Prognostic Significance of Tissue Inhibitor of Metalloproteinase-1 in Breast Cancer

Abstract

Introduction. Despite advances in breast cancer systemic treatment, new prognostic and predictive factors are still needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic significance of TIMP-1 in breast cancer. Methods. A single center-based case-control study was applied. Primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1. Results. At the optimized cut-point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.64 (P = 0.04), but without significant differences in overall survival (HR 1.29, P = 0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0, P = 0.92), there was a tendency for short overall survival in patients with high expression (HR 1.41, P = 0.21). Conclusions. Our data indicate that elevated TIMP-1 RNA levels are independently prognostic for early recurrence, and there is a tendency for association of high cytoplasmic TIMP-1 protein levels with short survival in primary breast cancer.

Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

“…Interestingly, the samples with metastasis in this study showed a tendency to an increased expression of TIMP-1 in comparison with samples from patients without metastasis. Those results must be considered a tendency, since they had not statistically significant support; anyway this fact is mentioned, because other authors [22, 23] previously reported elevated TIMP-1 in association with metastasis, suggesting that the tendency observed in our studies is perhaps real (and statistics could be easily corrected increasing the number of samples). In the interim, we have not enough evidence to support this molecule as a participant in the occurrence of metastasis in ductal breast cancer.…”

The Predictive and Prognostic Role of Topoisomerase IIα and Tissue Inhibitor of Metalloproteinases 1 Expression in Locally Advanced Breast Carcinoma of Egyptian Patients Treated With Anthracycline-based Neoadjuvant Chemotherapy

“…17,48 In our study; although TIMP-1 overexpression was associated with poor response to NAT, this did not lead to a significant prognostic value.…”

“…5,36,58,59 Finally, other studies reported no correlation between TOP2a gene amplification or overexpression and survival rate. 48,60,61 Patients who attain a complete response may experience long-term survival or be cured of the disease; and the pCR rate is one of the good prognostic factors independent of the initial tumor stage and other prognostic markers. 62 We proved that TOP2a overexpression is associated with favorable response to anthracycline-based chemotherapy.…”

Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy

“…Moreover, molecular phenotypes have become increasingly valuable in guiding treatment decisions. However, these markers remain imperfect tools and, therefore, new prognostic and predictive factors are still required to optimize treatments among BC patients [5].…”