Abstract P6-09-28: Prognostic impact of the inclusion of uPA/PAI-1 in ER+/Her2- pN0 early breast cancer adjuvant treatments decision-making
Authors: Viala M , Alexandre M , Thézenas S , Lamy P-J , Bibeau F , Gutowski M , Colombo P-E , Romieu G , Jacot W , Guiu S 
Published: March 2017

Purpose: Intermediate-risk early breast cancer (EBC) is a heterogeneous group in which adjuvant chemotherapy decision prove to be difficult. Clinical and pathological criteria might be insufficient to determine the best therapeutic options for patients, and validated biomarkers are urgently needed to help decision making, such as the LOE-I uPA/PAI-1 biomarker. The aim of this study is to evaluate the clinical outcome of a large, unselected, ER+/HER2- pN0 EBC cohort of patients in whom the routine clinical decision process included a prospective uPA/PAI-1 determination.

Methods: This monocentric retrospective study included 520 ER+/HER2- pN0/M0 EBC patients who had curative surgery in our center between 2006 and 2011. Adjuvant therapeutic strategy was decided based on clinico-pathological data, altogether with a routine prospective determination of uPA/PAI-1 tumor levels. We evaluated the correlation between uPA/PAI-1 levels, classical clinico-pathological variables and the patient's outcome (relapse free survival, RFS; overall survival, OS).

Results: Median age was 54 years (range 27-85). 75% of tumors were classified T1, 25% T2 and above. We found 80.8% of ductal carcinomas, 12.3% of lobular carcinomas and 6.9% of other histological types. SBR grade 1-2 represented 82.5% of our cohort versus 17.5% of grade 3. Mitotic count was &lt;10 in 63.5% of cases, and ≥10 in 36.5%. Peri-tumoral invasion (PVI) was seen in 17% of tumors. Progesterone receptors (PR) were positive in 79.6% of cases. Median follow-up was 5.4 years. 5 and 10 years RFS were respectively 95% and 89% (n=33 local or metastatic relapse). 5 year OS was 96.3%. We found 40% of low uPA/PAI-1 levels, and 60% of high uPA and/or PAI-1 levels. By using uPA/PAI-1 levels in our adjuvant treatment decision-making, 75% of patients with low uPA/PAI-1 levels did not received chemotherapy and 60% of patients with high uPA and/or PAI-1 levels received chemotherapy. 98.3% of our patients received endocrine therapy as adjuvant treatment for at least 5 years. No statistical significant correlation was found between uPA/PAI-1 levels and RFS (p=0.3) or OS (p=0.28). In univariate analysis, tumor size (p=0.048; p=0.0694), histological grade (p=0.007; p=0.0142), PR status (p=0.001; p=0.0002) and mitotic count (p=0.0001; p=0.0001) were statistically correlated with RFS and OS, respectively. Using cox regression model, PR status (p&lt;0.003) and mitotic count (p&lt;0.001) appeared to be strongly correlated with RFS. No changes in significant variables were seen when the analyses were restricted to the grade 2 subgroup (n=339).

Conclusion: The individualization of 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 support the use of this LOE-I biomarker in clinical practice. PR status and mitotic activity remains independent major prognostic factors in optimally treated patients. The evaluation of the additional impact of multigene signature in this setting needs to be performed. Longer 10-years follow-up needs to be done in this ER+/HER2- subgroup, particularly to evaluate the risk of late relapse after endocrine therapy.

Citation Format: Viala M, Alexandre M, Thézenas S, Lamy P-J, Bibeau F, Gutowski M, Colombo P-E, Romieu G, Jacot W, Guiu S. Prognostic impact of the inclusion of uPA/PAI-1 in ER+/Her2- pN0 early breast cancer adjuvant treatments decision-making [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-28.