Prognostic impact of the inclusion of uPA/PAI-1 for adjuvant treatment decision-making in ER+/Her2− pN0 early breast cancers
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Intermediate-risk early breast cancer (EBC) is a heterogeneous group in which adjuvant chemotherapy decision proves to be difficult. Clinical and pathological criteria are sometimes insufficient to determine the best therapeutic options, and validated biomarkers such as uPA/PAI-1, are needed to contribute to the decision-making. The objective of this study was to evaluate the clinical outcome of an unselected ER+/HER2− pN0 EBC cohort of patients in whom the routine clinical decision process included a prospective uPA/PAI-1 determination.
This monocentric retrospective study included 520 patients who underwent curative surgery in our institute between 2006 and 2011. Adjuvant therapeutic strategy was decided based on clinical–pathological data, altogether with a routine prospective determination of uPA/PAI-1 tumor levels using fresh, extemporaneously sampled tissue. We evaluated the correlation between uPA/PAI-1 levels, clinical-pathological variables, and the patient’s outcome (relapse-free survival, RFS, and overall survival, OS).
Median follow-up was 5.4 years. The 5- and 10-year RFS rates were ,respectively, 95 and 89%, and the five-year OS rate was 96.3%. Forty percent of tumors had low uPA/PAI-1 levels. Seventy-five percent of patients with low uPA/PAI-1 levels did not receive chemotherapy, when 25% did. Sixty percent of patients with high uPA and/or PAI-1 levels received chemotherapy, while 40% did not. No statistical significant correlation was found between the uPA/PAI-1 levels and RFS or OS.
The personalization of the patients’ treatment using uPA/PAI-1 tumor levels allows the reversion of the well-known poor prognostic impact of high uPA/PAI-1 levels and strongly supports the use of this biomarker in clinical practice.
KeywordsuPA/PAI-1 Adjuvant chemotherapy Breast cancer Tailoring
The authors thank Hélène de Forges, Ph.D., for editorial assistance.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Coates AS, Winer EP, Goldhirsch A et al (2015) Tailoring therapies—improving the management of early breast cancer: St gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol 26:1533–1546. doi: 10.1093/annonc/mdv221 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Harbeck N, Schmitt M, Meisner C et al (2013) Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients. Eur J Cancer 49(8):1825–1835. doi: 10.1016/j.ejca.2013.01.007 CrossRefPubMedGoogle Scholar
- 13.Harbeck N, Alt U, Berger U et al (2001) Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy. Clin Cancer Res 7:2757–2764PubMedGoogle Scholar
- 15.Denduluri N, Somerfield MR, Eisen A et al (2016) Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the cancer care ontario clinical practice guideline. J Clin Oncol 34:2416–2427. doi: 10.1200/JCO.2016.67.0182 CrossRefPubMedGoogle Scholar
- 16.Manders P, Tjan-Heijnen VCG, Span PN et al (2003) The complex between urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) independently predicts response to first-line endocrine therapy in advanced breast cancer. Thromb Haemost. doi: 10.1160/TH03-07-0467 CrossRefPubMedGoogle Scholar
- 27.Gligorov J, Pivot XB, Jacot W et al (2015) Prospective clinical utility study of the use of the 21-gene assay in adjuvant clinical decision making in women with estrogen receptor-positive early invasive breast cancer: results from the SWITCH study. Oncologist 20:873–879. doi: 10.1634/theoncologist.2014-0467 CrossRefPubMedPubMedCentralGoogle Scholar