We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Preliminary Communication

Prognostic impact of the inclusion of uPA/PAI-1 tumor levels in the current adjuvant treatment decision-making for early breast cancer

    Haïdar Saadoun

    Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France

    ,
    Pierre-Jean Lamy

    Department of Biology & Oncogenetics, Montpellier Cancer Institute, Montpellier, France

    ,
    Simon Thezenas

    Department of Biostatistics, Montpellier Cancer Institute, Montpellier, France

    ,
    Stéphane Pouderoux

    Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France

    ,
    Frédéric Bibeau

    Department of Pathology, Montpellier Cancer Institute, Montpellier, France

    ,
    Frédéric Montels

    Department of Biology & Oncogenetics, Montpellier Cancer Institute, Montpellier, France

    ,
    Gilles Romieu

    Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France

    ,
    Pierre-Emmanuel Colombo

    Department of Surgical Oncology, Montpellier Cancer Institute, Montpellier, France

    ,
    Marian Gutowski

    Department of Surgical Oncology, Montpellier Cancer Institute, Montpellier, France

    &
    William Jacot

    * Author for correspondence

    Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France.

    Published Online:https://doi.org/10.2217/fon.13.177

    ABSTRACT Aims: Following the introduction of new adjuvant therapies we wanted to reappraise the prognostic and predictive value of uPA/PAI-1 in early breast cancer. Patients & methods: This monocentric retrospective study included 652 patients who had curative surgery between 2006 and 2011 and adjuvant treatment decision-making, taking into account uPA/PAI-1 tumor levels. Results: uPA and PAI-1 levels were associated with classical clinicopathological parameters and adjuvant chemotherapy decision, but not with peritumoral vascular invasion (PVI; also known as peritumoral vascular emboli). HER2 overexpression, PVI and uPA/PAI-1 levels were not significantly associated with relapse-free survival in univariate analysis. In multivariate analysis, T stage, N stage and progesterone receptors were the only independent relapse-free survival predictive factors. Conclusion: The absence of an association between uPA/PAI-1 and PVI allows their concomitant consideration in adjuvant treatment discussion. The overall good prognosis of patients with high uPA/PAI-1 levels might be linked to the uPA/PAI-1 predictive value and the inclusion of these parameters in adjuvant guidelines.

    Papers of special note have been highlighted as: • of interest •• of considerable interest

    References

    • Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet365(9472),1687–1717 (2005).
    • Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann. Oncol.20(8),1319–1329 (2009).
    • Boyages J, Chua B, Taylor R et al. Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy. Br. J. Surg.89(6),789–796 (2002).
    • Harbeck N, Thomssen C. A new look at node-negative breast cancer. Oncologist16(Suppl. 1),51–60 (2011).
    • De Mascarel I, Bonichon F, Durand M et al. Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers. Eur. J. Cancer34(1),58–65 (1998).•• One of the founding publications regarding the prognostic role of peritumoral vascular invasion in early breast cancer.
    • Lee AH, Pinder SE, Macmillan RD et al. Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma. Eur. J. Cancer42(3),357–362 (2006).
    • Gasparini G, Weidner N, Bevilacqua P et al. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J. Clin. Oncol.12(3),454–466 (1994).
    • Ragage F, Debled M, Macgrogan G et al. Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer?. Cancer116(13),3093–3101 (2010).
    • Ejlertsen B, Jensen MB, Rank F et al. Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer. J. Natl Cancer Inst.101(10),729–735 (2009).
    • 10  Duffy MJ, Duggan C. The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer. Clin. Biochem.37(7),541–548 (2004).
    • 11  Andreasen PA, Kjoller L, Christensen L, Duffy MJ. The urokinase-type plasminogen activator system in cancer metastasis: a review. Int. J. Cancer72(1),1–22 (1997).
    • 12  Look MP, van Putten WL, Duffy MJ et al. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J. Natl Cancer Inst.94(2),116–128 (2002).•• Meta-analysis providing the more accurate evaluation of the prognostic impact of the uPA/PAI-1 complex in early breast cancer patients.
    • 13  Harris L, Fritsche H, Mennel R et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J. Clin. Oncol.25(33),5287–5312 (2007).• Evidence-based recommendations for the use of tumor markers in breast cancer care.
    • 14  Manders P, Tjan-Heijnen VC, Span PN et al. Predictive impact of urokinase-type plasminogen activator: plasminogen activator inhibitor type-1 complex on the efficacy of adjuvant systemic therapy in primary breast cancer. Cancer Res.64(2),659–664 (2004).• Addresses the predictive value of the uPA/PAI-1 complex in early breast cancer.
    • 15  Borstnar S, Sadikov A, Mozina B, Cufer T. High levels of uPA and PAI-1 predict a good response to anthracyclines. Breast Cancer Res. Treat121(3),615–624 (2010).
    • 16  Harbeck N, Kates RE, Look MP et al. Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (n = 3424). Cancer Res.62(16),4617–4622 (2002).
    • 17  Pritchard KI. High levels of uPA and PAI-1 predict a good response to anthracyclines. Breast Cancer Res. Treat121(3),625–626 (2010).
    • 18  De Witte JH, Sweep CG, Klijn JG et al. Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients. Br. J. Cancer79(7–8),1190–1198 (1999).
    • 19  Foekens JA, Schmitt M, van Putten WL et al. Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients. Cancer Res.52(21),6101–6105 (1992).
    • 20  van Diest PJ, van der Wall E, Baak JP. Prognostic value of proliferation in invasive breast cancer: a review. J. Clin. Pathol.57(7),675–681 (2004).
    • 21  Baak JP, Van Diest PJ, Janssen EA et al. Proliferation accurately identifies the high-risk patients among small, low-grade, lymph node-negative invasive breast cancers. Ann. Oncol.19(4),649–654 (2008).
    • 22  Jacot W, Gutowski M, Azria D, Romieu G. Adjuvant early breast cancer systemic therapies according to daily used technologies. Crit. Rev. Oncol. Hematol.82(3),361–369 (2012).
    • 23  Sweep CG, Geurts-Moespot J, Grebenschikov N et al. External quality assessment of trans-European multicentre antigen determinations (enzyme-linked immunosorbent assay) of urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in human breast cancer tissue extracts. Br. J. Cancer78(11),1434–1441 (1998).
    • 24  Janicke F, Prechtl A, Thomssen C et al. Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J. Natl Cancer Inst.93(12),913–920 (2001).•• Only mature randomized trial to date using a tissue biomarker assay in the adjuvant treatment decision process.
    • 25  Breast cancer; recommendations for clinical practice of Saint Paul de Vence. Oncologie9(9),593–644 (2007).
    • 26  Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet351(9114),1451–1467 (1998).
    • 27  Sundquist M, Thorstenson S, Brudin L, Wingren S, Nordenskjold B. Incidence and prognosis in early onset breast cancer. Breast11(1),30–35 (2002).
    • 28  Hery M, Delozier T, Ramaioli A et al. Natural history of node-negative breast cancer: are conventional prognostic factors predictors of time to relapse?. Breast11(5),442–448 (2002).
    • 29  Harbeck N, Kates RE, Schmitt M. Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. J. Clin. Oncol.20(4),1000–1007 (2002).