Personalized medicine in breast cancer

Tamoxifen, endoxifen, and CYP2D6 in clinical practice

Kathryn J Ruddy, Stephen D. Desantis, Rebecca S. Gelman, Alan H B Wu, Rinaa S. Punglia, Erica L. Mayer, Sara M. Tolaney, Eric P. Winer, Ann H. Partridge, Harold J. Burstein

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Abstract: Tamoxifen is metabolized into endoxifen, a potent antagonist of the estrogen receptor, in part through cytochrome p450 (CYP) 2D6. Genotypic variation in CYP2D6 affects endoxifen levels, and some have argued that patients who do not efficiently metabolize tamoxifen might wish to consider alternative hormonal treatments. This study evaluated an algorithm in which endoxifen levels and CYP2D6 genotypes were used to make hormonal therapy recommendations for patients on adjuvant tamoxifen for breast cancer. Patients with stage I-III breast cancer who had been taking adjuvant tamoxifen for 8-56 weeks were eligible. At enrollment, baseline whole blood and serum were sent for genotyping by Amplichip and endoxifen measurement, respectively, and endoxifen levels were also measured 3 weeks later. Results were returned to oncologists along with an algorithm-generated treatment recommendation. The algorithm recommended that participants with poor metabolizer genotype and/or baseline endoxifen level <6 ng/mL consider alternative endocrine therapy. A medical record review evaluated actual treatment decisions. Of 99 patients on study, 18 (18 %) had findings that triggered algorithm-based recommendations to consider a change in endocrine therapy due to endoxifen <6 ng/mL (all 18 patients) and/or poor metabolizer CYP2D6 genotype (2 of the 18). Endoxifen levels were ≥6 ng/mL in four of them 3 weeks later. Seven (39 % of 18) switched to a different treatment (one based on toxicity, not the algorithm). Hot flash burden was not found to be significantly associated with endoxifen <6 ng/mL or genotype. Prospective testing of tamoxifen metabolism as gauged by CYP2D6 genotype and serum endoxifen levels is feasible. Future studies of tamoxifen metabolism and efficacy should consider including measurement of serial endoxifen levels. Although clinical evidence at present is insufficient to warrant routine CYP2D6 or endoxifen testing, some clinicians and patients did utilize this predefined algorithm to inform clinical decisions regarding optimal adjuvant endocrine therapy.

Original languageEnglish (US)
Pages (from-to)421-427
Number of pages7
JournalBreast Cancer Research and Treatment
Volume141
Issue number3
DOIs
StatePublished - Oct 2013
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP2D6
Precision Medicine
Tamoxifen
Breast Neoplasms
Genotype
Therapeutics
4-hydroxy-N-desmethyltamoxifen
Hot Flashes
Complementary Therapies
Serum
Medical Records

Keywords

  • Antineoplastic agents/hormonal
  • Breast neoplasms
  • Genotype
  • Tamoxifen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ruddy, K. J., Desantis, S. D., Gelman, R. S., Wu, A. H. B., Punglia, R. S., Mayer, E. L., ... Burstein, H. J. (2013). Personalized medicine in breast cancer: Tamoxifen, endoxifen, and CYP2D6 in clinical practice. Breast Cancer Research and Treatment, 141(3), 421-427. https://doi.org/10.1007/s10549-013-2700-1

Personalized medicine in breast cancer : Tamoxifen, endoxifen, and CYP2D6 in clinical practice. / Ruddy, Kathryn J; Desantis, Stephen D.; Gelman, Rebecca S.; Wu, Alan H B; Punglia, Rinaa S.; Mayer, Erica L.; Tolaney, Sara M.; Winer, Eric P.; Partridge, Ann H.; Burstein, Harold J.

In: Breast Cancer Research and Treatment, Vol. 141, No. 3, 10.2013, p. 421-427.

Research output: Contribution to journalArticle

Ruddy, KJ, Desantis, SD, Gelman, RS, Wu, AHB, Punglia, RS, Mayer, EL, Tolaney, SM, Winer, EP, Partridge, AH & Burstein, HJ 2013, 'Personalized medicine in breast cancer: Tamoxifen, endoxifen, and CYP2D6 in clinical practice', Breast Cancer Research and Treatment, vol. 141, no. 3, pp. 421-427. https://doi.org/10.1007/s10549-013-2700-1
Ruddy, Kathryn J ; Desantis, Stephen D. ; Gelman, Rebecca S. ; Wu, Alan H B ; Punglia, Rinaa S. ; Mayer, Erica L. ; Tolaney, Sara M. ; Winer, Eric P. ; Partridge, Ann H. ; Burstein, Harold J. / Personalized medicine in breast cancer : Tamoxifen, endoxifen, and CYP2D6 in clinical practice. In: Breast Cancer Research and Treatment. 2013 ; Vol. 141, No. 3. pp. 421-427.
@article{2069d0038b50440c8a121bb36233c8f9,
title = "Personalized medicine in breast cancer: Tamoxifen, endoxifen, and CYP2D6 in clinical practice",
abstract = "Abstract: Tamoxifen is metabolized into endoxifen, a potent antagonist of the estrogen receptor, in part through cytochrome p450 (CYP) 2D6. Genotypic variation in CYP2D6 affects endoxifen levels, and some have argued that patients who do not efficiently metabolize tamoxifen might wish to consider alternative hormonal treatments. This study evaluated an algorithm in which endoxifen levels and CYP2D6 genotypes were used to make hormonal therapy recommendations for patients on adjuvant tamoxifen for breast cancer. Patients with stage I-III breast cancer who had been taking adjuvant tamoxifen for 8-56 weeks were eligible. At enrollment, baseline whole blood and serum were sent for genotyping by Amplichip and endoxifen measurement, respectively, and endoxifen levels were also measured 3 weeks later. Results were returned to oncologists along with an algorithm-generated treatment recommendation. The algorithm recommended that participants with poor metabolizer genotype and/or baseline endoxifen level <6 ng/mL consider alternative endocrine therapy. A medical record review evaluated actual treatment decisions. Of 99 patients on study, 18 (18 {\%}) had findings that triggered algorithm-based recommendations to consider a change in endocrine therapy due to endoxifen <6 ng/mL (all 18 patients) and/or poor metabolizer CYP2D6 genotype (2 of the 18). Endoxifen levels were ≥6 ng/mL in four of them 3 weeks later. Seven (39 {\%} of 18) switched to a different treatment (one based on toxicity, not the algorithm). Hot flash burden was not found to be significantly associated with endoxifen <6 ng/mL or genotype. Prospective testing of tamoxifen metabolism as gauged by CYP2D6 genotype and serum endoxifen levels is feasible. Future studies of tamoxifen metabolism and efficacy should consider including measurement of serial endoxifen levels. Although clinical evidence at present is insufficient to warrant routine CYP2D6 or endoxifen testing, some clinicians and patients did utilize this predefined algorithm to inform clinical decisions regarding optimal adjuvant endocrine therapy.",
keywords = "Antineoplastic agents/hormonal, Breast neoplasms, Genotype, Tamoxifen",
author = "Ruddy, {Kathryn J} and Desantis, {Stephen D.} and Gelman, {Rebecca S.} and Wu, {Alan H B} and Punglia, {Rinaa S.} and Mayer, {Erica L.} and Tolaney, {Sara M.} and Winer, {Eric P.} and Partridge, {Ann H.} and Burstein, {Harold J.}",
year = "2013",
month = "10",
doi = "10.1007/s10549-013-2700-1",
language = "English (US)",
volume = "141",
pages = "421--427",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Personalized medicine in breast cancer

T2 - Tamoxifen, endoxifen, and CYP2D6 in clinical practice

AU - Ruddy, Kathryn J

AU - Desantis, Stephen D.

AU - Gelman, Rebecca S.

AU - Wu, Alan H B

AU - Punglia, Rinaa S.

AU - Mayer, Erica L.

AU - Tolaney, Sara M.

AU - Winer, Eric P.

AU - Partridge, Ann H.

AU - Burstein, Harold J.

PY - 2013/10

Y1 - 2013/10

N2 - Abstract: Tamoxifen is metabolized into endoxifen, a potent antagonist of the estrogen receptor, in part through cytochrome p450 (CYP) 2D6. Genotypic variation in CYP2D6 affects endoxifen levels, and some have argued that patients who do not efficiently metabolize tamoxifen might wish to consider alternative hormonal treatments. This study evaluated an algorithm in which endoxifen levels and CYP2D6 genotypes were used to make hormonal therapy recommendations for patients on adjuvant tamoxifen for breast cancer. Patients with stage I-III breast cancer who had been taking adjuvant tamoxifen for 8-56 weeks were eligible. At enrollment, baseline whole blood and serum were sent for genotyping by Amplichip and endoxifen measurement, respectively, and endoxifen levels were also measured 3 weeks later. Results were returned to oncologists along with an algorithm-generated treatment recommendation. The algorithm recommended that participants with poor metabolizer genotype and/or baseline endoxifen level <6 ng/mL consider alternative endocrine therapy. A medical record review evaluated actual treatment decisions. Of 99 patients on study, 18 (18 %) had findings that triggered algorithm-based recommendations to consider a change in endocrine therapy due to endoxifen <6 ng/mL (all 18 patients) and/or poor metabolizer CYP2D6 genotype (2 of the 18). Endoxifen levels were ≥6 ng/mL in four of them 3 weeks later. Seven (39 % of 18) switched to a different treatment (one based on toxicity, not the algorithm). Hot flash burden was not found to be significantly associated with endoxifen <6 ng/mL or genotype. Prospective testing of tamoxifen metabolism as gauged by CYP2D6 genotype and serum endoxifen levels is feasible. Future studies of tamoxifen metabolism and efficacy should consider including measurement of serial endoxifen levels. Although clinical evidence at present is insufficient to warrant routine CYP2D6 or endoxifen testing, some clinicians and patients did utilize this predefined algorithm to inform clinical decisions regarding optimal adjuvant endocrine therapy.

AB - Abstract: Tamoxifen is metabolized into endoxifen, a potent antagonist of the estrogen receptor, in part through cytochrome p450 (CYP) 2D6. Genotypic variation in CYP2D6 affects endoxifen levels, and some have argued that patients who do not efficiently metabolize tamoxifen might wish to consider alternative hormonal treatments. This study evaluated an algorithm in which endoxifen levels and CYP2D6 genotypes were used to make hormonal therapy recommendations for patients on adjuvant tamoxifen for breast cancer. Patients with stage I-III breast cancer who had been taking adjuvant tamoxifen for 8-56 weeks were eligible. At enrollment, baseline whole blood and serum were sent for genotyping by Amplichip and endoxifen measurement, respectively, and endoxifen levels were also measured 3 weeks later. Results were returned to oncologists along with an algorithm-generated treatment recommendation. The algorithm recommended that participants with poor metabolizer genotype and/or baseline endoxifen level <6 ng/mL consider alternative endocrine therapy. A medical record review evaluated actual treatment decisions. Of 99 patients on study, 18 (18 %) had findings that triggered algorithm-based recommendations to consider a change in endocrine therapy due to endoxifen <6 ng/mL (all 18 patients) and/or poor metabolizer CYP2D6 genotype (2 of the 18). Endoxifen levels were ≥6 ng/mL in four of them 3 weeks later. Seven (39 % of 18) switched to a different treatment (one based on toxicity, not the algorithm). Hot flash burden was not found to be significantly associated with endoxifen <6 ng/mL or genotype. Prospective testing of tamoxifen metabolism as gauged by CYP2D6 genotype and serum endoxifen levels is feasible. Future studies of tamoxifen metabolism and efficacy should consider including measurement of serial endoxifen levels. Although clinical evidence at present is insufficient to warrant routine CYP2D6 or endoxifen testing, some clinicians and patients did utilize this predefined algorithm to inform clinical decisions regarding optimal adjuvant endocrine therapy.

KW - Antineoplastic agents/hormonal

KW - Breast neoplasms

KW - Genotype

KW - Tamoxifen

UR - http://www.scopus.com/inward/record.url?scp=84887062641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887062641&partnerID=8YFLogxK

U2 - 10.1007/s10549-013-2700-1

DO - 10.1007/s10549-013-2700-1

M3 - Article

VL - 141

SP - 421

EP - 427

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -