title: Prognostic effect of circulating adiponectin in a randomized 2 x 2 trial of low-dose tamoxifen and fenretinide in premenopausal women at risk for breast cancer.
abstract: OBJECTIVE
  Adipokines are linked to obesity and insulin sensitivity and have recently been related to breast cancer risk and prognosis. We investigated the associations of plasma leptin and adiponectin with mammographic density and disease status and assessed their prognostic effect on recurrence-free survival in premenopausal women at risk for breast cancer.
  
  
  METHODS
  We measured circulating lipids, insulin-like growth factor 1, glucose, insulin and insulin sensitivity (calculated by homeostasis model assessment [HOMA] index), leptin, adiponectin, and leptin-to-adiponectin ratio in 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), intraepithelial neoplasia (n = 160), or 5-year Gail risk of 1.3% or greater (n = 54) who participated in a 2 × 2 trial of low-dose tamoxifen, fenretinide, both agents, or placebo over a 2-year period.
  
  
  RESULTS
  At baseline, adiponectin levels were directly associated with mammographic density and HDL cholesterol and negatively associated with leptin, leptin-to-adiponectin ratio, body mass index (BMI), and HOMA index. Median adiponectin levels were lower in affected than in unaffected women (P = .006). After a median of 7.2 years and total of 57 breast neoplastic events, there was a 12% reduction in the risk of breast neoplastic events per unit increase of adiponectin (adjusted hazard ratio, 0.88; 95% CI, 0.81 to 0.96; P = .03). There was no interaction between treatment and adiponectin levels.
  
  
  CONCLUSIONS
  Low adiponectin levels are associated with a history of prior intraepithelial neoplasia or pT1mic/pT1a breast cancer and higher risk of second breast neoplastic events in premenopausal women. The associations are independent of BMI, mammographic density, and treatment. Our findings support the role of adiponectin as a potential target for premenopausal breast cancer prevention and treatment.
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Macis
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
authors.forename: Aliana
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.forename: Harriet
authors.initials: H
authors.lastname: Johansson
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
authors.forename: Matteo
authors.initials: M
authors.lastname: Lazzeroni
authors.forename: Davide
authors.initials: D
authors.lastname: Serrano
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: Serena
authors.initials: S
authors.lastname: Mora
authors.forename: Irene
authors.initials: I
authors.lastname: Feroce
authors.forename: Maria
authors.initials: M
authors.lastname: Pizzamiglio
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sandri
authors.forename: Marcella
authors.initials: M
authors.lastname: Gulisano
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
authors.forename: Andrea
authors.initials: A
authors.lastname: Decensi
mesh_terms: D052242:Adiponectin / Q000097:blood*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D017697:Premenopause / Q000097:blood*; D011379:Prognosis; D012307:Risk Factors; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D016588:Anticarcinogenic Agents; D020738:Leptin; D013629:Tamoxifen; D017313:Fenretinide