Originally published as JCO Early Release 10.1200/JCO.2005.07.097 on June 27 2005

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Effects of Exemestane Administered for 2 Years Versus Placebo on Bone Mineral Density, Bone Biomarkers, and Plasma Lipids in Patients With Surgically Resected Early Breast Cancer

From the Section of Oncology, Department of Medicine, Haukeland University Hospital; Laboratory for Clinical Biochemistry, Haukeland University Hospital; Center for Clinical Trials, Bergen; Department of Surgery, Rogaland Central Hospital, Stavanger; Department of Oncology, The Norwegian Radiumhospital; Department of Surgery, Ullevaal University Hospital, Oslo; Department of Oncology, University Hospital of North Norway, Tromsø; Department of Surgery, St Olavs Hospital, Trondheim, Norway; and Pharmacia Italia SpA, Pfizer Group, Clinical Development, Milan, Italy

Address reprint requests to Per Eystein Lønning, Section of Oncology, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway; e-mail: per.lonning{at}helse-bergen.no

PURPOSE: To evaluate potential detrimental effects of exemestane on bone and lipid metabolism.

PATIENTS AND METHODS: Postmenopausal women with early breast cancer were randomly assigned to exemestane 25 mg daily or placebo for 2 years in a double-blind setting. Primary objective was to evaluate the effect of exemestane on bone mineral density. Secondary objectives were effects on bone biomarkers, plasma lipids, coagulation factors, and homocysteine. Planned size was 128 patients.

RESULTS: One hundred forty-seven patients were enrolled. All patients completed their 24-month visit except for those discontinuing treatment at an earlier stage. The mean annual rate of bone mineral density loss was 2.17% v 1.84% in the lumbar spine (P = .568) and 2.72% v 1.48% in the femoral neck (P = .024) in the exemestane and placebo arm, respectively. The mean change in T-score after 2 years was –0.21 for exemestane and –0.11 on placebo in the hip, and –0.30 and –0.21, respectively, in the lumbar spine. Exemestane significantly increased serum level and urinary excretion of bone resorption, but also bone formation markers. Except for a modest reduction in high-density lipoprotein cholesterol (P < .001) and apolipoprotein A1 (P = .004), exemestane had no major effect on lipid profile, homocysteine levels, or coagulation parameters.

CONCLUSION: Exemestane modestly enhanced bone loss from the femoral neck without significant influence on lumbar bone loss. Except for a 6% to 9% drop in plasma high-density lipoprotein cholesterol, no major effects on serum lipids, coagulation factors, or homocysteine were recorded. Bone mineral density should be assessed according to the US Preventive Services Task Force guidelines.

Supported by Pfizer Inc; P.E.L. and J.G. both received speakers honorarium from Pfizer Inc as well as AstraZeneca and Novartis (the major companies involved in development of aromatase inhibitors), and research support from the same companies.

Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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