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

Debora Macis, Sara Gandini, Aliana Guerrieri-Gonzaga, Harriet Johansson, Paolo Magni, Massimiliano Ruscica, Matteo Lazzeroni, Davide Serrano, Massimiliano Cazzaniga, Serena Mora, Irene Feroce, Maria Pizzamiglio, Maria Teresa Sandri, Marcella Gulisano, Bernardo Bonanni, Andrea DeCensi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Patients and 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 x 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number2
DOIs
Publication statusPublished - Jan 10 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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