Skip to main content

Advertisement

SpringerLink
Log in

Systemic Effects of Surgery: Quantitative Analysis of Circulating Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor Beta (TGF-β) in Patients with Breast Cancer Who Underwent Limited or Extended Surgery

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Background. To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-β). Patients and methods. We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D−1), at the end of surgical tumor removal (D0), and on 1st (D+1), 2nd (D+2) and 5th (D+5) day after surgery. Serum VEGF, bFGF and TGF-β levels were measured by the enzyme immunoassay method. Results. On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D+5) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-β at 24–48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery. Conclusions. Angiogenic cytokines perioperative levels could be increased on 5th day (D+5) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. SE Reid MW Kaufman S Murthy EF Scanlon (1997) ArticleTitlePerioperative stimulation of residual cancer cells promotes local and distant recurrence of breast cancer J Am Coll Surg 185 290–306 Occurrence Handle10.1016/S1072-7515(98)80005-7 Occurrence Handle9291410

    Article  PubMed  Google Scholar 

  2. EJ Battegay (1995) ArticleTitleAngiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects J Mol Med 73 333–346 Occurrence Handle10.1007/BF00192885 Occurrence Handle8520966

    Article  PubMed  Google Scholar 

  3. SU Orredson DR Knighton H Scheuenstuhl TK Hunt (1983) ArticleTitleA quantitative in vitro study of fibroblast and endothelial cell migration in response to serum and wound fluid J Surg Res 35 249–258 Occurrence Handle6887846

    PubMed  Google Scholar 

  4. NN Nissen PJ Polverini AE Koch MV Volin RL Gamelli LA DiPietro (1998) ArticleTitleVascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing Am J Pathol 152 1445–1452 Occurrence Handle9626049

    PubMed  Google Scholar 

  5. MJ Reed P Puolakkainen TF Lane D Dickerson P Bornstein EH Sage (1993) ArticleTitleDifferential expression of SPARC and thrombospondin-1 in wound repair: immunolocalization and in situ hybridization J␣Histochem Cytochem 41 1467–1477 Occurrence Handle8245406

    PubMed  Google Scholar 

  6. LA Di Pietro NN Nissen RL Gamelli AE Koch JM Pyle PJ ␣Polverini (1996) ArticleTitleThrombospondin 1 synthesis and function in wound repair Am J Pathol 148 1851–1860 Occurrence Handle8669471

    PubMed  Google Scholar 

  7. P Martin (1997) ArticleTitleWound healing–aiming for perfect skin regeneration Science (Wash. DC) 276 75–81 Occurrence Handle10.1126/science.276.5309.75

    Article  Google Scholar 

  8. NN Nissen PJ Polverini RL Gamelli LA DiPietro (1996) ArticleTitleBasic fibroblast growth factor mediates angiogenic activity in early surgical wounds Surgery (St. Louis) 119 457–465

    Google Scholar 

  9. LF Brown KT Yeo B Berse TK Yeo DR Senger HF Dvorak WL van de (1992) ArticleTitleExpression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing J Exp Med 176 1375–1379 Occurrence Handle10.1084/jem.176.5.1375 Occurrence Handle1402682

    Article  PubMed  Google Scholar 

  10. Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? The Lancet, 2001

  11. K Heer H Kumar JR Read JN Fox JRT Monson MJ Kerin (2001) ArticleTitleSerum vascular endothelial growth factor in breast cancer. Its relation with cancer type and estrogen receptor status Clin Cancer Res 7 3491–3494 Occurrence Handle11705867

    PubMed  Google Scholar 

  12. G Sliutz C Tempfer A Obermair C Dadak C Kainz (1995) ArticleTitleSerum evaluation of basic FGF in breast cancer patients Anticancer Res 15 IssueID6B 2675–2677 Occurrence Handle8669845

    PubMed  Google Scholar 

  13. FM Kong MS Anscher T Murase BD Abbott JD Iglehart RL Jirtle (1995) ArticleTitleElevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor Ann Surg 222(2) 155–162

    Google Scholar 

  14. Sancak B, Coskun U, Gunel N, Onuk E, Cihan A, Karamercan A, Yildirim Y, Ozkan S: No association between serum levels ofinsulin-like growth factor-I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery. Intern Med J 34(6): 310–315, 2004

    Google Scholar 

  15. E Hormbrey C Han A Roberts DA McGrouther AL Harris (2003) ArticleTitleThe relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis Clin Cancer Res 9 4332–4339 Occurrence Handle14555503

    PubMed  Google Scholar 

  16. MS O’Reilly T Boehm Y Shing N Fukai G Vasios WS Lane E Flynn JR Birkhead BR Olsen J Folkman (1997) ArticleTitleEndostatin: an endogenous inhibitor of angiogenesis and tumor growth Cell 88 277–285 Occurrence Handle10.1016/S0092-8674(00)81848-6 Occurrence Handle9008168

    Article  PubMed  Google Scholar 

  17. MS O’Reilly L Holmgren Y Shing C Chen RA Rosenthal Y Cao M Moses WS Lane EH Sage J Folkman (1994) ArticleTitleAngiostatin: a circulating endothelial cell inhibitor that suppresses angiogenesis and tumor growth Cold Spring Harb Symp Quant Biol 59 471–482 Occurrence Handle7587101

    PubMed  Google Scholar 

  18. MS O’Reilly L Holmgren Y Shing C Chen RA Rosenthal M Moses WS Lane Y Cao EH Sage J Folkman (1994) ArticleTitleAngiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma Cell 79 315–328 Occurrence Handle10.1016/0092-8674(94)90200-3 Occurrence Handle7525077

    Article  PubMed  Google Scholar 

  19. D Skipper MJ Jeffrey AJ Cooper I Taylor P Alexander (1988) ArticleTitlePreferential growth of bloodborne cancer cells in colonic anastomoses Br J Cancer 57 564–568 Occurrence Handle3408643

    PubMed  Google Scholar 

  20. GF Whalen DE Ingber (1989) ArticleTitleInhibition of tumor-cell attachment to extracellular matrix as a method for preventing tumor recurrence in a surgical wound Ann Surg 210 758–764 Occurrence Handle2686568

    PubMed  Google Scholar 

  21. DE Davies S Farmer J White PV Senior SL Warnes P Alexander (1994) ArticleTitleContribution of host-derived growth factors to in vivo growth of a transplantable murine mammary carcinoma Br J Cancer 70 263–269 Occurrence Handle8054274

    PubMed  Google Scholar 

  22. SM Murthy RA Goldschmidt LN Rao M Ammirati T Buchmann EF Scanlon (1989) ArticleTitleThe influence of surgical trauma on experimental metastasis Cancer (Phila.) 64 2035–2044

    Google Scholar 

  23. B Fisher ER Fisher (1959) ArticleTitleExperimental studies of factors influencing hepatic metastases. III. Effect of surgical trauma with special reference to liver injury Ann Surg 150 731–744 Occurrence Handle13823186

    PubMed  Google Scholar 

  24. N Gunduz B Fisher EA Saffer (1979) ArticleTitleEffect of surgical removal on the growth and kinetics of residual tumor Cancer Res 39 3861–3865 Occurrence Handle476622

    PubMed  Google Scholar 

  25. L Simpson-Herren AH Sanford JP Holmquist (1976) ArticleTitleEffects of surgery on the cell kinetics of residual tumor Cancer Treat Rep 60 1749–1760 Occurrence Handle1026333

    PubMed  Google Scholar 

  26. B Fisher N Gunduz J Coyle C Rudock E Saffer (1989) ArticleTitlePresence of a growth-stimulating factor in serum following primary tumor removal in mice Cancer Res 49 1996–2001 Occurrence Handle2702641

    PubMed  Google Scholar 

  27. E Blitstein-Willinger (1991) ArticleTitleThe role of growth factors in wound healing Skin Pharmacol 4 175–182 Occurrence Handle1768429

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, Clinical Pharmacology and New Drugs Development Unit, European Institute of Oncology, Via Ripamonti 435, 20141, Milano, Italy

    G. Curigliano, M. Colleoni, L. Orlando, E. Munzone, E. Pietri & A. Goldhirsch

  2. Clinical Pharmacology and New Drugs Development Unit, European Institute of Oncology, Italy

    G. Curigliano, G. Peruzzotti & F. de Braud

  3. Division of Plastic Surgery, European Institute of Oncology, Italy

    J. Y. Petit, A. Giraldo & S. Martella

  4. Laboratory of Haemato-Oncology, European Institute of Oncology, Italy

    F. Bertolini

  5. Division of Epidemiology, European Institute of Oncology, Italy

    S. Gandini

  6. Division of Senology, European Institute of Oncology, Milan, Italy

    A. Luini

Authors
  1. G. Curigliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Y. Petit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Bertolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Colleoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Peruzzotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. de Braud
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Gandini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Giraldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. Martella
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L. Orlando
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. E. Munzone
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E. Pietri
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. A. Luini
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A. Goldhirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Curigliano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Curigliano, G., Petit, J.Y., Bertolini, F. et al. Systemic Effects of Surgery: Quantitative Analysis of Circulating Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor Beta (TGF-β) in Patients with Breast Cancer Who Underwent Limited or Extended Surgery. Breast Cancer Res Treat 93, 35–40 (2005). https://doi.org/10.1007/s10549-005-3381-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-005-3381-1

Key words:

Search

Navigation