PMID- 24292957
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20220409
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 143
IP  - 1
DP  - 2014 Jan
TI  - Phosphorylated VEGFR2 and hypertension: potential biomarkers to indicate 
      VEGF-dependency of advanced breast cancer in anti-angiogenic therapy.
PG  - 141-51
LID - 10.1007/s10549-013-2793-6 [doi]
AB  - The efficacy of anti-VEGF agents probably lies on VEGF-dependency. Apatinib, a 
      specific tyrosine kinase inhibitor that targets VEGF receptor 2, was assessed in 
      patients with advanced breast cancer (ABC) (ClinicalTrials.gov NCT01176669 and 
      NCT01653561). This substudy was to explore the potential biomarkers for 
      VEGF-dependency in apatinib-treated breast cancer. Eighty pretreated patients 
      received apatinib 750 or 500 mg/day orally in 4-week cycles. Circulating 
      biomarkers were measured using a multiplex assay, and tissue biomarkers were 
      identified with immunostaining. Baseline characteristics and adverse events (AEs) 
      were included in the analysis. Statistical confirmation of independent predictive 
      factors for anti-tumor efficacy was performed using Cox and Logistic regression 
      models. Median progression-free survival (PFS) was 3.8 months, and overall 
      survival (OS) was 10.6 months, with 17.5 % of objective response rate. Prominent 
      AEs (>/=60 %) were hypertension, hand-foot skin reaction (HFSR), and proteinuria. 
      Higher tumor phosphorylated VEGFR2 (p-VEGFR2) expressions (P = 0.001), higher 
      baseline serum soluble VEGFR2 (P = 0.031), hypertension (P = 0.011), and HFSR 
      (P = 0.018) were significantly related to longer PFS, whereas hypertension 
      (P = 0.002) and HFSR (P = 0.001) were also related to OS. Based on multivariate 
      analysis, only p-VEGFR2 (adjusted HR, 0.40; P = 0.013) and hypertension (adjusted 
      HR, 0.58; P = 0.038) were independent predictive factors for both PFS and 
      clinical benefit rate. Apatinib had substantial antitumor activity in ABC and 
      manageable toxicity. p-VEGFR2 and hypertension may be surrogate predictors of 
      VEGF-dependency of breast cancer, which may identify an anti-angiogenesis 
      sensitive population.
FAU - Fan, Minhao
AU  - Fan M
AD  - Department of Medical Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
FAU - Zhang, Jian
AU  - Zhang J
FAU - Wang, Zhonghua
AU  - Wang Z
FAU - Wang, Biyun
AU  - Wang B
FAU - Zhang, Qunlin
AU  - Zhang Q
FAU - Zheng, Chunlei
AU  - Zheng C
FAU - Li, Ting
AU  - Li T
FAU - Ni, Chen
AU  - Ni C
FAU - Wu, Zhenhua
AU  - Wu Z
FAU - Shao, Zhimin
AU  - Shao Z
FAU - Hu, Xichun
AU  - Hu X
LA  - eng
SI  - ClinicalTrials.gov/NCT01176669
SI  - ClinicalTrials.gov/NCT01653561
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20131201
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Pyridines)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 5S371K6132 (apatinib)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/adverse effects/therapeutic use
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Biomarkers/blood/metabolism
MH  - Breast Neoplasms/complications/drug therapy/metabolism/mortality/pathology
MH  - Cytokines/blood
MH  - Female
MH  - Humans
MH  - Hypertension/*etiology/*metabolism
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Phosphorylation
MH  - Pyridines/adverse effects/therapeutic use
MH  - Risk Factors
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Vascular Endothelial Growth Factor Receptor-2/*metabolism
EDAT- 2013/12/03 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/12/03 06:00
PHST- 2013/10/12 00:00 [received]
PHST- 2013/11/23 00:00 [accepted]
PHST- 2013/12/03 06:00 [entrez]
PHST- 2013/12/03 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - 10.1007/s10549-013-2793-6 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2014 Jan;143(1):141-51. doi: 10.1007/s10549-013-2793-6. 
      Epub 2013 Dec 1.