Evidence map›Paper›PMID 26578779›Full record

Trial reportProceedings of the National Academy of Sciences of the United States of America2015

Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients.

Sara M Tolaney, Yves Boucher, Dan G Duda, John D Martin, Giorgio Seano, Marek Ancukiewicz, William T Barry, Shom Goel, Johanna Lahdenrata, Steven J Isakoff and 8 more

Open access · bronzeAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed
10.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

154 citing papers in PubMed, 254 citations in OpenAlex.

  1. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
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  4. Phase II Study of TQB2450, a Novel PD-L1 Antibody, in Combination with Anlotinib in Patients with Locally Advanced or Metastatic Soft Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
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  20. Targeting breast tumor extracellular matrix and stroma utilizing nanoparticles.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review

94 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Sara M TolaneyDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02114;
Yves BoucherDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Dan G DudaDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
John D MartinDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;ORCID http://orcid.org/0000-0002-9828-8203
Giorgio SeanoDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Marek AncukiewiczDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
William T BarryDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02114;
Shom GoelDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02114; Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Johanna LahdenrataDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Steven J IsakoffDepartment of Hematology/Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Eren D YehDepartment of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02114;
Saloni R JainDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
Mehra GolshanDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02114;
Jane BrockDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02114;
Matija SnuderlDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
Eric P WinerDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02114;
Ian E KropDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02114; ikrop@partners.org jain@steele.mgh.harvard.edu.
Rakesh K JainDepartment of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; ikrop@partners.org jain@steele.mgh.harvard.edu.
Harvard University · USBrigham and Women's Hospital · US

Funding

Vascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2000 to 2016
$35.0M
Variation in Receptor Tyrosine Kinases and Breast Cancer RiskP50CA089393 · NCI · DANA-FARBER CANCER INSTITUTE · PI HARRIS, LYNDSAY NORINE · 2000 to 2009
$28.8M
Viral Vectors in Tumors: Effects of Taxol and RadiationR01CA098706 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES · 2003 to 2013
$2.8M
NCI NIH HHS 2P50 CA089393-08S2NCI NIH HHS P01 CA080124NCI NIH HHS P50 CA089393NCI NIH HHS R01 CA098706NCI NIH HHS R01CA098706
6 · The paper itself

Abstract

Preoperative 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, a marker 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.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorBreast NeoplasmsFemaleHumansMiddle AgedNeoadjuvant TherapyNeovascularization, PathologicBevacizumabBiomarkers, Tumorantiangiogenic therapycellular proliferationcirculating and tissue biomarkersPAM50 gene signature

Identifiers

PMID26578779
PMCPMC4655544
OpenAlexW1921704765

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.