Does genetic test allow prediction of patients’ response to tamoxifen?

Various studies have suggested that a genetic test for the efficacy of the commonly used breast cancer drug, tamoxifen, is an effective predictor of how patients will respond to the drug. Tamoxifen undergoes metabolism upon oral administration, and it is widely accepted that the majority of the anti-proliferative effects of tamoxifen occur via its active metabolites. The CYP2D6 gene plays an important role in these metabolic pathways, and a genetic test is available which establishes which variant of the CYP2D6 gene the patient has. Some experts recommend that this test should be used in clinical practice, particularly in the case of postmenopausal women.

Research published in Breast Cancer Research sheds new light on the matter. The study looked at 6640 breast cancer patients from the United Kingdom and evaluated the association between genotype and breast cancer specific survival (BCSS), finding weak evidence that the poor-metaboliser variant, CYP2D6*6, is associated with decreased BCSS. This suggests that the use of this test in a clinical setting should be avoided until larger studies confirming any associations are available.

There are currently 500,000 women in the U.S.A. taking tamoxifen, so this outcome has the potential to affect hundreds of thousands of people. This fresh evidence reflects recent doubts about the test, as an editorial published recently in the Journal of Clinical Oncology stated that "routine use should await more reliable evidence from well-designed studies."

Anita Bock
Assistant Editor – Breast Cancer Research

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