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Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in

Daniel L Hertz1,2, Kelly A Speth3, Kelley M Kidwell4,3

  • 1Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St. Room 3054, Ann Arbor, MI, 48109-1065, USA. dlhertz@med.umich.edu.

Breast Cancer Research and Treatment
|June 24, 2017
PubMed
Abstract

Insights

Plasma drug concentrations of exemestane and letrozole do not correlate with estrogen suppression in breast cancer patients. This finding contrasts with previous research on anastrozole, suggesting different mechanisms of action or patient responses.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Aromatase inhibitors (AIs) like exemestane (EXE), letrozole (LET), and anastrozole are crucial for treating estrogen receptor-positive (ER+) breast cancer by suppressing estrogen biosynthesis.
  • Previous studies indicated a link between anastrozole blood levels and the extent of estrogen suppression.

Purpose of the Study:

  • To investigate if plasma concentrations of exemestane (EXE) or letrozole (LET) are associated with the magnitude of estrogen suppression, measured by plasma estradiol (E2) levels.
  • To compare the relationship between AI concentrations and E2 suppression for EXE and LET, building on prior findings with anastrozole.

Main Methods:

  • The prospective Exemestane and Letrozole Pharmacogenetic (ELPh) Study enrolled 500 post-menopausal women with ER+ breast cancer, randomized to EXE or LET.
  • Plasma E2 concentrations were measured at baseline and 3 months post-treatment; AI concentrations were measured at 1 or 3 months.
  • Statistical analyses compared EXE/LET concentrations with 3-month E2 levels or changes from baseline.

Main Results:

  • Of 400 evaluable patients, 30 (7.6%) had E2 levels above the lower limit of quantification at 3 months.
  • No significant association was found between EXE or LET plasma concentrations and on-treatment E2 levels (p > 0.05).
  • Similarly, AI concentrations did not correlate with the change in E2 levels from baseline to 3 months (p > 0.05).

Conclusions:

  • Steady-state plasma concentrations of exemestane and letrozole do not explain the variability in estradiol suppression in post-menopausal women.
  • This contrasts with prior evidence suggesting a concentration-dependent effect for anastrozole in estrogen suppression.
  • Further research may be needed to understand factors influencing E2 suppression variability in patients treated with EXE or LET.
Keywords:
Aromatase inhibitorBreast cancerEstradiolExemestaneLetrozolePharmacokinetics

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