IntroductionEstrogen receptor (ER) determination is a standard tool used to evaluate the prognosis of breast cancer (BC) and progesterone receptor (PgR) expression, which is determined at the same time, can reflect ER functionality.1 However, simply ascertaining the ER and PgR status might be insufficient to accurately appraise the prognosis of patients or their ability to respond to treatment.
2Some other indicators recently recognized as prognostic factors 3 will probably be included in the near future as routine parameters for personalized therapeutics. In particular, those proteins that reflect the functional integrity of the estrogen response pathway could be useful.Proteases and their inhibitors have been a subject of interest in BC since they were demonstrated to play a role in invasiveness, tumor spread and metastatic processes. [4][5][6][7] Particularly during the last years, two serine proteases, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), were recognized, with level of evidence I (LOE I), as biomarkers of the prognosis, in the recent panel expert consensus.3 These proteases are involved in collagenase IV destruction and the degradation of the basement membrane and therefore promote the metastatic process.
8,9Background: Tumor-related proteases such as urokinase-type plasminogen (upa), plasminogen activator inhibitor (paI-1) and cathepsin D (cath-D) are involved in the prognosis of breast cancer (BC) and promote the metastatic process. We investigated the relationship between these proteases and their prognostic significance according to the eR status.Results: Quantitative levels of upa and paI-1 were higher in eR -patients (p < 0.001) whereas no difference was observed for cath-D levels in eR subsets (p = 0.96). In patients with a positive and highly positive eR status, a high cath-D level was associated with a poorer prognosis. patients in the highly positive eR group experienced poorer survival in the group with a high paI-1 level compared to the group with a low paI-1 level. In eR + patients, cath-D (p = 0.02) and the tumor size (p = 0.03) were independent factors for Os.Methods: upa, paI-1 and cath-D levels were prospectively measured in tumor from 316 patients with primary BC. The distribution and relationship between these proteases and eR subsets were analyzed as well as the prognostic significance.Conclusion: The prognostic significance of proteases is modulated by the eR status. Cath-D and paI-1 could identify a high-risk group with an adverse outcome in eR + patients.