Abstract
Background: The assessment of breast cancer risk is a key step for an effective preventive treatment. Besides the established risk assessment models, independent predictive factors like circulating biomarkers may also be important to better select high risk subjects and to determine efficacy of chemopreventive treatment.
Adiponectin is a peptide hormone secreted from the adipose tissue with anti-inflammatory, anti-atherogenic and anti-diabetic properties. Epidemiological studies have shown that plasma adiponectin level is inversely related to breast cancer risk.
In the present study, we measured plasma adiponectin levels in premenopausal women participating in a phase II trial of low-dose tamoxifen and fenretinide for breast cancer prevention.
Methods: Premenopausal women (n = 235) were randomly assigned in a double-blind 2x2 trial to receive tamoxifen 5 mg/d, fenretinide, a vitamin A derivative, 200 mg/d, both agents, or placebo for 2 years. A total of 181 premenopausal women with ductal intraepithelial neoplasia (DIN) and 54 unaffected women at higher risk according to the Gail model were enrolled.
Mammographic percent density was centrally measured using the computer-assisted method described by Boyd. Plasma adiponectin was measured by use of a commercial enzyme-linked immunosorbent assay kit.
Preliminary results: According to disease status (DIN vs Gail) at baseline, median plasma adiponectin levels were lower in women with a DIN (10 ug/ml; interquartile (IQ) range: 7.1-14) compared to unaffected women with a Gail risk (12 ug/ml; IQ range: 8.7-14.7) (p=0.05).
Importantly, after a median follow-up of 5.5 years, plasma adiponectin levels were lower in women who had a breast cancer event (7.7 ug/mL; IQ range: 6.46-12.78) compared to women without event (11.02 ug/mL; IQ range: 7.8-14.4) (p=0.015). This difference is also maintained after adjusting for BMI and treatment allocation (p=0.011).
Considering the distribution of adiponectin levels at baseline, we observed a 9% reduction in the hazard ratio of breast cancer events by each unit increase of adiponectin levels (95%CI: 0.83-0.96; p=0.02, cox model adjusted for BMI, treatment allocation, mammographic density and disease status at baseline).
Conclusion: We found that subjects with lower plasma adiponectin levels had a significantly higher risk of breast cancer event. The association appeared independent of known risk factors such as BMI and mammographic breast density. Further studies to better understand and confirm the role of adiponectin as independent predictive risk factor are warranted.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A61.
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