Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients.
The selective estrogen receptor modulator tamoxifen is routinely used for treatment and prevention of estrogen-receptor-positive breast cancer. Studies of tamoxifen adherence suggest that over half of patients discontinue treatment before the recommended 5 years. We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen-treated women (n=297) were genotyped for CYP2D6 variants and assigned a 'score' based on predicted allele activities from 0 (no activity) to 2 (high activity). Correlation between CYP2D6 score and discontinuation rates at 4 months was tested. We observed a strong nonlinear correlation between higher CYP2D6 score and increased rates of discontinuation (r(2)=0.935, P=0.018). These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Therefore, patients who may be most likely to benefit from tamoxifen may paradoxically be most likely to discontinue treatment prematurely.
Breast Oncology Program, Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0612, USA. jimmyrae@umich.edu
J M
JM
Rae
M J
MJ
Sikora
N L
NL
Henry
L
L
Li
S
S
Kim
S
S
Oesterreich
T C
TC
Skaar
A T
AT
Nguyen
Z
Z
Desta
A M
AM
Storniolo
D A
DA
Flockhart
D F
DF
Hayes
V
V
Stearns
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D010349:Patient Compliance; D011446:Prospective Studies; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6