Abstract P5-08-45: The predictive potential of metastatic serum markers and circulating tumor cells in advanced HER2-positive breast cancer patients - Focused on CNS metastases
Authors: Mikulova V , Jancikova M , Tesarova P , Zima T 
Published: May 2016

Abstract
Introduction: We performed a prospective study of advanced HER2-positive breast cancer (HER2-aBC) patients in palliative Trastuzumab therapy. We studied the presence of circulating tumor cells in the peripheral blood and matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor (VEGF) levels in the blood serum. We correlated these known metastatic markers primarily with the development of central nervous system (CNS) metastases, a very serious risk factor in HER2-positive BC patients. Further, we correlated these markers with disease progression and overall survival.
Patients and Methods: Our study group comprised 44 women with HER2-aBC and 42 healthy volunteers. Eighty-three percent of patients had metastases, mostly visceral and bone. Twelve patients developed CNS metastases, 3 before and 9 after study enrollment.
An immunomagnetic separation (AdnaGen, Germany) from 5 ml of whole blood, PCR-based methods and an on-chip capillary electrophoresis was used for the determination of CTC presence in BC patients. MMP-2, MMP-9 and VEGF serum levels were determined by ELISAs (Quantikine, R&D System, USA) of patients' sera - aliquoted and frozen at -20°C.
Results: CTCs were determined in only 17% of HER2-aBC patients. CTC positive patients had significantly shorter overall survival (p=0.04). The patients' MMP-9 and VEGF serum levels did not significantly differ from the control group. MMP-2 serum levels were significantly higher in the CTC-positive patients (p=0.02) and in the patients with bone metastases (p&lt;0.01). The patients with an MMP-2 serum level exceeding the 344 ng/ml had a 53times higher risk of CNS metastases (specificity 97%, sensitivity 64%). The HER2-aBC patients already suffering from bone metastases with an MMP-2 serum level above 350 ng/ml had a 204times higher risk of developing CNS metastases (specificity 97%, sensitivity 86%).
Conclusion: The presence of CTCs in the blood of HER2-aBC is a negative prognostic marker for overall survival. The HER2-aBC patients with the highest risk of CNS metastases development are those with an MMP-2 serum level above 350 ng/ml and bone metastases present. Our results indicate MMP-2 serum level as a possible predictive marker for CNS metastases development. Since CNS metastases represent a very serious complication in HER2-aBC patients our findings warrant verification in a larger study on a more stratified patient group.
This work was supported by the Grant Agency of Charles University GAUK, 539512, PRVOUK-P-27/LF1/1 and RVO-VFN 64 165.
Citation Format: Mikulova V, Jancikova M, Tesarova P, Zima T. The predictive potential of metastatic serum markers and circulating tumor cells in advanced HER2-positive breast cancer patients - Focused on CNS metastases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-45.