Does obesity interfere with anastrozole treatment? Positive association between body mass index and anastrozole plasma levels.
BACKGROUND
The efficacy of adjuvant endocrine treatment with aromatase inhibitors (AIs), inhibiting the conversion of androgens to estrogen in adipose tissue, might depend on the overall volume of adipose tissue. However, little evidence is available regarding the pharmacokinetic behavior of AIs in women with obesity. The aim of this study was to investigate the interaction between body mass index (BMI) and anastrozole treatment as well as estrogenic activity.


METHODS
A total of 216 postmenopausal patients with early-stage breast cancer who were receiving AI treatment with anastrozole constituted the final sample included in the analysis. During a regular 3-month after-care check-up, sociodemographic and clinical data and BMI were assessed. Blood samples were collected during routine blood testing. Measurement of AI plasma levels was performed by liquid chromatography-tandem mass spectrometry. Follicle stimulating hormone (FSH) and estradiol were measured within the routine blood examination.


RESULTS
A median anastrozole plasma concentration of 34.7 ng/mL (mean, 37.4), with a large interindividual variability, was observed (SD, 15.1; range, 5.4-86.5). After age adjustment, it was found that anastrozole plasma concentrations significantly increased with BMI (r = 0.241; P = .001). Anastrozole serum concentrations in women with obesity (BMI ≥ 30) exceeded those of women with normal weight (BMI ≤ 25) by 25%. Women with excess weight had lower mean FSH levels, indicating higher estrogenic activity, compared with women with normal weight.


CONCLUSIONS
This study indicates that BMI is a vital factor in anastrozole metabolism, as measured by anastrozole plasma concentration and FSH levels. Further research is mandatory to clarify results on the association of obesity and AI treatment efficacy to allow adapting AI treatment accordingly.
Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Michael.hubalek@i-med.ac.at.
Michael
M
Hubalek
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Anne
A
Oberguggenberger
Institute of Legal Medicine and Core Facility Metabolomics, Innsbruck Medical University, Innsbruck, Austria.
Beate
B
Beer
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Verena
V
Meraner
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Monika
M
Sztankay
Institute of Legal Medicine and Core Facility Metabolomics, Innsbruck Medical University, Innsbruck, Austria.
Herbert
H
Oberacher
Institute of Legal Medicine and Core Facility Metabolomics, Innsbruck Medical University, Innsbruck, Austria.
Birthe
B
Schubert
Department of Gynecological Endocrinology and Reproductive Medicine, Innsbruck Medical University, Innsbruck, Austria.
Ludwig
L
Wildt
Department of Gynecological Endocrinology and Reproductive Medicine, Innsbruck Medical University, Innsbruck, Austria.
Beata
B
Seeber
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Johannes
J
Giesinger
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Georg
G
Kemmler
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Bernhard
B
Holzner
Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.
Barbara
B
Sperner-Unterweger
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000728:Androgens / Q000097:blood; D047072:Aromatase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009765:Obesity / Q000503:physiopathology*; D017698:Postmenopause; D011379:Prognosis; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000728:Androgens; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D004958:Estradiol; D005640:Follicle Stimulating Hormone
Anastrozole treatment efficacy, Aromatase inhibitor; Aromatase inhibitor; Association of BMI and AI plasma concentrations; BMI; Breast cancer; Levels