scholarly journals An Ultrasensitive Routine LC-MS/MS Method for Estradiol and Estrone in the Clinically Relevant Sub-Picomolar Range

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Bjørn-Erik Bertelsen ◽  
Ralf Kellmann ◽  
Kristin Viste ◽  
Anne Turid Bjørnevik ◽  
Hans Petter Eikesdal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Cancer Patients ◽  
Aromatase Inhibitors ◽  
Internal Standard ◽  
Postmenopausal Breast Cancer ◽  
Reference Ranges ◽  
Breast Cancer Patients ◽  
Endocrine Society ◽  
Lh Releasing Hormone

Abstract Background Current analytical routine methods lack the sensitivity to monitor plasma estrogen levels in breast cancer patients treated with aromatase inhibitors. Such monitoring is warranted for premenopausal patients treated with an aromatase inhibitor and an LH-releasing hormone analogue in particular. Therefore, we aimed to develop a routine tandem mass spectroscopy combined with liquid chromatography (LC-MS/MS) method for estradiol (E2) and estrone (E1) for use in the sub-picomolar range. Method Calibrators, quality controls (QC), or serum samples were spiked with isotope-labeled internal standard and purified by liquid-liquid extraction. The reconstituted extracts were analyzed by LC-MS/MS in negative electrospray ionization mode. QCs at 6 levels made from pooled patient sera were used to validate the accuracy, sensitivity, and precision of the method. Results We achieved limits of quantification of 0.6 pmol/L (0.16 pg/mL) for E2 and 0.3 pmol/L (0.07 pg/mL) for E1. The coefficient of variation was below 9.0% at all QC levels for E2 (range, 1.7-153 pmol/L), and below 7.8% for E1 (range, 1.7-143 pmol/L). The method is traceable to the E2 reference standard BCR576. Reference ranges for E2 and E1 in healthy, postmenopausal women were obtained, for E2: 3.8 to 36 pmol/L, for E1: 22 to 122 pmol/L. We measured and confirmed ultra-low E2 and E1 concentrations in sera from patients on the aromatase inhibitors letrozole or exemestane. Conclusion This ultrasensitive LC-MS/MS method is suitable for routine assessment of serum E1 and E2 levels in breast cancer patients during estrogen suppression therapy. The method satisfies all requirements for measurement of E2 in the clinical setting as stated by the Endocrine Society in 2013. Precis We report an ultrasensitive LCMS/MS routine assay that measures pretreatment and suppressed levels of estradiol/estrone during aromatase inhibitor treatment of postmenopausal breast cancer patients.

scholarly journals Assessment of cardiotoxicity in hormone positive postmenopausal breast cancer patients receiving aromatase inhibitors

2019 ◽  
Vol 9 (1) ◽  
pp. 11
Author(s):  
Reham M. Faheim ◽  
Eman A. El-Shaarawy ◽  
Dina A. Salem ◽  
Rehab G. Shaaban
Keyword(s):  
Breast Cancer ◽  
Blood Pressure ◽  
Lipid Profile ◽  
Cancer Patients ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Postmenopausal Breast Cancer ◽  
P Value ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive

Background: Aromatase inhibitors (AIs) represent an effective endocrine treatment for hormone receptor-positive postmenopausal breast cancer patients with early stage or metastatic disease.Objective: Assessment of Cardiotoxicity in Hormone positive Postmenopausal Breast Cancer Patients receiving AIs (upfront orswitch therapy).Methods: This cross sectional study included 123 postmenopausal breast cancer patients presented to the Clinical Oncology Department, Ain Shams University (Cairo, Egypt) in the interval from August 2016 to June 2017 with hormone receptor positive receiving Aromatase Inhibitors, To assess cardiotoxicity in these patients, they were subjected to blood pressure and lipid profile measurement, electrocardiography (ECG), and electrocardiography (ECHO) and classified into patients had Nolvadex then A.I (arm 1) and others had upfront A.I (arm 2).Results: The age of patients ranged from 41 years to 85 years with mean age of 61 years. Seventy one patients (57.7%) showed cardiotoxicity as assessed by ECHO. They showed significant correlation with rising age above 62 years, IHD, history of HTN and DM (p value: .001, .001, .017 and 0.035 respectively). However, correlation between cardiotoxity and blood pressure changes, lipid profile changes and ECG findings and ECHO changes in switch therapy and upfront A.I were not statistically significant (p value = .275, .116, .081 and .761 respectively).Conclusion: Assessment of cardiotoxicity in hormone positive postmenopausal breast cancer patients receiving Aromatase Inhibitors showed evidence of cardiotoxicity in half the patients (57.7%) as detected by ECHO only. They showed statistically non significant correlations either recievied switch therapy or upfront A.I.

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