Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

Kathryn J. Ruddy; Daniel J. Schaid; Ann H. Partridge; Nicholas B. Larson; Anthony Batzler; Lothar Häberle; Ralf Dittrich; Peter Widschwendter; Visnja Fink; Emanuel Bauer; Judith Schwitulla; Matthias Rübner; Arif B. Ekici; Viktoria Aivazova-Fuchs; Elizabeth A. Stewart; Matthias W. Beckmann; Elizabeth Ginsburg; Liewei Wang; Richard M. Weinshilboum; Fergus J. Couch; Wolfgang Janni; Brigitte Rack; Celine Vachon; Peter A. Fasching

doi:10.1016/j.fertnstert.2019.05.018

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

Kathryn J. Ruddy, Daniel J. Schaid, Ann H. Partridge, Nicholas B. Larson, Anthony Batzler, Lothar Häberle, Ralf Dittrich, Peter Widschwendter, Visnja Fink, Emanuel Bauer, Judith Schwitulla, Matthias Rübner, Arif B. Ekici, Viktoria Aivazova-Fuchs, Elizabeth A. Stewart, Matthias W. Beckmann, Elizabeth Ginsburg, Liewei Wang, Richard M. Weinshilboum, Fergus J. CouchWolfgang Janni, Brigitte Rack, Celine Vachon, Peter A. Fasching

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Objective: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Design: Genome-wide association study. Setting: Not applicable. Patient(s): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. Intervention(s): None. Main Outcome Measure(s): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. Result(s): The median age of the 1,168 women was 41 years (range 19–45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5′ upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Conclusion(s): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

Original language	English (US)
Pages (from-to)	731-739.e1
Journal	Fertility and sterility
Volume	112
Issue number	4
DOIs	https://doi.org/10.1016/j.fertnstert.2019.05.018
State	Published - Oct 2019

Keywords

Breast neoplasms
amenorrhea
drug therapy
toxicity

ASJC Scopus subject areas

Reproductive Medicine
Obstetrics and Gynecology

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10.1016/j.fertnstert.2019.05.018

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Ruddy, K. J., Schaid, D. J., Partridge, A. H., Larson, N. B., Batzler, A., Häberle, L., Dittrich, R., Widschwendter, P., Fink, V., Bauer, E., Schwitulla, J., Rübner, M., Ekici, A. B., Aivazova-Fuchs, V., Stewart, E. A., Beckmann, M. W., Ginsburg, E., Wang, L., Weinshilboum, R. M., ... Fasching, P. A. (2019). Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer. Fertility and sterility, 112(4), 731-739.e1. https://doi.org/10.1016/j.fertnstert.2019.05.018

Ruddy, KJ , Schaid, DJ, Partridge, AH, Larson, NB, Batzler, A, Häberle, L, Dittrich, R, Widschwendter, P, Fink, V, Bauer, E, Schwitulla, J, Rübner, M, Ekici, AB, Aivazova-Fuchs, V, Stewart, EA, Beckmann, MW, Ginsburg, E, Wang, L , Weinshilboum, RM , Couch, FJ, Janni, W, Rack, B, Vachon, C & Fasching, PA 2019, 'Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer', Fertility and sterility, vol. 112, no. 4, pp. 731-739.e1. https://doi.org/10.1016/j.fertnstert.2019.05.018

@article{32a748afc86640b584c893d438794845,

title = "Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer",

abstract = "Objective: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Design: Genome-wide association study. Setting: Not applicable. Patient(s): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. Intervention(s): None. Main Outcome Measure(s): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. Result(s): The median age of the 1,168 women was 41 years (range 19–45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5′ upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Conclusion(s): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.",

keywords = "Breast neoplasms, amenorrhea, drug therapy, toxicity",

author = "Ruddy, {Kathryn J.} and Schaid, {Daniel J.} and Partridge, {Ann H.} and Larson, {Nicholas B.} and Anthony Batzler and Lothar H{\"a}berle and Ralf Dittrich and Peter Widschwendter and Visnja Fink and Emanuel Bauer and Judith Schwitulla and Matthias R{\"u}bner and Ekici, {Arif B.} and Viktoria Aivazova-Fuchs and Stewart, {Elizabeth A.} and Beckmann, {Matthias W.} and Elizabeth Ginsburg and Liewei Wang and Weinshilboum, {Richard M.} and Couch, {Fergus J.} and Wolfgang Janni and Brigitte Rack and Celine Vachon and Fasching, {Peter A.}",

note = "Funding Information: K.J.R. has nothing to disclose. D.J.S. has nothing to disclose. A.H.P. has nothing to disclose. N.B.L. has nothing to disclose. A.B. has nothing to disclose. L.H. has nothing to disclose. R.D. has nothing to disclose. P.W. has nothing to disclose. V.F. has nothing to disclose. E.B. has nothing to disclose. J.S. has nothing to disclose. M.R. has nothing to disclose. A.B.E. has nothing to disclose. V.A.-F. has nothing to disclose. E.A.S. reports a consulting or advisory role with AbbVie, Bayer, Myovant, and Allergan (unrelated to this work) and royalties from UpToDate and Med Learning Group. M.W.B. has nothing to disclose. E.G. reports patents, royalties, or other intellectual property from UptoDate and Springer, providing expert testimony for Adler and Cohen, and receiving research funding from Serono (all unrelated to this work). L.W. has nothing to disclose. R.M.W. has nothing to disclose. F.J.C. has nothing to disclose. W.J. has nothing to disclose. B.R. has nothing to disclose. C.V. has nothing to disclose. P.A.F. reports National Human Genome Research Institute funding relevant to this work, and honoraria from and a consulting or advisory role with Novartis, Roche, Amgen, Celgene, and Pfizer (unrelated to this work).Supported by Clinical and Translational Science Awards KL2TR000136–09 and KL2TR002379 from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health (NIH). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. In addition, grant funding for SUCCESS-A genotyping and quality control came from GARNET (Genomics and Randomized Trials Network): U01HG004438, U01HG005137, U01HG005157. Genotyping of SUCCESS-C was funded in part by the Breast Cancer Research Foundation. These funding sources had no involvement in study design, collection, analysis, interpretation of data, writing, or decision to submit this article for publication. Funding Information: Supported by Clinical and Translational Science Awards KL2TR000136–09 and KL2TR002379 from the National Center for Advancing Translational Sciences , a component of the National Institutes of Health (NIH). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. In addition, grant funding for SUCCESS-A genotyping and quality control came from GARNET (Genomics and Randomized Trials Network): U01HG004438 , U01HG005137 , U01HG005157 . Genotyping of SUCCESS-C was funded in part by the Breast Cancer Research Foundation . These funding sources had no involvement in study design, collection, analysis, interpretation of data, writing, or decision to submit this article for publication. Publisher Copyright: {\textcopyright} 2019 American Society for Reproductive Medicine",

year = "2019",

month = oct,

doi = "10.1016/j.fertnstert.2019.05.018",

language = "English (US)",

volume = "112",

pages = "731--739.e1",

journal = "Fertility and Sterility",

issn = "0015-0282",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

AU - Ruddy, Kathryn J.

AU - Schaid, Daniel J.

AU - Partridge, Ann H.

AU - Larson, Nicholas B.

AU - Batzler, Anthony

AU - Häberle, Lothar

AU - Dittrich, Ralf

AU - Widschwendter, Peter

AU - Fink, Visnja

AU - Bauer, Emanuel

AU - Schwitulla, Judith

AU - Rübner, Matthias

AU - Ekici, Arif B.

AU - Aivazova-Fuchs, Viktoria

AU - Stewart, Elizabeth A.

AU - Beckmann, Matthias W.

AU - Ginsburg, Elizabeth

AU - Wang, Liewei

AU - Weinshilboum, Richard M.

AU - Couch, Fergus J.

AU - Janni, Wolfgang

AU - Rack, Brigitte

AU - Vachon, Celine

AU - Fasching, Peter A.

N1 - Funding Information: K.J.R. has nothing to disclose. D.J.S. has nothing to disclose. A.H.P. has nothing to disclose. N.B.L. has nothing to disclose. A.B. has nothing to disclose. L.H. has nothing to disclose. R.D. has nothing to disclose. P.W. has nothing to disclose. V.F. has nothing to disclose. E.B. has nothing to disclose. J.S. has nothing to disclose. M.R. has nothing to disclose. A.B.E. has nothing to disclose. V.A.-F. has nothing to disclose. E.A.S. reports a consulting or advisory role with AbbVie, Bayer, Myovant, and Allergan (unrelated to this work) and royalties from UpToDate and Med Learning Group. M.W.B. has nothing to disclose. E.G. reports patents, royalties, or other intellectual property from UptoDate and Springer, providing expert testimony for Adler and Cohen, and receiving research funding from Serono (all unrelated to this work). L.W. has nothing to disclose. R.M.W. has nothing to disclose. F.J.C. has nothing to disclose. W.J. has nothing to disclose. B.R. has nothing to disclose. C.V. has nothing to disclose. P.A.F. reports National Human Genome Research Institute funding relevant to this work, and honoraria from and a consulting or advisory role with Novartis, Roche, Amgen, Celgene, and Pfizer (unrelated to this work).Supported by Clinical and Translational Science Awards KL2TR000136–09 and KL2TR002379 from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health (NIH). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. In addition, grant funding for SUCCESS-A genotyping and quality control came from GARNET (Genomics and Randomized Trials Network): U01HG004438, U01HG005137, U01HG005157. Genotyping of SUCCESS-C was funded in part by the Breast Cancer Research Foundation. These funding sources had no involvement in study design, collection, analysis, interpretation of data, writing, or decision to submit this article for publication. Funding Information: Supported by Clinical and Translational Science Awards KL2TR000136–09 and KL2TR002379 from the National Center for Advancing Translational Sciences , a component of the National Institutes of Health (NIH). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. In addition, grant funding for SUCCESS-A genotyping and quality control came from GARNET (Genomics and Randomized Trials Network): U01HG004438 , U01HG005137 , U01HG005157 . Genotyping of SUCCESS-C was funded in part by the Breast Cancer Research Foundation . These funding sources had no involvement in study design, collection, analysis, interpretation of data, writing, or decision to submit this article for publication. Publisher Copyright: © 2019 American Society for Reproductive Medicine

PY - 2019/10

Y1 - 2019/10

N2 - Objective: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Design: Genome-wide association study. Setting: Not applicable. Patient(s): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. Intervention(s): None. Main Outcome Measure(s): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. Result(s): The median age of the 1,168 women was 41 years (range 19–45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5′ upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Conclusion(s): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

AB - Objective: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Design: Genome-wide association study. Setting: Not applicable. Patient(s): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. Intervention(s): None. Main Outcome Measure(s): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. Result(s): The median age of the 1,168 women was 41 years (range 19–45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5′ upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Conclusion(s): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.

KW - Breast neoplasms

KW - amenorrhea

KW - drug therapy

KW - toxicity

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U2 - 10.1016/j.fertnstert.2019.05.018

DO - 10.1016/j.fertnstert.2019.05.018

M3 - Article

C2 - 31371054

AN - SCOPUS:85069858245

SN - 0015-0282

VL - 112

SP - 731-739.e1

JO - Fertility and Sterility

JF - Fertility and Sterility

IS - 4

ER -

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

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Keywords

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