title: Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort.
abstract: Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women initiating tamoxifen. We performed CYP2D6 genotyping using the AmpliChip CYP450 test and correlated inherited genetic polymorphisms in CYP2D6 and tamoxifen-induced hot flashes. Intermediate metabolizers had greater mean hot flash scores after 4 months of tamoxifen therapy (44.3) compared to poor metabolizers (20.6, P = 0.038) or extensive metabolizers (26.9, P = 0.011). At 4 months, we observed a trend toward fewer severe hot flashes in poor metabolizers compared to intermediate plus extensive metabolizers (P = 0.062). CYP2D6 activity may be a modest predictive factor for tamoxifen-induced hot flashes. The presence or absence of hot flashes should not be used to determine tamoxifen's efficacy.
authors.affiliation: Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA, norahh@med.umich.edu.
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Faouzi
authors.initials: F
authors.lastname: Azzouz
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.forename: Zereunesay
authors.initials: Z
authors.lastname: Desta
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sikora
authors.forename: Santosh
authors.initials: S
authors.lastname: Philips
authors.forename: Anne T
authors.initials: AT
authors.lastname: Nguyen
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Storniolo
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000517:prevention & control; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019584:Hot Flashes / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D013629:Tamoxifen / Q000009:adverse effects*
chemical_list: D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6