uPA AND PAI-1 In Breast Cancer: Review Of Their Clinical Utility And Current Validation In The ProspectivE NNBC-3 TRIAL

Annecke, K; Schmitt, Manfred; Euler, U.; Zerm, M.; Paepke, D.; Paepke, Stefan; Minckwitz, Gϋnter von; Thomssen, Christoph; Harbeck, Nadia

doi:10.1016/s0065-2423(07)00002-9

Cited by 98 publications

(79 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, DECORIN was chosen to represent an activated stroma in the Farmer metagene, with high levels predictive of resistance to chemotherapy in ER À disease (23). High levels of PLAU and the corresponding protein u-PA, needed for breakdown of the extracellular matrix, have been associated with prediction of benefit of adjuvant chemotherapy and worse outcome (23,44), and in the present dataset a similar trend with a better outcome for low levels of PLAU was found. None of the stromal genes retained independent prognostic value in the multivariable models, which may be due to the strong correlation found with ER status.…”

Section: Discussionsupporting

confidence: 63%

Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease

Klintman

Buus

Cheang

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression. Experimental Design: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffin-embedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies. The paired t test was used for testing changes in gene expression, and Cox regression and penalized elastic-net Cox Regression for estimating HRs. Results: After NAC, 12 genes were significantly up- and 8 downregulated. Fourteen genes were significantly associated with time to recurrence in univariable analysis in residual disease. In a multivariable model, ACACB, CD3D, MKI67, and TOP2A added prognostic value independent of clinical ER−, PgR−, and HER2− status. In ER+/HER2− patients, ACACB, PAWR, and ERBB2 predicted outcome, whereas CD3D and PAWR were prognostic in ER−/HER2− patients. By use of elastic-net analysis, a 6-gene signature (ACACB, CD3D, DECORIN, ESR1, MKI67, PLAU) was identified adding prognostic value independent of ER, PgR, and HER2. Conclusions: Most of the tested genes were significantly enriched or depleted in response to NAC. Expression levels of genes representing proliferation, stromal activation, metabolism, apoptosis, stemcellness, immunologic response, and Ras–ERK activation predicted outcome in residual disease. The multivariable gene models identified could, if validated, be used to identify patients needing additional post-neoadjuvant treatment to improve prognosis. Clin Cancer Res; 22(10); 2405–16. ©2016 AACR.

show abstract

Section: Discussionsupporting

confidence: 63%

Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease

Klintman

Buus

Cheang

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…11,12 However, cath-D even if its potential interest in BC has been recognized, it did not reach LOE I. Effectively, in contrast to uPA and PAI whose prognostic significance as well as predictive utility were assessed in large studies, [13][14][15] no such analysis was performed for cath-D, particularly since Grøndahl-Hansen and colleagues showed the superior prognostic value of the uPA/ PAI-1 system. 16 The relationship between uPA, PAI-1 and cathD has been explored 17,18 but their relationship with the quantitative expression of ER has rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of tumor-related proteases as a function of the estrogen receptor status

Mazouni¹,

Romain²,

Bonnier³

et al. 2011

Cancer Biology & Therapy

View full text Add to dashboard Cite

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.

show abstract

“…Additionally, the Chemo N0 trial showed that nodenegative breast cancer patients with high uPA/PAI-1 levels benefit significantly from adjuvant chemotherapy with CMF [13,14]. In the ongoing NNBC-3 trial, optimal chemotherapy (anthracycline-taxane versus anthracycline-based) for patients with high uPA/PAI-1 levels is being evaluated and the results are eagerly awaited [26].…”

Section: Discussionmentioning

confidence: 99%

High levels of uPA and PAI-1 predict a good response to anthracyclines

Borštnar

Sadikov

Možina

et al. 2009

Breast Cancer Res Treat

View full text Add to dashboard Cite

uPA AND PAI-1 In Breast Cancer: Review Of Their Clinical Utility And Current Validation In The ProspectivE NNBC-3 TRIAL

Cited by 98 publications

References 43 publications

Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease

Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease

Prognostic significance of tumor-related proteases as a function of the estrogen receptor status

High levels of uPA and PAI-1 predict a good response to anthracyclines

Contact Info

Product

Resources

About