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Published in: Breast Cancer Research and Treatment 1/2018

01-11-2018 | Clinical trial

The clinical relevance of serum vascular endothelial growth factor (VEGF) in correlation to circulating tumor cells and other serum biomarkers in patients with metastatic breast cancer

Authors: Malgorzata Banys-Paluchowski, Isabell Witzel, Sabine Riethdorf, Klaus Pantel, Brigitte Rack, Wolfgang Janni, Peter A. Fasching, Bahriye Aktas, Sabine Kasimir-Bauer, Andreas Hartkopf, Erich-Franz Solomayer, Tanja Fehm, Volkmar Müller

Published in: Breast Cancer Research and Treatment | Issue 1/2018

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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).
Appendix
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Literature
4.
go back to reference Linderholm B, Lindh B, Tavelin B, Grankvist K, Henriksson R (2000) p53 and vascular-endothelial-growth-factor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. Int J Cancer 89:51–62CrossRef Linderholm B, Lindh B, Tavelin B, Grankvist K, Henriksson R (2000) p53 and vascular-endothelial-growth-factor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. Int J Cancer 89:51–62CrossRef
5.
go back to reference Gasparini G (2000) Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 5:37–44CrossRef Gasparini G (2000) Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 5:37–44CrossRef
6.
go back to reference Eppenberger U, Kueng W, Schlaeppi JM, Roesel JL, Benz C, Mueller H, Matter A, Zuber M, Luescher K, Litschgi M, Schmitt M, Foekens JA, Eppenberger-Castori S (1998) Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 16:3129–3136. https://doi.org/10.1200/JCO.1998.16.9.3129 CrossRefPubMed Eppenberger U, Kueng W, Schlaeppi JM, Roesel JL, Benz C, Mueller H, Matter A, Zuber M, Luescher K, Litschgi M, Schmitt M, Foekens JA, Eppenberger-Castori S (1998) Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 16:3129–3136. https://​doi.​org/​10.​1200/​JCO.​1998.​16.​9.​3129 CrossRefPubMed
9.
go back to reference Linardou H, Kalogeras KT, Kronenwett R, Kouvatseas G, Wirtz RM, Zagouri F, Gogas H, Christodoulou C, Koutras AK, Samantas E, Pectasides D, Bafaloukos D, Fountzilas G (2012) The prognostic and predictive value of mRNA expression of vascular endothelial growth factor family members in breast cancer: a study in primary tumors of high-risk early breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial. Breast Cancer Res 14:R145. https://doi.org/10.1186/bcr3354 CrossRefPubMedPubMedCentral Linardou H, Kalogeras KT, Kronenwett R, Kouvatseas G, Wirtz RM, Zagouri F, Gogas H, Christodoulou C, Koutras AK, Samantas E, Pectasides D, Bafaloukos D, Fountzilas G (2012) The prognostic and predictive value of mRNA expression of vascular endothelial growth factor family members in breast cancer: a study in primary tumors of high-risk early breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial. Breast Cancer Res 14:R145. https://​doi.​org/​10.​1186/​bcr3354 CrossRefPubMedPubMedCentral
11.
go back to reference Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30:117–124CrossRef Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30:117–124CrossRef
12.
go back to reference Pivot X, Schneeweiss A, Verma S, Thomssen C, Passos-Coelho JL, Benedetti G, Ciruelos E, von Moos R, Chang HT, Duenne AA, Miles DW (2011) Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: results from AVADO. Eur J Cancer 47:2387–2395. https://doi.org/10.1016/j.ejca.2011.06.018 CrossRefPubMed Pivot X, Schneeweiss A, Verma S, Thomssen C, Passos-Coelho JL, Benedetti G, Ciruelos E, von Moos R, Chang HT, Duenne AA, Miles DW (2011) Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: results from AVADO. Eur J Cancer 47:2387–2395. https://​doi.​org/​10.​1016/​j.​ejca.​2011.​06.​018 CrossRefPubMed
13.
go back to reference Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676CrossRef Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676CrossRef
14.
go back to reference Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G (2014) Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol 15:1351–1360. https://doi.org/10.1016/S1470-2045(14)70444-9 CrossRefPubMed Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G (2014) Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol 15:1351–1360. https://​doi.​org/​10.​1016/​S1470-2045(14)70444-9 CrossRefPubMed
15.
go back to reference Baselga J, Zamagni C, Gomez P, Bermejo B, Nagai S, Melichar B, Chan A, Mangel L, Bergh J, Costa FP, Gomez HL, Gradishar W, Hudis C, Rapoport B, Roche H, Maeda P, Huang L, Zhang J, Schwartzberg LS (2014) A phase III randomized, double-blind, trial comparing sorafenib plus capecitabine versus placebo plus capecitabine in the treatment of locally advanced breast cancer (ESMO 2014). Ann Oncol 25:1–41CrossRef Baselga J, Zamagni C, Gomez P, Bermejo B, Nagai S, Melichar B, Chan A, Mangel L, Bergh J, Costa FP, Gomez HL, Gradishar W, Hudis C, Rapoport B, Roche H, Maeda P, Huang L, Zhang J, Schwartzberg LS (2014) A phase III randomized, double-blind, trial comparing sorafenib plus capecitabine versus placebo plus capecitabine in the treatment of locally advanced breast cancer (ESMO 2014). Ann Oncol 25:1–41CrossRef
16.
go back to reference Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, Kaklamani V, Stepanski EJ, Rugo HS, Wang W, Bell-McGuinn K, Kirshner JJ, Eisenberg P, Emanuelson R, Keaton M, Levine E, Medgyesy DC, Qamar R, Starr A, Ro SK, Lokker NA, Hudis CA (2013) Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res 19:2745–2754. https://doi.org/10.1158/1078-0432.CCR-12-3177 CrossRefPubMed Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, Kaklamani V, Stepanski EJ, Rugo HS, Wang W, Bell-McGuinn K, Kirshner JJ, Eisenberg P, Emanuelson R, Keaton M, Levine E, Medgyesy DC, Qamar R, Starr A, Ro SK, Lokker NA, Hudis CA (2013) Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res 19:2745–2754. https://​doi.​org/​10.​1158/​1078-0432.​CCR-12-3177 CrossRefPubMed
17.
go back to reference Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C (2012) First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol 30:921–929. https://doi.org/10.1200/JCO.2011.35.7376 CrossRefPubMed Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C (2012) First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol 30:921–929. https://​doi.​org/​10.​1200/​JCO.​2011.​35.​7376 CrossRefPubMed
18.
go back to reference Heer K, Kumar H, Read JR, Fox JN, Monson JR, Kerin MJ (2001) Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin Cancer Res 7:3491–3494PubMed Heer K, Kumar H, Read JR, Fox JN, Monson JR, Kerin MJ (2001) Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin Cancer Res 7:3491–3494PubMed
19.
go back to reference Adams J, Carder PJ, Downey S, Forbes MA, MacLennan K, Allgar V, Kaufman S, Hallam S, Bicknell R, Walker JJ, Cairnduff F, Selby PJ, Perren TJ, Lansdown M, Banks RE (2000) Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res 60:2898–2905PubMed Adams J, Carder PJ, Downey S, Forbes MA, MacLennan K, Allgar V, Kaufman S, Hallam S, Bicknell R, Walker JJ, Cairnduff F, Selby PJ, Perren TJ, Lansdown M, Banks RE (2000) Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res 60:2898–2905PubMed
21.
23.
go back to reference Banys-Paluchowski M, Fehm T, Janni W, Aktas B, Fasching PA, Kasimir-Bauer S, Milde-Langosch K, Pantel K, Rack B, Riethdorf S, Solomayer EF, Witzel I, Müller V (2018) Elevated serum RAS p21 is an independent prognostic factor in metastatic breast cancer. BMC Cancer, 18:541CrossRef Banys-Paluchowski M, Fehm T, Janni W, Aktas B, Fasching PA, Kasimir-Bauer S, Milde-Langosch K, Pantel K, Rack B, Riethdorf S, Solomayer EF, Witzel I, Müller V (2018) Elevated serum RAS p21 is an independent prognostic factor in metastatic breast cancer. BMC Cancer, 18:541CrossRef
24.
go back to reference Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, Aktas B, Kasimir-Bauer S, Zeitz J, Pantel K, Fehm T (2011) Prospective evaluation of serum tissue inhibitor of metalloproteinase 1 and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer. Breast Cancer Res 13:R71. https://doi.org/10.1186/bcr2916 CrossRefPubMedPubMedCentral Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, Aktas B, Kasimir-Bauer S, Zeitz J, Pantel K, Fehm T (2011) Prospective evaluation of serum tissue inhibitor of metalloproteinase 1 and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer. Breast Cancer Res 13:R71. https://​doi.​org/​10.​1186/​bcr2916 CrossRefPubMedPubMedCentral
26.
go back to reference Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V (2013) AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol 31:1719–1725. https://doi.org/10.1200/JCO.2012.44.7912 CrossRefPubMed Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V (2013) AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol 31:1719–1725. https://​doi.​org/​10.​1200/​JCO.​2012.​44.​7912 CrossRefPubMed
28.
go back to reference Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O’Shaughnessy J (2017) Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer 70:146–155. https://doi.org/10.1016/j.ejca.2016.09.024 CrossRefPubMed Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O’Shaughnessy J (2017) Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer 70:146–155. https://​doi.​org/​10.​1016/​j.​ejca.​2016.​09.​024 CrossRefPubMed
30.
go back to reference Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791CrossRef Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791CrossRef
32.
go back to reference Kondo S, Asano M, Matsuo K, Ohmori I, Suzuki H (1994) Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients. Biochim Biophys Acta 1221:211–214CrossRef Kondo S, Asano M, Matsuo K, Ohmori I, Suzuki H (1994) Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients. Biochim Biophys Acta 1221:211–214CrossRef
33.
go back to reference Salven P, Manpaa H, Orpana A, Alitalo K, Joensuu H (1997) Serum vascular endothelial growth factor is often elevated in disseminated cancer. Clin Cancer Res 3:647–651PubMed Salven P, Manpaa H, Orpana A, Alitalo K, Joensuu H (1997) Serum vascular endothelial growth factor is often elevated in disseminated cancer. Clin Cancer Res 3:647–651PubMed
34.
go back to reference Salven P, Perhoniemi V, Tykka H, Maenpaa H, Joensuu H (1999) Serum VEGF levels in women with a benign breast tumor or breast cancer. Breast Cancer Res Treat 53:161–166CrossRef Salven P, Perhoniemi V, Tykka H, Maenpaa H, Joensuu H (1999) Serum VEGF levels in women with a benign breast tumor or breast cancer. Breast Cancer Res Treat 53:161–166CrossRef
35.
go back to reference Coskun U, Gunel N, Toruner FB, Sancak B, Onuk E, Bayram O, Cengiz O, Yilmaz E, Elbeg S, Ozkan S (2003) Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer. Neoplasma 50:41–46PubMed Coskun U, Gunel N, Toruner FB, Sancak B, Onuk E, Bayram O, Cengiz O, Yilmaz E, Elbeg S, Ozkan S (2003) Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer. Neoplasma 50:41–46PubMed
36.
go back to reference Iovino F, Ferraraccio F, Orditura M, Antoniol G, Morgillo F, Cascone T, Diadema MR, Aurilio G, Santabarbara G, Ruggiero R, Belli C, Irlandese E, Fasano M, Ciardiello F, Procaccini E, Lo Schiavo F, Catalano G, De Vita F (2008) Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer. Cancer Invest 26:250–255. https://doi.org/10.1080/07357900701560612 CrossRefPubMed Iovino F, Ferraraccio F, Orditura M, Antoniol G, Morgillo F, Cascone T, Diadema MR, Aurilio G, Santabarbara G, Ruggiero R, Belli C, Irlandese E, Fasano M, Ciardiello F, Procaccini E, Lo Schiavo F, Catalano G, De Vita F (2008) Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer. Cancer Invest 26:250–255. https://​doi.​org/​10.​1080/​0735790070156061​2 CrossRefPubMed
39.
go back to reference Sengupta K, Banerjee S, Saxena N, Banerjee SK (2003) Estradiol-induced vascular endothelial growth factor-A expression in breast tumor cells is biphasic and regulated by estrogen receptor-alpha dependent pathway. Int J Oncol 22:609–614PubMed Sengupta K, Banerjee S, Saxena N, Banerjee SK (2003) Estradiol-induced vascular endothelial growth factor-A expression in breast tumor cells is biphasic and regulated by estrogen receptor-alpha dependent pathway. Int J Oncol 22:609–614PubMed
42.
go back to reference Rocca A, Cancello G, Bagnardi V, Sandri MT, Torrisi R, Zorzino L, Viale G, Pietri E, Veronesi P, Dellapasqua S, Ferrucci F, Luini A, Johansson H, Ghisini R, Goldhirsch A, Colleoni M (2009) Perioperative serum VEGF and extracellular domains of EGFR and HER2 in early breast cancer. Anticancer Res 29:5111–5119PubMed Rocca A, Cancello G, Bagnardi V, Sandri MT, Torrisi R, Zorzino L, Viale G, Pietri E, Veronesi P, Dellapasqua S, Ferrucci F, Luini A, Johansson H, Ghisini R, Goldhirsch A, Colleoni M (2009) Perioperative serum VEGF and extracellular domains of EGFR and HER2 in early breast cancer. Anticancer Res 29:5111–5119PubMed
43.
go back to reference Lam SW, Nota NM, Jager A, Bos MM, van den Bosch J, van der Velden AM, Portielje JE, Honkoop AH, van Tinteren H, Boven E (2016) Angiogenesis- and hypoxia-associated proteins as early indicators of the outcome in patients with metastatic breast cancer given first-line bevacizumab-based therapy. Clin Cancer Res 22:1611–1620. https://doi.org/10.1158/1078-0432.ccr-15-1005 CrossRefPubMed Lam SW, Nota NM, Jager A, Bos MM, van den Bosch J, van der Velden AM, Portielje JE, Honkoop AH, van Tinteren H, Boven E (2016) Angiogenesis- and hypoxia-associated proteins as early indicators of the outcome in patients with metastatic breast cancer given first-line bevacizumab-based therapy. Clin Cancer Res 22:1611–1620. https://​doi.​org/​10.​1158/​1078-0432.​ccr-15-1005 CrossRefPubMed
44.
go back to reference Pectasides D, Papaxoinis G, Kotoula V, Fountzilas H, Korantzis I, Koutras A, Dimopoulos AM, Papakostas P, Aravantinos G, Varthalitis I, Kosmidis P, Skarlos D, Bournakis E, Bafaloukos D, Kalofonos HP, Kalogeras KT, Fountzilas G (2012) Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: a Hellenic Cooperative Oncology Group (HeCOG) study. Oncol Rep 27:216–224. https://doi.org/10.3892/or.2011.1504 CrossRefPubMed Pectasides D, Papaxoinis G, Kotoula V, Fountzilas H, Korantzis I, Koutras A, Dimopoulos AM, Papakostas P, Aravantinos G, Varthalitis I, Kosmidis P, Skarlos D, Bournakis E, Bafaloukos D, Kalofonos HP, Kalogeras KT, Fountzilas G (2012) Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: a Hellenic Cooperative Oncology Group (HeCOG) study. Oncol Rep 27:216–224. https://​doi.​org/​10.​3892/​or.​2011.​1504 CrossRefPubMed
45.
go back to reference Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP (2008) VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res 14:7871–7877. https://doi.org/10.1158/1078-0432.CCR-08-0593 CrossRefPubMed Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP (2008) VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res 14:7871–7877. https://​doi.​org/​10.​1158/​1078-0432.​CCR-08-0593 CrossRefPubMed
46.
go back to reference Arisato T, Hashiguchi T, Sarker KP, Arimura K, Asano M, Matsuo K, Osame M, Maruyama I (2003) Highly accumulated platelet vascular endothelial growth factor in coagulant thrombotic region. J Thromb Haemost 1:2589–2593CrossRef Arisato T, Hashiguchi T, Sarker KP, Arimura K, Asano M, Matsuo K, Osame M, Maruyama I (2003) Highly accumulated platelet vascular endothelial growth factor in coagulant thrombotic region. J Thromb Haemost 1:2589–2593CrossRef
47.
go back to reference Werther K, Christensen IJ, Nielsen HJ (2002) Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets. Scand J Clin Lab Invest 62:343–350CrossRef Werther K, Christensen IJ, Nielsen HJ (2002) Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets. Scand J Clin Lab Invest 62:343–350CrossRef
49.
go back to reference Skerenova M, Mikulova V, Capoun O, Zima T, Tesarova P (2017) Circulating tumor cells and serum levels of MMP-2, MMP-9 and VEGF as markers of the metastatic process in patients with high risk of metastatic progression. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 161:272–280. https://doi.org/10.5507/bp.2017.022 CrossRefPubMed Skerenova M, Mikulova V, Capoun O, Zima T, Tesarova P (2017) Circulating tumor cells and serum levels of MMP-2, MMP-9 and VEGF as markers of the metastatic process in patients with high risk of metastatic progression. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 161:272–280. https://​doi.​org/​10.​5507/​bp.​2017.​022 CrossRefPubMed
51.
go back to reference Pineda E, Salud A, Vila-Navarro E, Safont MJ, Llorente B, Aparicio J, Vera R, Escudero P, Casado E, Bosch C, Bohn U, Perez-Carrion R, Carmona A, Ayuso JR, Ripolles T, Bouzas R, Gironella M, Garcia-Albeniz X, Feliu J, Maurel J (2017) Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09 – 01) trial. Tumour Biol. https://doi.org/10.1177/1010428317705509 CrossRefPubMed Pineda E, Salud A, Vila-Navarro E, Safont MJ, Llorente B, Aparicio J, Vera R, Escudero P, Casado E, Bosch C, Bohn U, Perez-Carrion R, Carmona A, Ayuso JR, Ripolles T, Bouzas R, Gironella M, Garcia-Albeniz X, Feliu J, Maurel J (2017) Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09 – 01) trial. Tumour Biol. https://​doi.​org/​10.​1177/​1010428317705509​ CrossRefPubMed
53.
go back to reference Rogers CA, Scott LJ, Reeves BC, Phil D, Downes S, Lotery AJ, Dick AD, Chakravarthy U (2018) Serum vascular endothelial growth factor levels in the IVAN trial; relationships with drug, dosing, and systemic serious adverse events. Ophthalmology Retina 2:118–127CrossRef Rogers CA, Scott LJ, Reeves BC, Phil D, Downes S, Lotery AJ, Dick AD, Chakravarthy U (2018) Serum vascular endothelial growth factor levels in the IVAN trial; relationships with drug, dosing, and systemic serious adverse events. Ophthalmology Retina 2:118–127CrossRef
56.
go back to reference Muller V, Witzel I, Pantel K, Krenkel S, Luck HJ, Neumann R, Keller T, Dittmer J, Janicke F, Thomssen C (2006) Prognostic and predictive impact of soluble epidermal growth factor receptor (sEGFR) protein in the serum of patients treated with chemotherapy for metastatic breast cancer. Anticancer Res 26:1479–1487PubMed Muller V, Witzel I, Pantel K, Krenkel S, Luck HJ, Neumann R, Keller T, Dittmer J, Janicke F, Thomssen C (2006) Prognostic and predictive impact of soluble epidermal growth factor receptor (sEGFR) protein in the serum of patients treated with chemotherapy for metastatic breast cancer. Anticancer Res 26:1479–1487PubMed
58.
go back to reference Witzel I, Loibl S, von Minckwitz G, Eidtmann H, Fehm T, Khandan F, Schmatloch S, Hauschild M, Bischoff J, Fasching PA, Mau C, Schem C, Rack B, Meinhold-Heerlein I, Liedtke C, Karn T, Huober J, Zu Eulenburg C, Issa-Nummer Y, Untch M, Muller V (2012) Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab: a translational project in the neoadjuvant GeparQuinto trial. Br J Cancer 107:956–960. https://doi.org/10.1038/bjc.2012.353 CrossRefPubMedPubMedCentral Witzel I, Loibl S, von Minckwitz G, Eidtmann H, Fehm T, Khandan F, Schmatloch S, Hauschild M, Bischoff J, Fasching PA, Mau C, Schem C, Rack B, Meinhold-Heerlein I, Liedtke C, Karn T, Huober J, Zu Eulenburg C, Issa-Nummer Y, Untch M, Muller V (2012) Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab: a translational project in the neoadjuvant GeparQuinto trial. Br J Cancer 107:956–960. https://​doi.​org/​10.​1038/​bjc.​2012.​353 CrossRefPubMedPubMedCentral
59.
60.
go back to reference Erman H, Gelisgen R, Cengiz M, Tabak O, Erdenen F, Uzun H (2016) The association of vascular endothelial growth factor, metalloproteinases and their tissue inhibitors with cardiovascular risk factors in the metabolic syndrome. Eur Rev Med Pharmacol Sci 20:1015–1022PubMed Erman H, Gelisgen R, Cengiz M, Tabak O, Erdenen F, Uzun H (2016) The association of vascular endothelial growth factor, metalloproteinases and their tissue inhibitors with cardiovascular risk factors in the metabolic syndrome. Eur Rev Med Pharmacol Sci 20:1015–1022PubMed
62.
go back to reference Kim YB, Han JY, Kim TS, Kim PS, Chu YC (2000) Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma. J Gastroenterol Hepatol 15:1393–1399CrossRef Kim YB, Han JY, Kim TS, Kim PS, Chu YC (2000) Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma. J Gastroenterol Hepatol 15:1393–1399CrossRef
Metadata
Title
The clinical relevance of serum vascular endothelial growth factor (VEGF) in correlation to circulating tumor cells and other serum biomarkers in patients with metastatic breast cancer
Authors
Malgorzata Banys-Paluchowski
Isabell Witzel
Sabine Riethdorf
Klaus Pantel
Brigitte Rack
Wolfgang Janni
Peter A. Fasching
Bahriye Aktas
Sabine Kasimir-Bauer
Andreas Hartkopf
Erich-Franz Solomayer
Tanja Fehm
Volkmar Müller
Publication date
01-11-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4882-z

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