Jeffrey M. Peppercorn, MD, MPHTamoxifen is generally regarded as the gold-standard drug for preventing breast cancer recurrence in premenopausal women with a prior history of the disease, but there is much individual variation in response.

Jeffrey Peppercorn, MD, Duke medical biologist, bioethicist, and breast cancer specialist, explains that patients differ in their ability to metabolize the drug, which is correlated in some studies with its effectiveness.

That ability to metabolize tamoxifen is linked to genetic differences in the CYP2D6 enzyme. The FDA recently approved a genetic test that may help identify which patients are likely to respond -- but that hasn’t been firmly established.

Such uncertainty is not unusual given the rapid pace of pharmacogenetic research, says Peppercorn. “Pharmacogenetic tests can become available in the marketplace while the evidence on whether to use them or how best to use them in clinic is still evolving.”

Peppercorn and colleague Nicole Kuderer, MD, published a comprehensive review of the evidence in the December 2009 issue of Oncology, concluding that more definitive research about CYP2D6 testing is needed before it can be routinely recommended.

Peppercorn is currently leading a study with colleagues at the University of North Carolina that explores the potential benefits of dosing based on genetic metabolism.

Peppercorn says that how doctors use this type of testing can be as important as the effectiveness of the test itself. He led a survey of oncologists around the country to understand how the CYP2D6 test is currently being used in practice, and found that use of the test remains rare -- but that community-based oncologists are almost twice as likely to order the test as breast cancer specialists.

“It’s another example of why we need to keep oncologists up to date on what we do and don’t yet know about a test’s potential benefits,” Peppercorn says. [At press time he was scheduled to present data at the June 2010 American Society of Clinical Oncology annual meeting on what factors oncologists consider most important when deciding to order a novel genetic test.]

On a broader scale, Duke recently launched a Genetic Testing Advisory Committee; it will provide recommendations to Duke physicians about which of the growing list of genetic tests approved by the FDA to guide drug prescribing should be routinely offered to Duke patients. The committee is among the first of its kind in the nation established by an academic health system.