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


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).


CONCLUSIONS
Knowledge of menopausal status, prior chemotherapy, and ESR genotype may help predict which women are most likely to suffer hot flashes during tamoxifen treatment.
Jin
Yan
Y
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Hayes
Daniel F
DF
Li
Lang
L
Robarge
Jason D
JD
Skaar
Todd C
TC
Philips
Santosh
S
Nguyen
Anne
A
Schott
Anne
A
Hayden
Jill
J
Lemler
Suzanne
S
Storniolo
Anna Maria
AM
Flockhart
David A
DA
Stearns
Vered
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006239:Haplotypes; D019584:Hot Flashes / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D011960:Receptors, Estrogen / Q000235:genetics*; D013629:Tamoxifen / Q000009:adverse effects*
D011960:Receptors, Estrogen; D013629:Tamoxifen