Abstract
1065 Background: The benefit of the anti-VEGF antibody BEV—despite its confirmed activity with chemotherapy—remains unclear in BC pts. This may reflect that its benefit is limited to an unknown subset of BC pts. Methods: We previously reported the outcome and circulating biomarker data of a phase II study of neoadjuvant BEV with chemotherapy in ER+ BC and TNBC pts (NCT00546156; ASCO 2012 abstr 1026). In the present study we evaluated tissue biomarkers after 1 run-in cycle of BEV treatment alone. Patients then received BEV with standard dose-dense doxorubicin/cyclophosphamide/paclitaxel. We analyzed the changes in tissue biomarkers in ER+ BC versus TNBC pts after BEV alone and their correlation with outcome at surgery. The primary endpoint was pathologic response, measured by the Miller-Payne (MP) score (MP5=pCR). Results: Mean MP score was 3.1 for ER+ BC pts versus 4 for TNBC pts (area under ROC=0.60, P<0.001). This supports the hypothesis that the activity of BEV with chemotherapy may depend on BC subtype. In TNBCs, BEV significantly decreased mean microvascular density (MVD) by 33% (p<0.05). MVD was inversely correlated with the fraction of tissue positive for the hypoxia marker CAIX post-BEV (p<0.01). Moreover, a high pre-treatment MVD correlated with an increase in CAIX+ fraction post-BEV (p<0.05). In addition, a drop in MVD associated with increased CAIX+ fraction post-BEV (p=0.05). Finally, high (>60%) pericyte coverage post-BEV—ie, more mature vessels—was inversely correlated with CAIX+ fraction (p<0.05). MP score was more favorable for TNBC pts with lower CAIX+ fraction at baseline (p=0.058) and post-BEV (p<0.05), and higher MVD at baseline (p<0.05) and post-BEV (p<0.05). In contrast, BEV reduced MVD non-significantly by 15% in ER+ BC (p=0.25). There was no correlation between MVD and CAIX+ fraction in ER+ BCs. In contradistinction to TNBC, in ER+ BCs the fraction of CAIX+ tumor was directly correlated with MP score (p<0.01). Conclusions: Our exploratory study suggests that vascular pruning post-BEV may reduce vascular function and increase hypoxia, and reduce the effectiveness of chemotherapy in TNBC. Clinical trial information: NCT00546156.
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