Baseline microvascular density correlates with bevacizumab response in breast cancer patients
medwireNews: Only breast cancer patients with tumours that have high pretreatment microvascular density are likely to benefit from neoadjuvant bevacizumab therapy, suggest research findings published in the Proceedings of the National Academy of Sciences of the United States of America.
In this phase II trial, 99 patients with triple-negative or hormone receptor-positive breast cancer were given a single dose of neoadjuvant bevacizumab followed by standard doxorubicin/cyclophosphamide/paclitaxel chemotherapy together with bevacizumab, prior to undergoing surgery.
Among 52 evaluable participants, baseline total and patent microvascular density, where the latter refers to the density of open lumen vessels, were significantly associated with markers of treatment response, specifically residual cancer burden and Miller–Payne tumour regression scores.
Additionally, an increase in the density of pericyte-covered mature microvessels after bevacizumab monotherapy correlated with improved response, but the association was significant only in the seven patients with triple-negative disease and not in the 32 with hormone receptor-positive breast cancer.
The evaluation of markers of vascular normalisation in pre- and post-treatment biopsy samples provided a clue to the potential underlying mechanism. Bevacizumab significantly reduced tumour microvessel density, but did not affect the density of pericyte-covered mature vessels, characterised by αSMA positivity. Bevacizumab treatment also reduced the interstitial fluid pressure. Taken together, these findings suggest that the anti-angiogenic drug leads to vascular normalisation in breast cancer, the authors believe.
Therefore, they say that tumours with high microvessel density “might benefit from the pruning of certain vessels and increased function of the remaining, normalized vessels”. By contrast, they add, tumours with low microvessel density “might have their already limited number of vessels pruned, which would outweigh the benefit of increased function of normalized vessels”.
Author Rakesh Jain, from Massachusetts General Hospital and Harvard Medical School in Boston, USA, said in a press release: “Our findings provide the first direct evidence of a relationship between structural vascular normalization and the extent of tumor regression after neoadjuvant bevacizumab treatment in breast cancer”.
Fellow author Ian Krop, from Dana–Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, USA, added: “Our results potentially identify the breast cancer patient population most likely to benefit from combined bevacizumab/chemotherapy treatment and suggest that new strategies to increase perfusion without pruning immature vessels, possibly by targeting alternative angiogenic pathways, should be explored to improve the outcome of patients with poorly perfused tumors.”
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