B-117 Analytical evaluation of a new high-sensitivity Estradiol test: a study on a cohort of cancer patients

Abstract

Estradiol (E2) is a key estrogenic steroid hormone involved in the regulation of female reproductive physiology. In several clinical settings, such as in postmenopausal women or in patients with hormone-sensitive breast cancer receiving endocrine therapy, circulating E2 concentrations reach extremely low levels. In these settings, the analytical sensitivity of laboratory assays becomes a critical determinant of clinical utility. Conventional automated immunoassays, widely used in routine practice, generally exhibit functional sensitivity limits around 15–20 pg/mL, which may be insufficient for accurate quantification in estrogen-suppressed conditions. Highly sensitive methods capable of reliably quantifying E2 concentrations down to a few pg/mL are therefore essential for both clinical assessment and therapeutic monitoring. This study aims to evaluate the analytical performance of a new high-intensity sandwich chemiluminescence immunoassay with enhanced sensitivity, focusing on its ability to detect low E2 concentrations (3 pg/mL), and to compare its performance with liquid chromatography–tandem mass spectrometry (LC-MS/MS), the current reference method. A total of 313 female patients were enrolled, divided into: 59 healthy fertile women (18-44 years old, y.o.), 66 pre-adolescent girls (9-14 y.o.), 60 children (3-8 y.o.), 56 menopausal women (45-65 y.o.), and 64 breast cancer patients undergone to E2 suppression therapy. Serum E2 levels were measured using LC-MS/MS (Chromsystems) and three automated immunoassays: CL-1200i (Mindray), Atellica CI Analyzer (Siemens), and cobas e411 (Roche). Method comparison by Passing-Bablok analysis and Bland-Altman was performed to assess agreement and analytical accuracy, particularly at low E2 concentrations. Precision and linearity were assessed. The Mindray assay demonstrated strong correlation and concordance with LC-MS/MS, particularly in the low-concentration range (E2 values < 30 pg/mL). Spearman's rank correlation coefficient (r) was 0.915 between LC-MS/MS and Mindray, 0.809 between LC-MS/MS and Siemens, and 0.587 between LC-MS/MS and Roche (p < 0.0001). Moreover, 12.5% (8/64) of breast cancer patients undergoing estradiol suppression therapy exhibited E2 concentrations in the 4–15 pg/mL range, which would likely be undetected by standard immunoassays. Precision was evaluated through 5 replicates of quality control samples analyzed for 5 consecutive days. The results showed a Coefficient of Variation (%CV) of 2%. The findings of this study indicate that the Mindray chemiluminescent immunoassay achieves analytical performance at low estradiol concentrations that is consistent with LC-MS/MS. Its capacity to reliably quantify E2 concentrations down to 3 pg/mL supports its potential application in therapeutic drug monitoring in estrogen-suppressed patients, in whom accurate low-level estradiol measurement is clinically critical for the precise evaluation of treatment efficacy and adherence in hormone-dependent conditions.