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Tamoxifen is the generic name for the most widely used of the SERMs in the treatment of breast cancer; it is usually sold under the trade name Nolvadex. Since the expiration of it's patent in 2002, tamoxifen is now widely available in generic form.Wikipedia
Up to 7-10% of women with breast cancer may not receive the full medical benefit from taking tamoxifen, because of their unique genetic make-up. These women have less functional versions of the CYP2D6 gene, which may reduce the effectiveness of tamoxifen and increase their chance of breast cancer recurrence.
On Oct 18, 2006 the Subcommittee for Clinical Pharmacology recommended relabeling tamoxifen to include information about this gene in the package insert.
A 2009 review of several studies since then mostly confirms worse clinical outcome in patients with decreased CYP2D6 metabolism and supports the notion that CYP2D6 genotype may well become a clinically relevant predictive marker.[PMID 19118028]
An additional retrospective study published after this review extended the earlier findings by specifically studying primarily post-menopausal women with early (I-III) stage, ER+/PR+ breast cancer. Based on a median follow-up time of 6 years, this report found that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.[PMID 19809024]
However, an argument has also been made that making conclusions based on such studies is still premature, primarily because there are also over ten studies with "widely heterogeneous results with relative-risk estimates outside the range of reasonable bounds".[PMID 19647203]
A 2010 study has extended the CYP2D6 risk by also pointing to risk associated with SNP rs3740065 in the ABCC2 gene; patients taking tamoxifen who had all 4 risk alleles at these two genes were said to have a 45 fold higher risk of breast cancer recurrence compared to patients with one or less risk alleles. For CYP2D6 alone, carriers of one or two risk alleles had adjusted hazard ratios for recurrence of ~4 fold and ~9 fold, respectively, compared to women with two fully functioning alleles.[PMID 20124171]
Another 2010 study finds a significantly increased risk for thromboembolic events in women who carry a rs6025(A) SNP and who are taking tamoxifen as part of their treatment for breast cancer.[PMID 20554945]