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New International Practice Guidelines for Using CYP2D6 Genotype to Guide Antiestrogen Treatment in Breast Cancer

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Key Points

  • The consensus of the group was that there was sufficient evidence to use CYP2D6 genotype to assist with clinical recommendations for women who are being considered for tamoxifen for early-stage estrogen receptor–positive breast cancer.
  • A therapeutic recommendation for dosing or use of an alternative hormonal therapy based on CYP2D6 genotype was also included in the guidelines.

An international group of clinicians and scientists representing the Clinical Pharmacogenetics Implementation Consortium (CPIC) published the first-ever clinical practice guidelines for using CYP2D6 genotype to guide tamoxifen therapy. Their research was published by Goetz et al in Clinical Pharmacology and Therapeutics.

Tamoxifen is a hormonal agent used for the prevention and treatment of premenopausal and postmenopausal estrogen receptor–positive breast cancer. CYP2D6 genotype is an inherited factor that alters the metabolism of tamoxifen.

“The goal of the CPIC Guideline for CYP2D6 and tamoxifen therapy is to provide clinicians information that will allow the interpretation of clinical CYP2D6 genotype tests, so that the results can be used to guide prescribing of tamoxifen when genotype information is available,” said lead author Matthew Goetz, MD, medical oncologist at the Mayo Clinic. “The consensus of the consortium tamoxifen group was that there was sufficient evidence to use CYP2D6 genotype to assist with clinical recommendations for women who are being considered for tamoxifen for early-stage estrogen receptor–positive breast cancer.”

Patients with certain CYP2D6 genotypes and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen for early breast cancer.

In the consensus guidelines, an extensive review and grading of the evidence regarding the role of CYP2D6 and tamoxifen clinical outcomes was provided, as well as a therapeutic recommendation for dosing or use of an alternative hormonal therapy based on CYP2D6 genotype.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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