Baseline microvessel density predicts response to neoadjuvant bevacizumab treatment of locally advanced breast cancer

Sci Rep. 2021 Feb 9;11(1):3388. doi: 10.1038/s41598-021-81914-0.

Abstract

A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like (P ≤ 0.009) and triple negative phenotypes (P ≤ 0.041). pMVD and GMP did also associate with high-grade tumors (P ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Bevacizumab / administration & dosage*
  • Biopsy, Large-Core Needle
  • Breast Neoplasms* / blood supply
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Male
  • Microvascular Density*
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neovascularization, Pathologic* / drug therapy
  • Neovascularization, Pathologic* / pathology

Substances

  • Bevacizumab