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

• Published in: Breast cancer research and treatment Vol. 121; no. 2; pp. 365 - 371
• Main Authors: Klintman, Marie, Ørnbjerg Würtz, Sidse, Christensen, Ib Jarle, Bræmer Hertel, Pernille, Fernö, Mårten, Malmberg, Martin, Mouridsen, Henning, Cold, Frederik, Schrohl, Anne-Sofie, Foekens, John A, Malmström, Per, Brünner, Nils
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.06.2010; Springer US; Springer; Springer Nature B.V; Springer Verlag
• Subjects: Adult; analysis; Antineoplastic Agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers; Biomarkers, Tumor; Biomarkers, Tumor - analysis; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Cancer; Cancer and Oncology; Cancer och onkologi; Cancer research; Cancer therapies; Chemotherapy; Clinical Medicine; Development and progression; Disease-Free Survival; drug therapy; Enzyme-Linked Immunosorbent Assay; Female; genetics; Gynecology. Andrology. Obstetrics; Humans; Klinisk medicin; Mammary gland diseases; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; metabolism; Metastasis; Middle Aged; mortality; Oncology; Preclinical Study; Predictive marker; Prognosis; Resistance; therapeutic use; TIMP-1; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-1 - analysis; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Treatment Outcome; Tumor extracts; Tumors; Denmark; Sweden; Resistance; Chemotherapy; Breast cancer; TIMP-1; Tumor extracts; Predictive marker; Breast disease; Tumoral tissue; Tissue inhibitor metalloproteinase 1; Biological marker; Extract; Metastasis; Malignant tumor; Induction treatment; First line treatment; Mammary gland diseases; Treatment; Advanced stage; Cancer
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-009-0483-1

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.