CYP2D6 genotype in relation to hot flashes as tamoxifen side effect in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial

• Published in: Breast cancer research and treatment 2014-01, Vol.143 (1), p.171-179
• Main Authors: Dezentjé, Vincent O., Gelderblom, Hans, Van Schaik, Ron H. N., Vletter-Bogaartz, Judith M., Van der Straaten, Tahar, Wessels, Judith A. M., Kranenbarg, Elma Meershoek-Klein, Berns, Els M., Seynaeve, Caroline, Putter, Hein, Van de Velde, Cornelis J. H., Nortier, Johan W. R., Guchelaar, Henk-Jan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Breast cancer; Breast Neoplasms - complications; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Cancer research; Cancer therapies; Chemotherapy, Adjuvant; Cohort Studies; Complications and side effects; Cytochrome P-450; Cytochrome P-450 CYP2D6 - genetics; Drug therapy; Epidemiology; Estrogen; Female; Genetic aspects; Genetic polymorphisms; Genetics; Genotype; Hot Flashes - etiology; Humans; Loss of Heterozygosity; Medicine; Medicine & Public Health; Menopause; Middle Aged; Netherlands; Odds Ratio; Oncology; Phenotype; Postmenopause; Side effects; Tamoxifen; Tamoxifen - adverse effects; Tamoxifen - therapeutic use
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-013-2777-6

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