Antiangiogenic and Antitumor Effects of Bevacizumab in Patients With Inflammatory and Locally Advanced Breast Cancer

Wedam, Suparna; Low, Jennifer A.; Yang, Sherry X.; Chow, Catherine; Choyke, Peter L.; Danforth, David N.; Hewitt, Stephen M.; Berman, Arlene; Steinberg, Seth M.; Liewehr, David J.; Plehn, Jonathan F.; Doshi, Arpi; Thomasson, Dave; McCarthy, Nicole; Koeppen, Hartmut; Sherman, Mark E.; Zujewski, Jo Anne; Camphausen, Kevin; Chen, Helen; Swain, Sandra M.

doi:10.1200/jco.2005.03.4645

Cited by 488 publications

(325 citation statements)

References 25 publications

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“…26 As such, there are currently several prospective studies evaluating inhibitors of angiogenesis (eg, bevacizumab) for the treatment of IBC. 27 A higher frequency of overexpression of human epidermal growth factor receptor 2 (HER2) among IBC tumors compared with non-IBC tumors has also been reported, 28,29 making HER2-directed targeted therapy with adjuvant trastuzumab important. Women In conclusion, in this large population-based study, we demonstrated that in the era of the use of anthracyclines and taxanes, survival differences between women with stage IIIB/C IBC and those with non-IBC LABC are still present, with differences observed early.…”

Section: Discussionmentioning

confidence: 99%

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early

Dawood

Ueno

Valero

et al. 2010

Cancer

126

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BACKGROUND: Significant improvements in the survival of women with breast cancer have been observed and are attributed to a multidisciplinary approach and the introduction of polychemotherapy and endocrine regimens. The objective of this population-based study was to determine whether women with inflammatory breast cancer (IBC) who received treatment in a modern era had a poorer survival compared those with non-IBC locally advanced breast cancer (LABC). METHODS: The Surveillance, Epidemiology, and End Results program registry was searched to identify women with stage IIIB/C breast cancer diagnosed between 2004 and 2007 who had undergone surgery and radiotherapy. Patients were categorized as either having IBC or non-IBC LABC according the sixth edition of the American Joint Committee on Cancer (AJCC) criteria. Breast cancer-specific survival (BCS) was estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Cox models were then fitted to compare the association between breast cancer type and BCS after adjusting for patient and tumor characteristics. RESULTS: A total of 828 (19.2%) women and 3476 (80.8%) women had stage IIIB/C IBC and non-IBC LABC, respectively. The median follow-up was 19 months. The 2-year BCS rate was 90% (95% confidence interval [95% CI], 88%-91%) for the entire cohort and 84% (95%CI, 80%-87%) and 91% (95%CI, 90%-91%) among women with IBC and non-IBC LABC, respectively. In the multivariable model, patients with IBC were found to have a 43% increased risk of death from breast cancer compared with patients with non-IBC LABC (hazard ratio, 1.43; 95%CI, 1.10-1.86 [P ¼ .008]). CONCLUSIONS: In the era of multidisciplinary management and anthracycline-based and taxane-based polychemotherapy regimens, women with IBC continue to have worse survival outcomes compared with those with non-IBC LABC.

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Section: Discussionmentioning

confidence: 99%

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early

Dawood

Ueno

Valero

et al. 2010

Cancer

126

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“…K trans reduction was increased following a further six cycles of bevacizumab with conventional chemotherapy. However changes in K trans did not predict response rate (RR) (Wedam et al, 2006). Several tyrosine kinase inhibitors, notably AG-013736 (Liu et al, 2005), BIBF1120 (Mross et al, 2005b) and AZD2171 (Drevs et al, 2005) have all shown dose-dependent reductions in K trans and IAUC without demonstrating clinical response.…”

Section: Biomarker Evidence Of Drug Effect -What Does It Mean?mentioning

confidence: 99%

“…In practice data are frequently suboptimal and can lead to trial data being excluded or of limited value (Eder et (Tables 1 and 2). Most were small cohort single-centre phase I trials in patients with advanced solid tumours, although a small number of phase II trials have incorporated DCE-MRI (Wedam et al, 2006). Marked variation in tumour size (Evelhoch et al, 2004), anatomy and pathophysiology and previous treatment (Morgan et al, 2003) have made data evaluation difficult and may have masked subtle drug effects, prompting a move towards stricter inclusion criteria (Morgan et al, 2003;Mross et al, 2005a;O'Dwyer et al, 2005) or using an intra-patient dose escalation design (Jayson et al, 2002;Stevenson et al, 2003).…”

Section: Data Qualitymentioning

confidence: 99%

DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents

et al. 2007

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Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is now frequently used in early clinical trial assessment of antiangiogenic and vascular disrupting compounds. Evidence of drug efficacy and dose-dependent response has been demonstrated with some angiogenesis inhibitors. This review highlights the critical issues that influence T 1 -weighted DCE-MRI data acquisition and analysis, identifies important areas for future development and reviews the clinical trial findings to date.

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“…The potential pleiotropic effects of anti-VEGF therapy is in part due to the fact that VEGF receptors are expressed not only on endothelial cells in tumors, but also on subsets of hematopoietic cells, stromal cells, in addition to malignant cells in certain human cancers (e.g. breast, brain, colorectal and pancreatic [11,[38][39][40]). The existing clinical data on the mechanisms of action of anti-VEGF therapy that have been suggested by preclinical studies [9,11,12] are discussed below.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

Duda

Batchelor

Willett

et al. 2007

Trends in Molecular Medicine

125

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Despite setbacks, the clinical development of antiangiogenic agents has accelerated remarkably over the past 3-4 years. Consequently, there are currently three direct inhibitors of the VEGF pathway approved for use in cancer therapy. Other agents that block the VEGF pathway are in advanced stages of clinical development and have shown promising results. With these exciting developments come crucial questions regarding the use of these new molecular-targeted agents, alone or in combination with standard cytotoxic or targeted agents. Importantly, the mechanisms of action of anti-VEGF therapy remain unknown. Here, we discuss several potential mechanisms of action such as tumor vascular normalization, bone marrow-derived cell recruitment blockade and cytostatic effects of anti-VEGF therapy. We review the current progress, the major stumbling blocks and the future directions for anti-cancer therapy using anti-VEGF agents, emphasizing clarification of the underlying molecular mechanisms of action and biomarker identification and validation.

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Antiangiogenic and Antitumor Effects of Bevacizumab in Patients With Inflammatory and Locally Advanced Breast Cancer

Abstract: Bevacizumab has inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumor cells.

Cited by 488 publications

References 25 publications

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early

DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

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