CYP2D6 variants affect breast cancer response to tamoxifen

May 6, 2008

NEW YORK (Reuters Health) - Variations of the cytochrome P450 2D6 (CYP2D6) genotype metabolize tamoxifen differently. Post-menopausal breast cancer patients with homozygous wild-type CYP2D6 may respond as well or better to tamoxifen as they respond to aromatase inhibitor adjuvant therapy, researchers report in the April 29th issue of the Journal of the National Cancer Institute.

"Our model," lead investigator Dr. Rinaa S. Punglia of the Dana Farber Cancer Institute in Boston told Reuters Health, "raises the possibility that tailored therapy based on pharmacogenomics could be considered for post-menopausal women newly diagnosed with breast cancer."

"Especially for women who are concerned about the relative toxicity or cost of an aromatase inhibitor as initial treatment," she added, "one might consider CYP2D6 genetic testing and pursue treatment with tamoxifen if found to be wild-type at CYP2D6."

Dr. Punglia and colleagues used data from randomized trials in their development of a Markov decision model to simulate the clinical histories of hypothetical cohorts of post-menopausal women with hormone receptor-positive invasive breast cancer who were treated with tamoxifen or an aromatase inhibitor.

The researchers found that in women who were homozygous wild type for CYP2D6, adjuvant treatment with tamoxifen appeared to provide 5-year disease-free survival which was similar or perhaps even superior to that with aromatase inhibitors.

These results, they point out, are in contrast to the significantly better results previously seen with aromatase inhibitors in unselected populations.

"This is an exciting result," concluded Dr. Punglia. "It points out that the future of medicine is headed towards individually tailored therapy, where the most effective treatment will be chosen not only on the basis of disease characteristics, but also on the genetic makeup of the particular patient."

In an accompanying editorial, Dr. Daniel F. Hayes of the University of Michigan, Ann Arbor and colleagues agree that this is likely to be the approach, pointing out that in the future, personalized cancer medicine will probably incorporate "both tumor-related somatic changes and inherited germline pharmacogenetic factors to predict the best course of treatment for a specific patient."