Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer

Jason D. Robarge, Zeruesenay Desta, Anne T. Nguyen, Lang Li, Daniel Hertz, James M. Rae, Daniel F. Hayes, Anna Maria Storniolo, Vered Stearns, David A. Flockhart, Todd Skaar, N. L. Henry

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. Methods: In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. Results: The ranges of baseline estrogen concentrations were <LLOQ–361 pg/mL for E2, <LLOQ–190 pg/mL for E1, and 8.3–4060 pg/mL for E1S. For E2, the frequency of suppression below the LLOQ was not statistically significantly different between AIs (exemestane: 89.0%, letrozole: 86.9%, p = 0.51). However, patients on letrozole were more likely to achieve suppression below the LLOQ of both E1 (exemestane: 80.1%, letrozole: 90.1%, p = 0.005) and E1S (exemestane: 17.4%, letrozole: 54.9%, p = 4.34e−15). After 3 months of AI therapy, the ranges of estrogen concentrations were <LLOQ–63.8 pg/mL, <LLOQ–36.7 pg/mL, and <LLOQ–1090 pg/mL for E2, E1, and E1S, respectively. During treatment, 16 patients had an increased concentration compared to the baseline concentration of at least one estrogen. Conclusions: Letrozole had greater suppression of plasma E1 and E1S than exemestane, though the response was highly variable among patients. Additional research is required to examine the clinical relevance of differential estrogen suppression.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Dec 9 2016

Fingerprint

exemestane
letrozole
Estrogens
Aromatase Inhibitors
Breast Neoplasms
Therapeutics
Estrone
Individuality
Multicenter Studies

Keywords

  • Breast cancer
  • Estradiol
  • Estrone
  • Estrone sulfate
  • Exemestane
  • Letrozole

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer. / Robarge, Jason D.; Desta, Zeruesenay; Nguyen, Anne T.; Li, Lang; Hertz, Daniel; Rae, James M.; Hayes, Daniel F.; Storniolo, Anna Maria; Stearns, Vered; Flockhart, David A.; Skaar, Todd; Henry, N. L.

In: Breast Cancer Research and Treatment, 09.12.2016, p. 1-9.

Research output: Contribution to journalArticle

Robarge, Jason D. ; Desta, Zeruesenay ; Nguyen, Anne T. ; Li, Lang ; Hertz, Daniel ; Rae, James M. ; Hayes, Daniel F. ; Storniolo, Anna Maria ; Stearns, Vered ; Flockhart, David A. ; Skaar, Todd ; Henry, N. L. / Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer. In: Breast Cancer Research and Treatment. 2016 ; pp. 1-9.
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AU - Robarge, Jason D.

AU - Desta, Zeruesenay

AU - Nguyen, Anne T.

AU - Li, Lang

AU - Hertz, Daniel

AU - Rae, James M.

AU - Hayes, Daniel F.

AU - Storniolo, Anna Maria

AU - Stearns, Vered

AU - Flockhart, David A.

AU - Skaar, Todd

AU - Henry, N. L.

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N2 - Purpose: Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. Methods: In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. Results: The ranges of baseline estrogen concentrations were <LLOQ–361 pg/mL for E2, <LLOQ–190 pg/mL for E1, and 8.3–4060 pg/mL for E1S. For E2, the frequency of suppression below the LLOQ was not statistically significantly different between AIs (exemestane: 89.0%, letrozole: 86.9%, p = 0.51). However, patients on letrozole were more likely to achieve suppression below the LLOQ of both E1 (exemestane: 80.1%, letrozole: 90.1%, p = 0.005) and E1S (exemestane: 17.4%, letrozole: 54.9%, p = 4.34e−15). After 3 months of AI therapy, the ranges of estrogen concentrations were <LLOQ–63.8 pg/mL, <LLOQ–36.7 pg/mL, and <LLOQ–1090 pg/mL for E2, E1, and E1S, respectively. During treatment, 16 patients had an increased concentration compared to the baseline concentration of at least one estrogen. Conclusions: Letrozole had greater suppression of plasma E1 and E1S than exemestane, though the response was highly variable among patients. Additional research is required to examine the clinical relevance of differential estrogen suppression.

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