Exemestane Cross-Reacts with All Androstenedione Immunoassays, Causing Falsely Elevated Results
In a multicenter study of 15 women on exemestane therapy, all four androstenedione immunoassays produced markedly falsely elevated results that correlated with serum exemestane concentrations, confirmed by in-vitro cross-reactivity experiments. LC-MS was unaffected. One estradiol immunoassay also yielded false elevations in 20% of patients, though the mechanism was less clear. The findings highlight that exemestane interference can trigger unnecessary diagnostic workups and underscore the need for MS-based methods or at minimum clinician awareness when interpreting steroid results in breast cancer patients.
The original study
Analytical Interference of Exemestane With Androstenedione Immunoassays.
- Authors
- Giralt M, Ferrer R, Díaz-Troyano N, Vega B, Luque-Ramírez M, Martínez S, et al.
- Journal
- Annals of laboratory medicine
- Type
- Journal Article, Multicenter Study
- PMID
- 40114653
Original abstract
BACKGROUND: Exemestane, an aromatase inhibitor commonly used for breast cancer treatment, 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, and 17-hydroxyprogesterone in serum samples from women undergoing exemestane therapy (N=15; 25 mg/day). Measurements were performed using liquid chromatography-mass spectrometry (LC-MS) and 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 androstenedione results in all immunoassays evaluated (N=4), which correlated with serum exemestane levels. In-vitro experiments confirmed this interference to be caused by cross-reactivity 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 unnecessary concerns, leading to expensive diagnostic workups.