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

Marie Klintman (1) , Sidse Ørnbjerg Würtz (2) , Ib Jarle Christensen (3) , Pernille Bræmer Hertel (2) , Mårten Fernö (1) , Martin Malmberg (1) , Henning Mouridsen (4) , Frederik Cold (5) , Anne-Sofie Schrohl (2) , John A. Foekens (6) , Per Malmström (1) , Nils Brünner (2)

1 Department of Oncology, Clinical Sciences, Barngatan 2B
2 Faculty of Life Sciences, Department of Disease Biology
3 Finsen Laboratory, Copenhagen Biocenter
4 Department of Oncology
5 Department of Oncology R
6 Department of Medical Oncology, Josephine Nefkens Institute

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,  = 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.

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

Marie Klintman, Sidse Ørnbjerg Würtz, Ib Jarle Christensen, Pernille Bræmer Hertel, Mårten Fernö, et al.. Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer. Breast Cancer Research and Treatment, 2009, 121 (2), pp.365-371. ⟨10.1007/s10549-009-0483-1⟩. ⟨hal-00535387⟩