Analytical Interference of Exemestane With Androstenedione Immunoassays

Background: Exemestane, an aromatase inhibitor commonly used for breast cancer treat- ment, shares structural similarities with sex steroids analyzed in clinical laboratories. We aimed to investigate the influence of exemestane cross-reactivity in the measurement of sex steroids across various immunoassays. Methods: We conducted a multicenter study involving measurements of androstenedione, testosterone, estradiol, progesterone , 17-hydroxyprogesterone in serum samples from women undergoing exemestane therapy (N =15; 25 mg/day). Measurements were per- formed using liquid chromatography-mass spectrometry (LC-MS) , various commercially available chemiluminescence immunoassays, ELISA, and radioimmunoassay. In-vitro cross-reactivity was assessed by adding exemestane and 17-hydroexemestane to serum samples. Results: Patients undergoing exemestane therapy had markedly falsely elevated andro- stenedione results in all immunoassays evaluated (N = 4), which correlated with serum ex- emestane levels. In-vitro experiments confirmed this interference to be caused by cross-re- activity with exemestane. Additionally, one immunoassay yielded falsely elevated estradiol results in 20% of patients. However, in-vitro experiments did not confirm this to be caused by cross-reactivity with exemestane or 17-hydroexemestane. Conclusions: Exemestane cross-reacts with androstenedione immunoassays, causing falsely elevated results in treated patients. This analytical interference may raise unneces- sary concerns, leading to expensive diagnostic workups.