Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy

Yan Jin, Daniel F. Hayes, Lang Li, Jason D. Robarge, Todd C. Skaar, Santosh Philips, Anne Nguyen, Anne Schott, Jill Hayden, Suzanne Lemler, Anna Maria Storniolo, David A. Flockhart, Vered Stearns

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35 Scopus citations

Abstract

Purpose: Hot flashes are common and frequently lead to drug discontinuation among women prescribed tamoxifen. We determined whether genetic polymorphisms in estrogen receptors (ESRs) α and β (ESR1 and ESR2, respectively) are associated with tamoxifen-induced hot flashes. Patients and Methods: We determined ESR1 PvuII and XbaI and ESR2-02 genotypes in 297 women who were initiating tamoxifen. One-week hot flash diaries were collected to calculate a hot flash score (frequency x severity) before and 1, 4, 8, and 12 months after starting tamoxifen. Results: Approximately 80% of 297 participants reported hot flashes before or during the first year of tamoxifen. After 4 months of tamoxifen, premenopausal women who did not receive adjuvant chemotherapy had a four-fold increase in hot flash score (from 5.9 to 23.6; P = .003) compared with a 1.17-fold increase (from 19.6 to 23; P = .34) in those who received chemotherapy. In premenopausal women, increased number of ESR1 PvuII and XbaI CG alleles was associated with higher baseline hot flash scores compared with those who had other haplotypes (P = .0026). At 4 months, postmenopausal women with ESR1 PvuII CC and ESR2-02 GG genotypes had 4.6 times increases in hot flash scores than other postmenopausal women (56 v 12; P = .0007). Women who had the ESR2-02 AA genotype were significantly less likely to experience tamoxifen-induced hot flashes than women who carried at least one ESR-02 G allele (hazard ratio, 0.26; 95% CI, 0.10 to 0.63; P = .001). Conclusion: Knowledge of menopausal status, prior chemotherapy, and ESR genotype may help predict which women are most likely to suffer hot flashes during tamoxifen treatment.

Original languageEnglish (US)
Pages (from-to)5849-5854
Number of pages6
JournalJournal of Clinical Oncology
Volume26
Issue number36
DOIs
StatePublished - Dec 20 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Jin, Y., Hayes, D. F., Li, L., Robarge, J. D., Skaar, T. C., Philips, S., Nguyen, A., Schott, A., Hayden, J., Lemler, S., Storniolo, A. M., Flockhart, D. A., & Stearns, V. (2008). Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy. Journal of Clinical Oncology, 26(36), 5849-5854. https://doi.org/10.1200/JCO.2008.16.8377