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Elevated expression of polymorphonuclear leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease.

Foekens JA, Ries Ch, Look MP, Gippner-Steppert C, Klijn JG, Jochum M - Br. J. Cancer (2003)

Bottom Line: In the present study, we have measured with enzyme-linked immunosorbent assay the levels of total PMN-E in cytosolic extracts of 463 primary breast tumours, and have correlated their levels with the rate and duration of response on first-line tamoxifen therapy (387 patients) or chemotherapy (76 patients) in patients with locally advanced and/or distant metastatic breast cancer.Our results show that in logistic regression analysis for response to tamoxifen treatment in patients with advanced disease, high PMN-E tumour levels were associated with a poor rate of response compared with those with low PMN-E levels (odds ratio: OR, 0.40; 95% CI, 0.22-0.73; P=0.003).Our present results suggest that PMN-E is an independent predictive marker for the efficacy of tamoxifen treatment in patients with advanced breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed, Rotterdam, The Netherlands. j.foekens@erasmasmc.nl

ABSTRACT
Besides a variety of other proteases, polymorphonuclear leukocyte elastase (PMN-E) is also suggested to play a role in the processes of tumour cell invasion and metastasis. Yet, there is only limited data available on the relation between the tumour level of PMN-E and prognosis in patients with primary breast cancer, and no published information exists on its relation with the efficacy of response to systemic therapy in patients with advanced breast cancer. In the present study, we have measured with enzyme-linked immunosorbent assay the levels of total PMN-E in cytosolic extracts of 463 primary breast tumours, and have correlated their levels with the rate and duration of response on first-line tamoxifen therapy (387 patients) or chemotherapy (76 patients) in patients with locally advanced and/or distant metastatic breast cancer. Furthermore, the probabilities of progression-free survival and postrelapse survival were studied in relation to the tumour levels of PMN-E. Our results show that in logistic regression analysis for response to tamoxifen treatment in patients with advanced disease, high PMN-E tumour levels were associated with a poor rate of response compared with those with low PMN-E levels (odds ratio: OR, 0.40; 95% CI, 0.22-0.73; P=0.003). After correction for the contribution of the traditional predictive factors in multivariate analysis, the tumour PMN-E status was an independent predictor of response (P=0.01). Furthermore, a high tumour PMN-E level was related with a poor progression-free survival (P<0.001) and postrelapse survival (P=0.002) in a time-dependent analysis. In contrast, the tumour level of PMN-E was not significantly related with the efficacy of response to first-line chemotherapy in patients with advanced breast cancer. Our present results suggest that PMN-E is an independent predictive marker for the efficacy of tamoxifen treatment in patients with advanced breast cancer.

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Related in: MedlinePlus

Progression-free survival (A) and postrelapse survival (B) after start of first-line tamoxifen therapy in 387 patients with advanced breast cancer as a function of PMN-E status. Patients at risk are indicated. Cutoff point used, 20 ng PMN-E mg−1 protein.
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fig1: Progression-free survival (A) and postrelapse survival (B) after start of first-line tamoxifen therapy in 387 patients with advanced breast cancer as a function of PMN-E status. Patients at risk are indicated. Cutoff point used, 20 ng PMN-E mg−1 protein.

Mentions: The results of the Kaplan–Meier analysis for progression-free and postrelapse survival in all 387 patients, who received first-line tamoxifen treatment for advanced disease as a function of dichotomised PMN-E status, are shown in Figure 1A and BFigure 1


Elevated expression of polymorphonuclear leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease.

Foekens JA, Ries Ch, Look MP, Gippner-Steppert C, Klijn JG, Jochum M - Br. J. Cancer (2003)

Progression-free survival (A) and postrelapse survival (B) after start of first-line tamoxifen therapy in 387 patients with advanced breast cancer as a function of PMN-E status. Patients at risk are indicated. Cutoff point used, 20 ng PMN-E mg−1 protein.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376381&req=5

fig1: Progression-free survival (A) and postrelapse survival (B) after start of first-line tamoxifen therapy in 387 patients with advanced breast cancer as a function of PMN-E status. Patients at risk are indicated. Cutoff point used, 20 ng PMN-E mg−1 protein.
Mentions: The results of the Kaplan–Meier analysis for progression-free and postrelapse survival in all 387 patients, who received first-line tamoxifen treatment for advanced disease as a function of dichotomised PMN-E status, are shown in Figure 1A and BFigure 1

Bottom Line: In the present study, we have measured with enzyme-linked immunosorbent assay the levels of total PMN-E in cytosolic extracts of 463 primary breast tumours, and have correlated their levels with the rate and duration of response on first-line tamoxifen therapy (387 patients) or chemotherapy (76 patients) in patients with locally advanced and/or distant metastatic breast cancer.Our results show that in logistic regression analysis for response to tamoxifen treatment in patients with advanced disease, high PMN-E tumour levels were associated with a poor rate of response compared with those with low PMN-E levels (odds ratio: OR, 0.40; 95% CI, 0.22-0.73; P=0.003).Our present results suggest that PMN-E is an independent predictive marker for the efficacy of tamoxifen treatment in patients with advanced breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed, Rotterdam, The Netherlands. j.foekens@erasmasmc.nl

ABSTRACT
Besides a variety of other proteases, polymorphonuclear leukocyte elastase (PMN-E) is also suggested to play a role in the processes of tumour cell invasion and metastasis. Yet, there is only limited data available on the relation between the tumour level of PMN-E and prognosis in patients with primary breast cancer, and no published information exists on its relation with the efficacy of response to systemic therapy in patients with advanced breast cancer. In the present study, we have measured with enzyme-linked immunosorbent assay the levels of total PMN-E in cytosolic extracts of 463 primary breast tumours, and have correlated their levels with the rate and duration of response on first-line tamoxifen therapy (387 patients) or chemotherapy (76 patients) in patients with locally advanced and/or distant metastatic breast cancer. Furthermore, the probabilities of progression-free survival and postrelapse survival were studied in relation to the tumour levels of PMN-E. Our results show that in logistic regression analysis for response to tamoxifen treatment in patients with advanced disease, high PMN-E tumour levels were associated with a poor rate of response compared with those with low PMN-E levels (odds ratio: OR, 0.40; 95% CI, 0.22-0.73; P=0.003). After correction for the contribution of the traditional predictive factors in multivariate analysis, the tumour PMN-E status was an independent predictor of response (P=0.01). Furthermore, a high tumour PMN-E level was related with a poor progression-free survival (P<0.001) and postrelapse survival (P=0.002) in a time-dependent analysis. In contrast, the tumour level of PMN-E was not significantly related with the efficacy of response to first-line chemotherapy in patients with advanced breast cancer. Our present results suggest that PMN-E is an independent predictive marker for the efficacy of tamoxifen treatment in patients with advanced breast cancer.

Show MeSH
Related in: MedlinePlus