title: CYP2D6 genotype in relation to hot flashes as tamoxifen side effect in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial.
abstract: 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.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Vincent O
authors.initials: VO
authors.lastname: Dezentjé
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Ron H N
authors.initials: RH
authors.lastname: Van Schaik
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vletter-Bogaartz
authors.forename: Tahar
authors.initials: T
authors.lastname: Van der Straaten
authors.forename: Judith A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: Elma Meershoek-Klein
authors.initials: EM
authors.lastname: Kranenbarg
authors.forename: Els M
authors.initials: EM
authors.lastname: Berns
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: Van de Velde
authors.forename: Johan W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D019584:Hot Flashes / Q000209:etiology*; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D010641:Phenotype; D017698:Postmenopause; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6