Exemestane significantly reduced invasive breast cancer in postmenopausal women with an elevated risk of developing the disease, but the aromatase inhibitor also had the undesirable effect of lowering high-density lipoprotein (HDL) cholesterol levels.

A phase II multicenter study of 31 women (mean age 58.5 years) at increased risk for breast cancer evaluated the safety and efficacy of exemestane over 2 years of therapy. More than half the women (19) were on lipid-lowering medications prior to starting the trial—14 were taking statins and five were taking fish-oil supplements. Statin therapy was initiated in one woman approximately 10 months after the start of the trial.

In adjusted analyses, HDL levels decreased for women both off and on lipid-lowering medication from baseline at all subsequent assessment points—3, 12, and 24 months—falling by 8.0 mg/dL, 8.5 mg/dL, and 9.9 mg/dL, respectively from baseline. Total cholesterol also significantly decreased from baseline at 3 months (falling 13.6 mg/dL), but the decline was no longer significant at 12 or 24 months.

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The rest of the lipid panel did not change significantly during follow-up. At 35 months follow-up, no increased risk of cardiovascular events was observed.

Although other studies have also shown exemestane to significantly reduce HDL and total cholesterol levels while leaving the rest of the lipid panel unchanged, those studies excluded patients on lipid-lowering therapy, pointed out  investigator Margaret Gatti-Mays, MD, of Georgetown University Medical Center in Washington, DC, and colleagues. The researchers, who presented their findings at the CTRC-AACR San Antonio Breast Cancer Symposium, held December 6-10, 2011, in San Antonio, Texas, noted that more studies are needed to evaluate the impact of exemestane on cholesterol and cardiovascular health in this high-risk but otherwise healthy population.