Impact of tumor angiogenic profile on the outcome of patients with metastatic breast carcinoma treated with weekly docetaxel.: a Hellenic Cooperative Oncology Group (HeCOG) study

• Helen P. Kourea ^[1] ; Vassiliki Kotoula ^{[2] [2]} ; Angelos Koutras ^[1] ; Zoi Alexopoulou ^[6] ; Irene Papaspirou ^[3] ; Dimosthenis V. Skarlos ^[7] ; Ioannis Efstratiou ^[8] ; Mattheos Bobos ^[2] ; Flora Zagouri ^[4] ; Pavlos Papakostas ^[9] ; Dimitrios Pectasides ^[10] ; Sofia Chrisafi ^[2] ; Ioannis Varthalitis ^[11] ; Gerasimos Aravantinos ^[12] ; Paris Kosmidis ^[5] ; Dimitrios Bafaloukos ^[13] ; Chrisoula D. Scopa ^[1] ; George Fountzilas ^{[2] [2]}
  1. [1] University of Patras

     University of Patras

     Dimos Patras, Grecia

     
  2. [2] Aristotle University of Thessaloniki

     Aristotle University of Thessaloniki

     Dimos Thessaloniki, Grecia

     
  3. [3] Alexandra Hospital

     Alexandra Hospital

     Dimos Athens, Grecia

     
  4. [4] National and Kapodistrian University of Athens

     National and Kapodistrian University of Athens

     Dimos Athens, Grecia

     
  5. [5] Hygeia Hospital

     Hygeia Hospital

     Dimos Athens, Grecia

     
  6. [6] Health Data Specialists Ltd, Athens
  7. [7] Second Department of Medical Oncology, “Metropolitan” Hospital, Piraeus
  8. [8] Department of Pathology, "Papageorgiou" Hospital, Thessalonik
  9. [9] Department of Medical Oncology, “Hippokration” Hospital, Athens
  10. [10] Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, Athens
  11. [11] Oncology Department, General Hospital of Chania, Crete
  12. [12] Second Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens
  13. [13] First Department of Medical Oncology, “Metropolitan” Hospital, Piraeus

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 30, Nº. 9, 2015, págs. 1129-1141
• Idioma: inglés
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• Resumen

  • Background: Metronomic taxane administration has putative antiangiogenic properties. Herein, we examined the baseline tumor angiogenic profile of patients with metastatic breast carcinoma (MBC) in a prospective-retrospective translational research study. The interplay between the angiogenic factors expressed in the tumors and their prognostic value in MBC were investigated. Patients and Methods: Tumor tissues from patients with MBC treated with weekly docetaxel (n=159) were examined by immunohistochemistry for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, VEGFR-3 and osteopontin (OPN) and by mRNA analysis for expression of VEGF-A, VEGFxxxa, VEGFxxxb, VEGF-C, thrombospondin-1 (THBS-1), hypoxia-inducible factor-1? (HIF-1?) and von Hippel-Lindau (VHL) genes. Associations between these parameters and outcome were statistically analyzed. Results: Statistically significant correlations were identified between almost all biomarkers examined in continuous form, particularly at the mRNA level: VEGF-A with VEGFxxxa (rho=0.70); VEGF-C with VEGFxxxa, VEGFxxxb and VHL (rho=0.51, 0.60 and 0.44 respectively); HIF-1? with VEGF-C and THBS1 (rho=0.48 and 0.45). High VEGF-A mRNA was associated with worse survival (p=0.0279) and marginally with progression free survival (PFS). Intratumoral co-expression of VEGFR-1 and VEGFR-2 proteins was associated with more favorable survival (p=0.0337). In multivariate analysis, only high VEGF-A mRNA levels retained their prognostic role for worse PFS and survival (PFS: HR=2.34, 95% CI=1.25-4.40, p=0.0080; survival: HR=3.15, 95% CI=1.48-6.72, p=0.0029). Conclusions: In MBC, this study confirms the adverse prognostic effect of high intratumoral VEGF-A mRNA and reveals the combined VEGFR-1/VEGFR-2 protein expression as a potentially favorable prognosticator, which merits further evaluation in larger studies