Genotype tied to success of breast cancer therapy with tamoxifen

December 7, 2007

NEW YORK (Reuters Health) - Variants in genes CYP2D6 and CYP2C19 encoding P450 enzymes can predict therapy response or failure in patients with estrogen receptor-positive breast cancer treated with tamoxifen, according to German researchers.

"The clinical importance of this finding," senior investigator Dr. Hiltrud Brauch told Reuters Health, "is that genotyping can identify patients likely to benefit from tamoxifen and, moreover, those in need for treatment alternatives -- a result that now calls for verification in large clinical trials."

As reported in the November 20th issue of the Journal of Clinical Oncology, Dr. Brauch of the Institute of Clinical Pharmacology, Stuttgart and colleagues genotyped DNA from 206 patients receiving tamoxifen adjuvant monotherapy and 280 who were not.

The team found that compared with carriers of functional alleles, patients in the tamoxifen group with CYP2D6 alleles *4, *5, *10, and *41 -- all associated with reduced formation of antiestrogenic metabolites -- had significantly more recurrences of breast cancer (hazard ratio, 2.24). They also had shorter relapse-free periods and lower event-free survival rates.

In addition, patients with the CYP2C19 high enzyme activity promoter variant *17 had a more favorable clinical outcome (hazard ratio, 0.45) than carriers of the *1, *2, and *3 alleles.

The finding, continued Dr. Brauch, "holds the potential to overcome the one-drug-fits-all concept and take current decisions on the choice of endocrine treatment to the level of germline polymorphisms. Due to their inherent nature, they are accessible to genotyping from blood and other diagnostic materials independent from disease stage."

"Up-front genetic testing," she concluded, "will support this decision and thereby individualize drug treatment at the earliest stage for a maximum patient benefit."