4.5 Article

Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer

Journal

BREAST CANCER RESEARCH AND TREATMENT
Volume 121, Issue 2, Pages 365-371

Publisher

SPRINGER
DOI: 10.1007/s10549-009-0483-1

Keywords

TIMP-1; Predictive marker; Breast cancer; Resistance; Chemotherapy; Tumor extracts

Categories

Funding

  1. Swedish Cancer Society
  2. Swedish Research Council
  3. Gunnar, Arvid, and Elisabeth Nilsson Foundation
  4. Mrs Berta Kamprad Foundation
  5. University Hospital of Lund Research Foundation
  6. Governmental Funding of Clinical Research within the National Health Service
  7. Danish Cancer Society, Danish Center for Translational Breast Cancer Research
  8. A Race Against Breast Cancer
  9. Ministry for Health and Prevention
  10. Danish Strategic Research Council for Food and Health
  11. Sino-Danish Breast Cancer Research Centre

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In a previous study from our laboratory, high tumor levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) have been associated with an adverse response to chemotherapy in metastatic breast cancer suggesting that TIMP-1, which is known to inhibit apoptosis, may be a new predictive marker in this disease. The purpose of this study was to investigate the association between TIMP-1 and objective response to chemotherapy in an independent patient population consisting of patients with metastatic breast cancer from Sweden and Denmark. TIMP-1 was measured using ELISA in 162 primary tumor extracts from patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0.97-2.62, P = 0.07). This OR is very similar to the result from our previous study. Increasing levels of TIMP-1 were also associated with a shorter disease-free survival and overall survival, however, not statistically significant. The results from the present study support previous data that TIMP-1 is associated with objective response to chemotherapy for metastatic breast cancer.

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