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

Clin Transl Oncol. 2013 Oct;15(10):810-7. doi: 10.1007/s12094-013-1006-4. Epub 2013 Feb 9.

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/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / drug therapy*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Preoperative Care
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Remission Induction
  • Taxoids / administration & dosage

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Docetaxel
  • Bevacizumab
  • Doxorubicin
  • Cyclophosphamide
  • Receptor, ErbB-2