title: A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial.
abstract: Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed.
  
  
  
  We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993-2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9-12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER-/PR-. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR.
  
  
  
  Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33-2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63-3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19-2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors.
  
  
  
  There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1.
authors.affiliation: Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, 9609 Medical Center Drive, Bethesda, MD, 20852, USA. falkr@mail.nih.gov.
authors.forename: Roni T
authors.identifier: 0000-0001-5398-761X
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Women and Children's Division, Department of Gynecology and Obstetrics, Oslo University Hospital, Ullevål, 0424, Oslo, Norway.
authors.forename: Annetine Cathrine
authors.initials: AC
authors.lastname: Staff
authors.affiliation: Clinical and Epidemiologic Research Laboratory, Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Bradwin
authors.affiliation: Deparments of Medicine, Obstetrics and Gynecology, Center for Vascular Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20852, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Troisi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008875:Middle Aged; D000072483:Placenta Growth Factor / Q000097:blood*; D017698:Postmenopause / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenesis; Breast cancer risk; PlGF; VEGF; sFlt-1