Malgorzata Banys-Paluchowski1, Isabell Witzel2, Sabine Riethdorf3, Klaus Pantel3, Brigitte Rack4, Wolfgang Janni4, Peter A Fasching5, Bahriye Aktas6, Sabine Kasimir-Bauer7, Andreas Hartkopf8, Erich-Franz Solomayer9, Tanja Fehm10, Volkmar Müller11. 1. Department of Gynecology and Obstetrics, Marienkrankenhaus Hamburg, Hamburg, Germany. 2. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. 3. Department of Tumour Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 4. Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany. 5. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. 6. Department of Gynecology, University Hospital Leipzig, Leipzig, Germany. 7. Department of Obstetrics and Gynecology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 8. Department of Obstetrics and Gynecology, University Hospital Tübingen, University of Tübingen, Tübingen, Germany. 9. Department of Gynecology and Obstetrics, Saarland University Hospital, Homburg/Saar, Germany. 10. Department of Obstetrics and Gynecology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. 11. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. vmueller@uke.de.
Abstract
PURPOSE: VEGF is one of the most important angiogenesis-stimulating cytokines and has been previously shown to be overexpressed in several solid cancers. The aim of the present study was to assess the clinical relevance of serum VEGF (sVEGF) in a large cohort of metastatic breast cancer patients and to explore the relationship between sVEGF and other blood-based biomarkers. METHODS: Two hundred fifty-three patients with metastatic breast cancer were enrolled in this prospective, multicentre study. Blood samples were collected before start of first-line or later-line treatment. sVEGF was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch and other biomarkers (EGFR, HER2, RAS p21, TIMP1, CAIX) by ELISA. RESULTS: Levels of sVEGF were determined in all patients, with a median concentration of 231 pg/ml. After a median follow-up of 19 months, median overall survival (OS) was 10.2 months in patients with sVEGF levels above the upper quartile (i.e. 367 pg/ml), while median OS has not been reached in patients with sVEGF < 367 pg/ml (p < 0.001). Median progression-free survival (PFS) was 4.8 months for patients with sVEGF ≥ 367 pg/ml versus 9.1 months with sVEGF levels < 367 pg/ml (p < 0.001). Patients with sVEGF levels ≥ 367 pg/ml and ≥ 5 CTCs had the shortest OS, while those with sVEGF < 367 pg/ml and non-elevated CTCs had the longest OS. CTCs, grading, line of therapy and RAS p21 were independent predictors of OS. sVEGF, line of therapy and CTCs were independent predictors of PFS in the multivariate analysis. CONCLUSIONS: Metastatic breast cancer patients with elevated levels of sVEGF have significantly worse clinical outcome. This finding supports the biological role of VEGF in breast cancer. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59722891 (DETECT).
PURPOSE:VEGF is one of the most important angiogenesis-stimulating cytokines and has been previously shown to be overexpressed in several solid cancers. The aim of the present study was to assess the clinical relevance of serum VEGF (sVEGF) in a large cohort of metastatic breast cancerpatients and to explore the relationship between sVEGF and other blood-based biomarkers. METHODS: Two hundred fifty-three patients with metastatic breast cancer were enrolled in this prospective, multicentre study. Blood samples were collected before start of first-line or later-line treatment. sVEGF was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch and other biomarkers (EGFR, HER2, RAS p21, TIMP1, CAIX) by ELISA. RESULTS: Levels of sVEGF were determined in all patients, with a median concentration of 231 pg/ml. After a median follow-up of 19 months, median overall survival (OS) was 10.2 months in patients with sVEGF levels above the upper quartile (i.e. 367 pg/ml), while median OS has not been reached in patients with sVEGF < 367 pg/ml (p < 0.001). Median progression-free survival (PFS) was 4.8 months for patients with sVEGF ≥ 367 pg/ml versus 9.1 months with sVEGF levels < 367 pg/ml (p < 0.001). Patients with sVEGF levels ≥ 367 pg/ml and ≥ 5 CTCs had the shortest OS, while those with sVEGF < 367 pg/ml and non-elevated CTCs had the longest OS. CTCs, grading, line of therapy and RAS p21 were independent predictors of OS. sVEGF, line of therapy and CTCs were independent predictors of PFS in the multivariate analysis. CONCLUSIONS:Metastatic breast cancerpatients with elevated levels of sVEGF have significantly worse clinical outcome. This finding supports the biological role of VEGF in breast cancer. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59722891 (DETECT).
Entities:
Keywords:
Biomarker; Breast cancer; Circulating tumor cell; Survival; VEGF
Authors: Othman Benchama; Sergiy Tyukhtenko; Michael S Malamas; Mark K Williams; Alexandros Makriyannis; Hava Karsenty Avraham Journal: Sci Rep Date: 2022-03-29 Impact factor: 4.379