In
tamoxifen-treated
breast cancer patients the occurrence of
hot flashes may be associated with effective
estrogen receptor antagonism dependent on genetic variations of metabolic
enzymes and the
estrogen receptor. Early
breast cancer patients who were randomized to receive
tamoxifen, followed by
exemestane within the
tamoxifen exemestane adjuvant multinational trial were genotyped for five
CYP2D6 alleles.
CYP2D6 genotypes and phenotypes were related to the occurrence of
hot flashes as adverse event during the first year of
tamoxifen use (primary aim) and the time to the occurrence of
hot flashes as AE during the complete time on
tamoxifen (secondary aim). In addition, exploratory analyses on 22 genetic variants of other metabolic
enzymes and two common polymorphisms in the
estrogen receptor-1 were performed. No association was found between the
CYP2D6 genotype/phenotype or any other genetic variant and
hot flashes during the first year. Only higher age was related to a lower incidence of
hot flashes in the first year (adjusted odds ratio 0.94, 95 % CI 0.92-0.96; p < 0.001). The ESR1 PvuII XbaI CG haplotype was associated with the time to the occurrence of
hot flashes during the complete time on
tamoxifen (CG/CG vs. CG/other + other/other: adjusted hazard ratio 0.49, 95 % CI 0.25-0.97; p = 0.04). In conclusion, the
CYP2D6 genotypes and phenotypes were not associated with the occurrence of
hot flashes. Common polymorphisms in the
estrogen receptor-1 might predict
hot flashes as common
tamoxifen side effect, although this finding needs replication.