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dc.contributor.authorTolaney, Sara
dc.contributor.authorBoucher, Yves
dc.contributor.authorDuda, Dan
dc.contributor.authorMartin, John
dc.contributor.authorSeano, Giorgio
dc.contributor.authorAncukiewicz, Marek
dc.contributor.authorBarry, William
dc.contributor.authorGoel, Shom
dc.contributor.authorLahdenrata, Johanna
dc.contributor.authorIsakoff, Steven
dc.contributor.authorYeh, Eren
dc.contributor.authorJain, Saloni
dc.contributor.authorGolshan, Mehra
dc.contributor.authorBrock, Jane
dc.contributor.authorSnuderl, Matija
dc.contributor.authorWiner, Eric
dc.contributor.authorKrop, Ian
dc.contributor.authorJain, Rakesh
dc.date.accessioned2019-10-05T03:27:50Z
dc.date.issued2015
dc.identifier.citationTolaney, Sara M., Yves Boucher, Dan G. Duda, John D. Martin, Giorgio Seano, Marek Ancukiewicz, William T. Barry, et al. 2015. “Role of Vascular Density and Normalization in Response to Neoadjuvant Bevacizumab and Chemotherapy in Breast Cancer Patients.” Proceedings of the National Academy of Sciences 112 (46): 14325–30. https://doi.org/10.1073/pnas.1518808112.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41482962*
dc.description.abstractPreoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN) BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR) BC [5/78 patients or 6% (95% CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, amarker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleRole of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorDuda, Dan Gabriel::c98e9e279162984be65d72fd1be7bde2::600
dc.date.available2019-10-05T03:27:50Z
dash.workflow.comments1Science Serial ID 92270
dc.identifier.doi10.1073/pnas.1518808112
dash.source.volume112;46
dash.source.page14325


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