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Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial.

Abstract

BACKGROUND
Several studies have reported discordant results regarding the impact of the CYP2D6 phenotype on both the effectiveness and the degree of endocrine symptoms associated with tamoxifen. Other studies have suggested that menopausal symptoms may be a predictive factor to tamoxifen response.
METHODS
We investigated the relationship between the CYP2D6-predicted phenotype and tamoxifen response in a nested case-control study among women from the International Breast cancer Intervention Study (IBIS-I), which evaluated tamoxifen in the preventive setting.
RESULTS
In this retrospective analysis of the tamoxifen-treated women in the IBIS-I study, 9 women (16.6%) who developed oestrogen receptor-positive invasive breast cancer had a 2D6 poor or intermediate metaboliser phenotype compared with 45 (20.6%) controls. Adjusted matched logistic regression revealed no significant difference between cases and controls for extensive vs intermediate metaboliser phenotype (OR=0.81 (0.30-2.23), P=0.7) or extensive vs poor metaboliser phenotype (OR=1.02 (0.31-3.32), P=0.9). Controls in the tamoxifen group with a poor metaboliser phenotype developed nonsignificantly fewer hot flushes compared with those with an extensive metaboliser phenotype (OR=0.40 (0.12-1.31)), but those with the intermediate phenotype developed nonsignificantly more hot flushes (OR=1.38 (0.58-3.29)) in an unadjusted analysis.
CONCLUSION
Data from the preventive IBIS-I study did not support an association between the CYP2D6 phenotype and breast cancer outcome or the development of endocrine symptoms in tamoxifen-treated women.

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  • Publisher Full Text

    • Authors

    Sestak I, Kealy R, Nikoloff M, Fontecha M, Forbes JF, Howell A, Cuzick J

    Institution

    Centre for Cancer Prevention, Queen Mary University of London, Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ, UK. i.sestak@qmul.ac.uk

    Source

    British journal of cancer 107:2 2012 Jul 10 pg 230-3

    MeSH

    Adult
    Aged
    Antineoplastic Agents, Hormonal
    Breast Neoplasms
    Case-Control Studies
    Cytochrome P-450 CYP2D6
    Double-Blind Method
    Female
    Follow-Up Studies
    Genetic Predisposition to Disease
    Hot Flashes
    Humans
    Intervention Studies
    Middle Aged
    Phenotype
    Polymorphism, Genetic
    Retrospective Studies
    Tamoxifen

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    22735900