less benefit from the therapy than TIMP-1 low patients.",

author = "Rasmussen, {Anne-Sofie Schrohl} and Look, {Maxime P.} and {Meijer-van Gelder}, {Marion E.} and Foekens, {John A.} and Nils Br{\"u}nner",

year = "2008",

language = "English",

note = "San Antonio Breast Cancer Symposium 2008 ; Conference date: 10-12-2008 Through 14-12-2008",

}

TY - CONF

T1 - Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

AU - Rasmussen, Anne-Sofie Schrohl

AU - Look, Maxime P.

AU - Meijer-van Gelder, Marion E.

AU - Foekens, John A.

AU - Brünner, Nils

PY - 2008

Y1 - 2008

N2 - Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen.Patients and Methods: 525 pre-menopausal lymph node-positive patients were included; 324 patients received adjuvant CMF, 99 received an adjuvant anthracycline-containing regimen and 102 had no adjuvant chemotherapy. Total TIMP-1 levels were measured by use of ELISA in cytosolic extracts of frozen primary tumors. Using the untreated patient group as a reference group, we analyzed the benefit of adjuvant CMF and anthracyclines in TIMP-1 high and low patients, respectively. The median TIMP-1 concentration was used to dichotomize patients into high and low TIMP-1 groups. End points were disease-free and overall survival (DFS, OS).Results: The median TIMP-1 level in the total patient group was 12,54 ng/mg of total protein (range, 0 - 112,9 ng/mg). TIMP-1 levels in subgroups according to adjuvant therapy were not significantly different (P=0,20). In a multivariate model including basic clinico-pathological parameters, TIMP-1 low and high patients benefited differentially from adjuvant CMF and anthracyclines when compared to untreated patients. In particular, patients with high tumor levels of TIMP-1 had little benefit from adjuvant anthracyclines. Hazard ratios (HR) and 95% confidence intervals (CI) are given in the table below for the analysis of DFS. A similar pattern was seen in the analyses of OS. In the group treated with CMF, both TIMP-1 low and high patients had significantly better survival than untreated patients (P<0,01). Among anthracycline-treated patients, those with TIMP-1 low tumors appear to benefit more from the adjuvant therapy than TIMP-1 high patients although these results did not reach significance in the present analyses. CMF-treated (HR, 95% CI)Anthracycline-treated (HR, 95% CITIMP-1 low0,47 (0,31-0,72)0,65 (0,39-1,07)TIMP-1 high0,58 (0,39-0,87)0,90 (0,56-1,44) Conclusion: This study suggests that high tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however, is small and should be enlarged to confirm our results. In the group treated with CMF, all patients benefit from the therapy with TIMP-1 high patients having slightly less benefit from the therapy than TIMP-1 low patients.

AB - Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen.Patients and Methods: 525 pre-menopausal lymph node-positive patients were included; 324 patients received adjuvant CMF, 99 received an adjuvant anthracycline-containing regimen and 102 had no adjuvant chemotherapy. Total TIMP-1 levels were measured by use of ELISA in cytosolic extracts of frozen primary tumors. Using the untreated patient group as a reference group, we analyzed the benefit of adjuvant CMF and anthracyclines in TIMP-1 high and low patients, respectively. The median TIMP-1 concentration was used to dichotomize patients into high and low TIMP-1 groups. End points were disease-free and overall survival (DFS, OS).Results: The median TIMP-1 level in the total patient group was 12,54 ng/mg of total protein (range, 0 - 112,9 ng/mg). TIMP-1 levels in subgroups according to adjuvant therapy were not significantly different (P=0,20). In a multivariate model including basic clinico-pathological parameters, TIMP-1 low and high patients benefited differentially from adjuvant CMF and anthracyclines when compared to untreated patients. In particular, patients with high tumor levels of TIMP-1 had little benefit from adjuvant anthracyclines. Hazard ratios (HR) and 95% confidence intervals (CI) are given in the table below for the analysis of DFS. A similar pattern was seen in the analyses of OS. In the group treated with CMF, both TIMP-1 low and high patients had significantly better survival than untreated patients (P<0,01). Among anthracycline-treated patients, those with TIMP-1 low tumors appear to benefit more from the adjuvant therapy than TIMP-1 high patients although these results did not reach significance in the present analyses. CMF-treated (HR, 95% CI)Anthracycline-treated (HR, 95% CITIMP-1 low0,47 (0,31-0,72)0,65 (0,39-1,07)TIMP-1 high0,58 (0,39-0,87)0,90 (0,56-1,44) Conclusion: This study suggests that high tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however, is small and should be enlarged to confirm our results. In the group treated with CMF, all patients benefit from the therapy with TIMP-1 high patients having slightly less benefit from the therapy than TIMP-1 low patients.

M3 - Poster

T2 - San Antonio Breast Cancer Symposium 2008

Y2 - 10 December 2008 through 14 December 2008

ER -

Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

Abstract

Conference

UN SDGs

Fingerprint

Cite this