Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: Clinical and biological activity

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ≥10% T2-T4a-c, N0-N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70-95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, -82%, -62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity.

Original languageEnglish
Pages (from-to)1564-1571
Number of pages8
JournalBritish Journal of Cancer
Volume99
Issue number10
DOIs
Publication statusPublished - Nov 4 2008

Fingerprint

letrozole
Breast Neoplasms
Drug Therapy
Triptorelin Pamoate
Angiogenesis Inhibitors
Therapeutics
Combination Drug Therapy
Proteinuria
Venous Thrombosis
Endothelial Cells
Biomarkers
Hypertension
Bevacizumab

Keywords

  • Bevacizumab
  • Chemoendocrine therapy
  • Endocrine-responsive breast cancer
  • Preoperative therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{e3450fbec6ac46f093d3cc9d3f106682,
title = "Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: Clinical and biological activity",
abstract = "The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ≥10{\%} T2-T4a-c, N0-N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86{\%} (95{\%} CI, 70-95) and no pCR were observed; Ki67 was significantly decreased by 71{\%} (interquartile range, -82{\%}, -62{\%}). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity.",
keywords = "Bevacizumab, Chemoendocrine therapy, Endocrine-responsive breast cancer, Preoperative therapy",
author = "R. Torrisi and V. Bagnardi and A. Cardillo and F. Bertolini and E. Scarano and L. Orlando and P. Mancuso and A. Luini and A. Calleri and G. Viale and A. Goldhirsch and M. Colleoni",
year = "2008",
month = "11",
day = "4",
doi = "10.1038/sj.bjc.6604741",
language = "English",
volume = "99",
pages = "1564--1571",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer

T2 - Clinical and biological activity

AU - Torrisi, R.

AU - Bagnardi, V.

AU - Cardillo, A.

AU - Bertolini, F.

AU - Scarano, E.

AU - Orlando, L.

AU - Mancuso, P.

AU - Luini, A.

AU - Calleri, A.

AU - Viale, G.

AU - Goldhirsch, A.

AU - Colleoni, M.

PY - 2008/11/4

Y1 - 2008/11/4

N2 - The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ≥10% T2-T4a-c, N0-N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70-95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, -82%, -62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity.

AB - The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ≥10% T2-T4a-c, N0-N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70-95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, -82%, -62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity.

KW - Bevacizumab

KW - Chemoendocrine therapy

KW - Endocrine-responsive breast cancer

KW - Preoperative therapy

UR - http://www.scopus.com/inward/record.url?scp=55949102088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55949102088&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6604741

DO - 10.1038/sj.bjc.6604741

M3 - Article

C2 - 18941458

AN - SCOPUS:55949102088

VL - 99

SP - 1564

EP - 1571

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 10

ER -