1517 Background: When used in the adjuvant setting, aromatase inhibitors (AIs) reduce the incidence of contralateral breast cancer and are therefore under investigation for primary breast cancer prevention. Statins hold promise for chemoprevention based on preclinical and epidemiological data. Adding statin to AI has the potential to enhance breast cancer prevention and to protect women from AI-related side effects. Prior to initiating a chemoprevention trial of combination therapy, we evaluated the potential for pharmacokinetic drug-drug interaction between anastrozole and simvastatin in postmenopausal women taking adjuvant anastrozole to ensure that the combination will not influence anastrozole concentration or affect its ability to reduce estrogen. Methods: Postmenopausal women with hormone receptor-positive, stage 0-III breast cancer who had been on adjuvant anastrozole (1 mg/day) for at least 30 days were prescribed 14 days of simvastatin (40 mg/day). We collected serum at baseline (anastrozole alone) and after 14 days of simvastatin initiation (combination therapy). Anastrozole and hydroxyanastrozole, its hydroxylated metabolite, concentrations were determined using liquid chromatography-tandem mass spectrometry assay. Estrogen concentrations will be determined using radio-immunoassay. Significant change in anastrozole was predetermined to be greater than a 30% decrease in concentrations. Percent changes from baseline in anastrozole and hydroxyanastrozole were evaluated using Wilcoxon signed-rank tests. Results: From December 2006 to September 2008, 11 women (10 Caucasian, 1 Black, all reported non-Hispanic with a mean age of 60 yrs [range 51–69]) were enrolled in the study. Of these women, nine had evaluable anastrozole concentrations. After 14 days of simvastatin, there were nonsignificant changes in anastrozole (median percentage difference = 10.1% [-13.5%, 38.4%], p = 0.36) and hydroxyanastrozole (median percentage difference = -3.0% [-19.1%, 11.2%], p = 0.65). Estrogen data will be available for presentation. Conclusions: Simvastatin is unlikely to alter the pharmacokinetics of anastrozole in a clinically meaningful way. Combination studies to assess chemopreventive properties of the combination are planned. [Table: see text]
Exemestane for Breast-Cancer Prevention in Postmenopausal Women