Wednesday, September 21, 2011

The Latest Research on CYP2D6 Variations for Women on Tamoxifen

Do CYP2D6 variations matter for women on tamoxifen? Variations may affect how women metabolize tamoxifen, but do they make a difference in breast cancer recurrence or prevention? Recent studies suggest maybe not. Today we'll share the latest news and research on how CYP2D6 variations affect women on tamoxifen.

Background from the Dr. Susan Love Research Foundation

An overview from the Dr. Susan Love Research Foundation provides a nice background to the issue. Essentially, a gene called cytochrome P450 2D6 generates an enzyme called CYP2D6. Variations in the gene affect the enzyme production and affect how well a woman metabolizes, or processes tamoxifen. Some women process it better than others.

A 2007 study suggested that women with a certain variation were almost twice as likely to have their cancer recur. Subsequently, some specialists started recommending CYP2D6 testing before starting tamoxifen.

Later studies, however, found that variations in CYP2D6 made no difference in breast cancer recurrence. Dr. Love's website notes that more studies are needed to resolve the inconsistency in the research.

The Latest Research

Dr. Love's website was updated in January 2011. What has happened since then? Studies on CYP2D6 and tamoxifen continue to trickle in. Today we'll share the latest research. Links to all of the studies discussed below may be found on the CYP2D6 testing page of our website.

CYP2D6 variations when tamoxifen is prescribed for prevention

Tamoxifen is sometimes prescribed to prevent breast cancer in women at high-risk. An August 31 study in Clinical Cancer Research found that CYP2D6 variations made no difference in whether or not tamoxifen or Evista (raloxifene) were effective when taken to prevent breast cancer.

CYP2D6 variations when tamoxifen is prescribed to prevent recurrence.

Tamoxifen is also prescribed to prevent recurrence in women treated for breast cancer. Since January 2011, three studies have suggested that CYP2D6 variations make no difference in breast cancer recurrence rates for women on tamoxifen.

A January 15 study in the Journal of the National Cancer Institute from Denmark found, "The association between CYP2D6 inhibition and recurrence in tamoxifen-treated patients is likely null or small."

In a March 25 study in Breast Cancer Research and Treatment from Korea, CYP2D6 variations were not associated with clinical outcomes, such as recurrence, in early-stage breast cancer patients treated with tamoxifen.

Most recently, an August 5 MD Anderson study in Cancer found "no significant effect of CYP2D6 genotype on risk of recurrence in breast cancer patients who received adjuvant tamoxifen therapy."

Current Recommendations

Due to the current state of research, the 2011 National Comprehensive Cancer Network (NCCN) Guidelines do recommend CY2D6 testing for evaluating treatment with tamoxifen. (See March 21 article.)

In Europe, according to the 2011 St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, "The Panel was almost unanimous in rejecting CYP2D6 testing to dictate choice of endocrine therapy type." In the UK, a cost/benefit analysis in the September issue of Health Technology Assessment concluded that CYP2D6 testing could not be recommended at this time due to the rapidly evolving research and limited and conflicting data.

At, we'll continue to follow the research in CYP2D6 testing and tamoxifen. We'll add any developments to our website and database and highlight them in this blog. Please stay tuned.

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