TIMP-1 and responsiveness to gemcitabine in advanced breast cancer; results from a randomized phase III trial from the Danish breast cancer cooperative group
| Autor: | Charlotte Jørgensen, Annette Bartels, Nils Brünner, Christina Annette Bjerre, Dorte Lisbet Nielsen, Karsten Bjerre, Eva Balslev, Bent Ejlertsen |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Oncology Antimetabolites Antineoplastic Cancer Research medicine.medical_specialty Denmark Breast Neoplasms Docetaxel Deoxycytidine Disease-Free Survival TIMP-1 Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Genetics medicine Humans Neoplasm Metastasis Aged Tissue Inhibitor of Metalloproteinase-1 Predictive marker business.industry Hazard ratio Cancer Middle Aged Prognosis medicine.disease Gemcitabine Metastatic breast cancer Primary tumor Gene Expression Regulation Neoplastic Treatment Outcome Female Taxoids Prediction business Research Article medicine.drug |
| Zdroj: | BMC Cancer Jørgensen, C L T, Bjerre, C A, Ejlertsen, B L, Bjerre, K D, Balslev, E, Bartels, A, Brünner, N & Nielsen, D L 2014, ' TIMP-1 and responsiveness to gemcitabine in advanced breast cancer : results from a randomized phase III trial from the Danish breast cancer cooperative group ', B M C Cancer, vol. 14, 360 . https://doi.org/10.1186/1471-2407-14-360 |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-14-360 |
| Popis: | Background: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has anti-apoptotic functions, which may protect TIMP-1 positive cancer cells from the effects of chemotherapy such as docetaxel and gemcitabine. The purpose of the present study was to evaluate TIMP-1 immunoreactivity as a prognostic and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). Methods: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1 status was performed retrospectively on primary tumor whole-tissue sections by immunohistochemistry and tumor samples were considered positive if epithelial breast cancer cells were stained by the anti-TIMP-1 monoclonal antibody VT7. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between TIMP-1 status and outcome after chemotherapy were analyzed by Kaplan-Meier estimates and Cox proportional hazards regression models. Results: TIMP-1 status was available from 264 of 337 patients and 210 (80%) of the tumors were classified as cancer cell TIMP-1 positive. No significant difference for TTP between TIMP-1 positive versus TIMP-1 negative patients was observed in multivariate analysis, and RR did not differ according to TIMP-1 status. However, patients with TIMP-1 positive tumors had a significant reduction in OS events (hazard ratio = 0.71, 95% confidence interval (CI) = 0.52-0.98, P = 0.03). Additionally, a borderline significant interaction for OS was observed between TIMP-1 status and benefit from GD compared to D (Pinteraction= 0.06) such that median OS increased by nine months for TIMP-1 negative patients receiving GD. Conclusions: TIMP-1 status was an independent prognostic factor for OS but not TTP in patients with advanced breast cancer receiving either D or GD. There was no statistically significant interaction between TIMP-1 status and treatment, but a trend towards an incremental OS from the addition of gemcitabine to docetaxel in patients with TIMP-1 negative tumors suggests further investigation. |
| Databáze: | OpenAIRE |
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