CYP2D6 Variants Linked With Tamoxifen Response

Improved clinical outcomes may be associated with two functional CYP2D6 alleles
By Rick Ansorge
HealthDay Reporter

TUESDAY, Oct. 6 (HealthDay News) -- In patients with early-stage breast cancer undergoing adjuvant tamoxifen treatment, an association may exist between the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme and clinical outcomes, according to a retrospective analysis published in the Oct. 7 issue of the Journal of the American Medical Association.

Werner Schroth, of the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology in Stuttgart, Germany, and colleagues genotyped 1,325 women who were diagnosed between 1986 and 2005 for CYP2D6 variants associated with reduced or absent enzyme activity. Of these patients, CYP2D6 metabolism was described as extensive in 609 patients, heterozygous extensive/intermediate in 637 patients, and poor in 79 patients.

The researchers found that the presence of two functional CYP2D6 alleles was associated with better clinical outcomes than reduced or non-functioning alleles. After a nine-year follow-up, recurrence rates were higher among heterozygous extensive/intermediate or poor metabolizers (20.9 and 29 percent, respectively) than in those with extensive metabolism (14.9 percent). Decreased CYP2D6 activity was associated with poorer event-free survival and disease-free survival (hazard ratios, 1.33 and 1.29, respectively), but not overall survival (hazard ratio, 1.15). In addition, the authors note, there was an increased risk of recurrence for heterozygous extensive/intermediate and poor metabolizers as compared to extensive metabolizers.

"Genotyping has the potential for identification of women who have the CYP2D6 poor metabolism phenotype and for whom the use of tamoxifen is associated with poor outcomes, thus indicating consideration of alternative forms of adjuvant endocrine therapy," the authors conclude.

Several authors reported financial and consulting relationships with pharmaceutical companies.

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