PURPOSE: Hot flashes are common and frequently lead to drug discontinuation among women prescribed tamoxifen. We determined whether genetic polymorphisms in estrogen receptors (ESRs) alpha and beta (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.
PURPOSE: Hot flashes are common and frequently lead to drug discontinuation among women prescribed tamoxifen. We determined whether genetic polymorphisms in estrogen receptors (ESRs) alpha and beta (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.
Authors: Daniel J Schaid; Charles M Rowland; David E Tines; Robert M Jacobson; Gregory A Poland Journal: Am J Hum Genet Date: 2001-12-27 Impact factor: 11.025
Authors: David M Herrington; Timothy D Howard; Gregory A Hawkins; David M Reboussin; Jianfeng Xu; Siqun L Zheng; K Bridget Brosnihan; Deborah A Meyers; Eugene R Bleecker Journal: N Engl J Med Date: 2002-03-28 Impact factor: 91.245
Authors: Brian Leyland-Jones; Kathryn P Gray; Mark Abramovitz; Mark Bouzyk; Brandon Young; Bradley Long; Roswitha Kammler; Patrizia Dell'Orto; Maria Olivia Biasi; Beat Thürlimann; Vernon Harvey; Patrick Neven; Laurent Arnould; Rudolf Maibach; Karen N Price; Alan S Coates; Aron Goldhirsch; Richard D Gelber; Olivia Pagani; Giuseppe Viale; James M Rae; Meredith M Regan Journal: Breast Cancer Res Treat Date: 2015-11-21 Impact factor: 4.872
Authors: J M Rae; M J Sikora; N L Henry; L Li; S Kim; S Oesterreich; T C Skaar; A T Nguyen; Z Desta; A M Storniolo; D A Flockhart; D F Hayes; V Stearns Journal: Pharmacogenomics J Date: 2009-05-05 Impact factor: 3.550
Authors: Daniel L Hertz; N Lynn Henry; Kelley M Kidwell; Dafydd Thomas; Audrey Goddard; Faouzi Azzouz; Kelly Speth; Lang Li; Mousumi Banerjee; Jacklyn N Thibert; Celina G Kleer; Vered Stearns; Daniel F Hayes; Todd C Skaar; James M Rae Journal: Physiol Genomics Date: 2016-08-19 Impact factor: 3.107
Authors: L Weng; D Ziliak; H K Im; E R Gamazon; S Philips; A T Nguyen; Z Desta; T C Skaar; D A Flockhart; R S Huang Journal: Ann Oncol Date: 2013-03-18 Impact factor: 32.976
Authors: N L Henry; A Nguyen; F Azzouz; L Li; J Robarge; S Philips; D Cao; T C Skaar; J M Rae; A M Storniolo; D A Flockhart; D F Hayes; V Stearns Journal: Br J Cancer Date: 2009-12-01 Impact factor: 7.640