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Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer
Authors:Marie Klintman  Sidse Ørnbjerg Würtz  Ib Jarle Christensen  Pernille Bræmer Hertel  Mårten Fernö  Martin Malmberg  Henning Mouridsen  Frederik Cold  Anne-Sofie Schrohl  John A. Foekens  Per Malmström  Nils Brünner
Affiliation:1. Department of Oncology, Clinical Sciences, Barngatan 2B, Lund University, 221 85, Lund, Sweden
2. Faculty of Life Sciences, Department of Disease Biology, University of Copenhagen, Ridebanevej 9, 1870, Frederiksberg C, Denmark
3. Finsen Laboratory, Copenhagen Biocenter, Rigshospitalet, Ole Maal?es vej 5, 2200, Copenhagen, Denmark
4. Department of Oncology, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark
5. Department of Oncology R, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark
6. Department of Medical Oncology, Josephine Nefkens Institute, Erasmus MC Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands
Abstract: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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