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

Kathryn J. Ruddy, Daniel J. Schaid, A. H. Partridge, Nicholas B. Larson, Anthony Batzler, Lothar Häberle, Ralf Dittrich, P. 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 journalArticle

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 languageEnglish (US)
JournalFertility and Sterility
DOIs
StateAccepted/In press - Jan 1 2019

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Amenorrhea
Breast Neoplasms
Drug Therapy
Menstruation
Phosphopantothenoyl-cysteine decarboxylase
Tamoxifen
Pseudogenes
Genome-Wide Association Study
Gonadotropin-Releasing Hormone
Introns
Single Nucleotide Polymorphism
Decision Making
Outcome Assessment (Health Care)

Keywords

  • amenorrhea
  • Breast neoplasms
  • drug therapy
  • toxicity

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer. / Ruddy, Kathryn J.; Schaid, Daniel J.; Partridge, A. H.; Larson, Nicholas B.; Batzler, Anthony; Häberle, Lothar; Dittrich, Ralf; Widschwendter, P.; Fink, Visnja; Bauer, Emanuel; Schwitulla, Judith; Rübner, Matthias; Ekici, Arif B.; Aivazova-Fuchs, Viktoria; Stewart, Elizabeth A.; Beckmann, Matthias W.; Ginsburg, Elizabeth; Wang, Liewei; Weinshilboum, Richard M.; Couch, Fergus J.; Janni, Wolfgang; Rack, Brigitte; Vachon, Celine; Fasching, Peter A.

In: Fertility and Sterility, 01.01.2019.

Research output: Contribution to journalArticle

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. https://doi.org/10.1016/j.fertnstert.2019.05.018
Ruddy, Kathryn J. ; Schaid, Daniel J. ; Partridge, A. H. ; Larson, Nicholas B. ; Batzler, Anthony ; Häberle, Lothar ; Dittrich, Ralf ; Widschwendter, P. ; Fink, Visnja ; Bauer, Emanuel ; Schwitulla, Judith ; Rübner, Matthias ; Ekici, Arif B. ; Aivazova-Fuchs, Viktoria ; Stewart, Elizabeth A. ; Beckmann, Matthias W. ; Ginsburg, Elizabeth ; Wang, Liewei ; Weinshilboum, Richard M. ; Couch, Fergus J. ; Janni, Wolfgang ; Rack, Brigitte ; Vachon, Celine ; Fasching, Peter A. / Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer. In: Fertility and Sterility. 2019.
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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.",
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T1 - Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

AU - Ruddy, Kathryn J.

AU - Schaid, Daniel J.

AU - Partridge, A. H.

AU - Larson, Nicholas B.

AU - Batzler, Anthony

AU - Häberle, Lothar

AU - Dittrich, Ralf

AU - Widschwendter, P.

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.

PY - 2019/1/1

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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.

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KW - Breast neoplasms

KW - drug therapy

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