Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole

James N. Ingle, Krishna R Kalari, Aman U. Buzdar, Mark E. Robson, Matthew Philip Goetz, Zeruesenay Desta, Poulami Barman, Tanda T. Dudenkov, Donald W Northfelt, Edith A. Perez, David A. Flockhart, Clark V. Williard, Liewei M Wang, Richard M Weinshilboum

Research output: Contribution to journalArticle

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Abstract

Purpose: We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites. Experimental: Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4. weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays. Results: 649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79% and 70%, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0. pg/mL, 1.562-183.2. pg/mL, respectively). Considering E2, 8.9% had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug. Conclusions: We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1. mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.

Original languageEnglish (US)
JournalSteroids
DOIs
StateAccepted/In press - May 1 2014

Fingerprint

Estrogens
Breast Neoplasms
Estrone
Metabolites
Hormones
Assays
anastrozole
Plasmas
Blood
Androstenedione
Tandem Mass Spectrometry
Gas chromatography
Gas Chromatography
Ionization
Mass spectrometry
Testosterone
Estradiol

Keywords

  • Anastrozole
  • Androstenedione
  • Estradiol
  • Estrone
  • Estrone conjugates
  • Testosterone

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole. / Ingle, James N.; Kalari, Krishna R; Buzdar, Aman U.; Robson, Mark E.; Goetz, Matthew Philip; Desta, Zeruesenay; Barman, Poulami; Dudenkov, Tanda T.; Northfelt, Donald W; Perez, Edith A.; Flockhart, David A.; Williard, Clark V.; Wang, Liewei M; Weinshilboum, Richard M.

In: Steroids, 01.05.2014.

Research output: Contribution to journalArticle

Ingle, James N. ; Kalari, Krishna R ; Buzdar, Aman U. ; Robson, Mark E. ; Goetz, Matthew Philip ; Desta, Zeruesenay ; Barman, Poulami ; Dudenkov, Tanda T. ; Northfelt, Donald W ; Perez, Edith A. ; Flockhart, David A. ; Williard, Clark V. ; Wang, Liewei M ; Weinshilboum, Richard M. / Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole. In: Steroids. 2014.
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abstract = "Purpose: We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites. Experimental: Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4. weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays. Results: 649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79{\%} and 70{\%}, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0. pg/mL, 1.562-183.2. pg/mL, respectively). Considering E2, 8.9{\%} had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug. Conclusions: We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1. mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.",
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author = "Ingle, {James N.} and Kalari, {Krishna R} and Buzdar, {Aman U.} and Robson, {Mark E.} and Goetz, {Matthew Philip} and Zeruesenay Desta and Poulami Barman and Dudenkov, {Tanda T.} and Northfelt, {Donald W} and Perez, {Edith A.} and Flockhart, {David A.} and Williard, {Clark V.} and Wang, {Liewei M} and Weinshilboum, {Richard M}",
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AU - Ingle, James N.

AU - Kalari, Krishna R

AU - Buzdar, Aman U.

AU - Robson, Mark E.

AU - Goetz, Matthew Philip

AU - Desta, Zeruesenay

AU - Barman, Poulami

AU - Dudenkov, Tanda T.

AU - Northfelt, Donald W

AU - Perez, Edith A.

AU - Flockhart, David A.

AU - Williard, Clark V.

AU - Wang, Liewei M

AU - Weinshilboum, Richard M

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Purpose: We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites. Experimental: Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4. weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays. Results: 649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79% and 70%, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0. pg/mL, 1.562-183.2. pg/mL, respectively). Considering E2, 8.9% had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug. Conclusions: We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1. mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.

AB - Purpose: We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites. Experimental: Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4. weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays. Results: 649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79% and 70%, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0. pg/mL, 1.562-183.2. pg/mL, respectively). Considering E2, 8.9% had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug. Conclusions: We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1. mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.

KW - Anastrozole

KW - Androstenedione

KW - Estradiol

KW - Estrone

KW - Estrone conjugates

KW - Testosterone

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