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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 10/2013

Open Access 01-10-2013 | Research Article

Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response

Authors: P. Sánchez-Rovira, M. A. Seguí, A. Llombart, E. Aranda, A. Antón, A. Sánchez, M. Lomas, A. Jaén, M. Fernández, I. Porras, E. Dalmau, S. Morales, J. de la Haba-Rodríguez

Published in: Clinical and Translational Oncology | Issue 10/2013

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Abstract

Purpose

The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored.

Methods

Patients with HER-negative operable stage II–III BC ≥2 cm were enrolled. Four cycles of AC (A 60 mg/m2 and C 600 mg/m2, every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m2, every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment.

Results

Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15–36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76–93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed.

Conclusion

This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.
Literature
1.
Ellis P, Smith I, Ashley S et al (1998) Clinical prognostic and predictive factors for primary chemotherapy in operable breast cancer. J Clin Oncol 16(1):107–114PubMed
2.
Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16(8):2672–2685PubMed
3.
Bear HD, Anderson S, Smith RE et al (2006) Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24(13):2019–2027PubMedCrossRef
4.
5.
Sweeney CJ, Miller KD, Sissons SE et al (2001) The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors. Cancer Res 61(8):3369–3372PubMed
6.
Baar J, Silverman P, Lyons J et al (2009) A vasculature-targeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers. Clin Cancer Res 15(10):3583–3590PubMedCrossRef
7.
Bahri S, Chen JH, Mehta RS et al (2009) Residual breast cancer diagnosed by MRI in patients receiving neoadjuvant chemotherapy with and without bevacizumab. Ann Surg Oncol 16(6):1619–1628PubMedCrossRef
8.
Balduzzi A, Montagna E, Bagnardi V et al (2009) Infusional fluorouracil, epirubicin, and cisplatin followed by weekly paclitaxel plus bevacizumab in locally advanced breast cancer with unfavorable prognostic features. Anticancer Drugs 20(3):197–203PubMedCrossRef
9.
Greil R, Moik M, Reitsamer R et al (2009) Neoadjuvant bevacizumab, docetaxel and capecitabine combination therapy for HER2/neu-negative invasive breast cancer: efficacy and safety in a phase II pilot study. Eur J Surg Oncol 35(10):1048–1054PubMedCrossRef
10.
Sanchez-Munoz A, Duenas-Garcia R, Jaen-Morago A et al (2010) Is it possible to increase pCR in the neoadjuvant treatment with a dose-dense/sequential combination?: results from a phase II Trial combining epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine ± trastuzumab in stage II and III breast cancer patients. Am J Clin Oncol 33(5):432–437PubMedCrossRef
11.
Torrisi R, Bagnardi V, Cardillo A et al (2008) Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity. Br J Cancer 99(10):1564–1571PubMedCrossRef
12.
Yang SX, Steinberg SM, Nguyen D, Wu TD, Modrusan Z, Swain SM (2008) Gene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer. Clin Cancer Res 14(18):5893–5899PubMedCrossRef
13.
Bear HD, Tang G, Rastogi P et al (2012) Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 366(4):310–320PubMedCrossRef
14.
von Minckwitz G, Eidtmann H, Rezai M et al (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366(4):299–309CrossRef
15.
Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216PubMedCrossRef
16.
Smith IC, Miller ID (2001) Issues involved in research into the neoadjuvant treatment of breast cancer. Anticancer Drugs 12(Suppl 1):S25–S29PubMed
17.
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10(1):1–10PubMedCrossRef
18.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2005) Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 97(16):1180–1184PubMedCrossRef
19.
Colleoni M, Viale G, Zahrieh D et al (2008) Expression of ER, PgR, HER1, HER2, and response: a study of preoperative chemotherapy. Ann Oncol 19(3):465–472PubMedCrossRef
20.
Fernandez-Morales LA, Segui MA, Andreu X et al (2007) Analysis of the pathologic response to primary chemotherapy in patients with locally advanced breast cancer grouped according to estrogen receptor, progesterone receptor, and HER2 status. Clin Breast Cancer 7(7):559–564PubMedCrossRef
21.
Guarneri V, Broglio K, Kau SW et al (2006) Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24(7):1037–1044PubMedCrossRef
22.
Keam B, Im SA, Kim HJ et al (2007) Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer. BMC Cancer 7:203PubMedCrossRef
23.
Liedtke C, Mazouni C, Hess KR et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281PubMedCrossRef
24.
Mehta RS (2008) Hormone receptor, grade, human epidermal growth factor receptor 2, and topoisomerase II as predictors of response to chemotherapy. J Clin Oncol 26(15):2596–2597PubMedCrossRef
25.
Rouzier R, Perou CM, Symmans WF et al (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11(16):5678–5685PubMedCrossRef
26.
Evans TR, Yellowlees A, Foster E et al (2005) Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study. J Clin Oncol 23(13):2988–2995PubMedCrossRef
27.
Heys SD, Hutcheon AW, Sarkar TK et al (2002) Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial. Clin Breast Cancer 3(Suppl 2):S69–S74PubMedCrossRef
28.
von Minckwitz G, Raab G, Caputo A et al (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23(12):2676–2685CrossRef
29.
Forero-Torres A, Saleh MN, Galleshaw JA et al (2010) Pilot trial of preoperative (neoadjuvant) letrozole in combination with bevacizumab in postmenopausal women with newly diagnosed estrogen receptor- or progesterone receptor-positive breast cancer. Clin Breast Cancer 10(4):275–280PubMedCrossRef
30.
Wedam SB, Low JA, Yang SX et al (2006) Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol 24(5):769–777PubMedCrossRef
Metadata
Title
Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response
Authors
P. Sánchez-Rovira
M. A. Seguí
A. Llombart
E. Aranda
A. Antón
A. Sánchez
M. Lomas
A. Jaén
M. Fernández
I. Porras
E. Dalmau
S. Morales
J. de la Haba-Rodríguez
Publication date
01-10-2013
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 10/2013
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1006-4

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