[CYP2D6 polymorphisms and tamoxifen: therapeutic perspectives in the management of hormonodependent breast cancer patients].
Tamoxifen is a prodrug mainly metabolized by the CY2D6 cytochrome. More than 80 variants of the CYP2D6 gene have been identified. They predict four different enzymatic phenotypes: ultra-rapid metabolizers (UM), extensive metabolizers (EM), intermediate metabolizers (IM) and poor metabolizers (PM). Six retrospectives studies suggest a link between some polymorphisms of the CYP2D6 and tamoxifen efficacy and two studies have found no statistically significant data. Today, level of proof remains insufficient to recommend the testing of a patient's genotype before tamoxifen prescription. Designing prospective studies is necessary before considering therapy strategies based on pharmacogenetics data. In pre-menopausal breast cancer PM or IM patients, an increase in dosage of tamoxifen or a treatment with LH-RH analogues with aromatase inhibitors (AI) may be beneficial instead of the actual recommendations of a 5-year tamoxifen therapy. In postmenopausal EM patients, tamoxifen may be as efficient as AI. In post-menopausal PM patients, a switch strategy may be inferior to a 5-year IA strategy, which would therefore be the standard of care.
Barrière
J
J
Département d'oncologie médicale, centre Antoine-Lacassagne, 06189 Nice cedex 02, France.
Formento
J-L
JL
Milano
G
G
Ferrero
J-M
JM
D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D020834:Ethnopharmacology; D005260:Female; D006801:Humans; D008593:Menopause; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011355:Prodrugs; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen; D019389:Cytochrome P-450 CYP2D6