Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors

Valerie J. Wiebe, C. Kent Osborne, William L. McGuire, Michael W. DeGregorio

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Purpose: We hove shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. Patients and Methods: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. Results: We identified the presence of metabolite E, a known estrogenic metabolite of tamexifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. Conclusion: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted.

Original languageEnglish (US)
Pages (from-to)990-994
Number of pages5
JournalJournal of Clinical Oncology
Volume10
Issue number6
StatePublished - 1992
Externally publishedYes

Fingerprint

Tamoxifen
Breast Neoplasms
Nude Mice
Mass Spectrometry
High Pressure Liquid Chromatography
Neoplasms
Growth Hormone
Theoretical Models
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wiebe, V. J., Osborne, C. K., McGuire, W. L., & DeGregorio, M. W. (1992). Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. Journal of Clinical Oncology, 10(6), 990-994.

Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. / Wiebe, Valerie J.; Osborne, C. Kent; McGuire, William L.; DeGregorio, Michael W.

In: Journal of Clinical Oncology, Vol. 10, No. 6, 1992, p. 990-994.

Research output: Contribution to journalArticle

Wiebe, VJ, Osborne, CK, McGuire, WL & DeGregorio, MW 1992, 'Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors', Journal of Clinical Oncology, vol. 10, no. 6, pp. 990-994.
Wiebe, Valerie J. ; Osborne, C. Kent ; McGuire, William L. ; DeGregorio, Michael W. / Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. In: Journal of Clinical Oncology. 1992 ; Vol. 10, No. 6. pp. 990-994.
@article{242083f1461241219d70f9b44a759240,
title = "Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors",
abstract = "Purpose: We hove shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. Patients and Methods: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. Results: We identified the presence of metabolite E, a known estrogenic metabolite of tamexifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. Conclusion: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted.",
author = "Wiebe, {Valerie J.} and Osborne, {C. Kent} and McGuire, {William L.} and DeGregorio, {Michael W.}",
year = "1992",
language = "English (US)",
volume = "10",
pages = "990--994",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors

AU - Wiebe, Valerie J.

AU - Osborne, C. Kent

AU - McGuire, William L.

AU - DeGregorio, Michael W.

PY - 1992

Y1 - 1992

N2 - Purpose: We hove shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. Patients and Methods: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. Results: We identified the presence of metabolite E, a known estrogenic metabolite of tamexifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. Conclusion: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted.

AB - Purpose: We hove shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. Patients and Methods: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. Results: We identified the presence of metabolite E, a known estrogenic metabolite of tamexifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. Conclusion: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted.

UR - http://www.scopus.com/inward/record.url?scp=0026632964&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026632964&partnerID=8YFLogxK

M3 - Article

C2 - 1588380

AN - SCOPUS:0026632964

VL - 10

SP - 990

EP - 994

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 6

ER -