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Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

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Summary

Purpose

To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose–dense sequential chemotherapy.

Patients and methods

From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (T) 250 mg/m2 followed by three cycles of “intensified” CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC.

Results

HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death.

Conclusions

For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.

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Acknowledgements

The authors wish to thank Mrs. Irene Grimani (MSc) HeCOG Data Office, Athens, for statistical analysis, Mrs. Evita Fragou HeCOG Data Office, Athens for monitoring the study, Mrs. Maria Moschoni, HeCOG Data Office, Athens, for data coordination and Mrs. Thalia Spinari HeCOG Data Office, Athens for secretarial assistance. This study was supported in part by a HeCOG research Grant (HE R_1097) and a grant for Hellenic Post Office.

Also the authors would like to thank the following pathologists who contributed with paraffin-embedded tissues for the present study: G. Kafiri, D. Vlachodimitropoulos, D. Tziortziotis, Ch. Vambouka, Th. Filippidis, Th. Toliou, J. Ghiconti, A. Zizi, K. Manoloudaki, G. Liapi, S. Nikolopoulou, E. Parassi, S. Mavropoulou, K. Gavriilidis, E. Molyvas, E. Eleftheriadis and I. Hatzibougias.

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Authors and Affiliations

  1. Aristotle University of Thessaloniki, School of Medicine, Thessaloniki,, Greece

    Ioannis Kostopoulos, Thomas Zaramboukas & George Fountzilas

  2. «Metaxas» Cancer Hospital, Piraeus, Greece

    Petroula Arapantoni-Dadioti

  3. «Laiko» General Hospital, University of Athens, School of Medicine, Athens, Greece

    Helen Gogas, Vasiliki Kyriakou & Christos Markopoulos

  4. «Hygeia» Hospital, Athens, Greece

    Savvas Papadopoulos

  5. University of Ioannina School of Medicine, Ioannina, Greece

    Vasiliki Malamou-Mitsi

  6. «Rio» Hospital, University of Patras School of Medicine, Rio, Patras, Greece

    Chrisoula D. Scopa

  7. «Alexandra» General Hospital, Athens, Greece

    Sofia Markaki & Meletios A. Dimopoulos

  8. Medical Center of Athens, Athens, Greece

    Evangelia Karagianni

  9. «Mitera» Maternity and Surgical Center, Athens, Greece

    Anastasia Margariti

  10. 6th Social Services Oncological Hospital, Athens, Greece

    Elisavet Kyrkou

  11. «Αttikon» Hospital, University of Athens School of Medicine, Athens, Greece

    Kitty Pavlakis & Dimitrios Pectasides

  12. «Papanikolaou» General Hospital, Thessaloniki, Greece

    Anna Skordalaki

  13. «Agii Anargiri» Cancer Hospital, Athens, Greece

    Antonia Bourli

  14. «Henry Dunant» Hospital, Athens, Greece

    Dimosthenis Skarlos

  15. Department of Medical Oncology, “PAPAGEORGIOU” Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki, Macedonia, Greece

    George Fountzilas

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  1. Ioannis Kostopoulos
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  2. Petroula Arapantoni-Dadioti
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Correspondence to George Fountzilas.

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Kostopoulos, I., Arapantoni-Dadioti, P., Gogas, H. et al. Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy. Breast Cancer Res Treat 96, 251–261 (2006). https://doi.org/10.1007/s10549-005-9062-2

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  • DOI: https://doi.org/10.1007/s10549-005-9062-2

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