Pharmacogenomicsin Primary Care
Testingfor CYP2D6 variants prior to starting tamoxifen for breast cancer
Tamoxifenis one of the therapies that are very effective in handling thebreast cancer disorder. The metabolism of this therapy involvesCYP2D6, which is a phase I enzyme. In most circumstances, some of thevariants of the enzyme lead to poor metabolism of tamoxifen and insuch case, they are hypothesized to minimize their effectiveness.Tamoxifen has handled the ER-positive breast cancer to the requiredstandards for some years, and it has proved to be full of benefits tothe patients. The recurrence rate has decreased significantly and theoverall survival of the patients has improved with time. Likewise,the mortality rate of the breast cancer patients has decreased byalmost one-third.
Metabolismof the tamoxifen takes place after the oral administration. In thecancer patients’ plasma, there is a major metabolite known asN-desmethyl tamoxifen that must undergo secondary metabolism. Forthis conversion to take place, the CYP2D6 must be actively involvedand also take part in changing the tamoxifen to 4-hydroxy tamoxifen(Abraham et al, 2010).
Thevariations of the CYP2D6 metabolism are closely connected to theclinical outcomes of tamoxifen in the patients, who have the breastcancer condition although however, the data available concerning theenzyme metabolism and the prevention of this disorder is veryminimal. Some other data advocates that there is no relationshipbetween the tamoxifen metabolites and its efficiency in theprevention of breast cancer. The role of the estrogen receptormodulators chemoprevention should emphasize on the global geneticvariation without giving any part priority of establishing whetherthe development of cancer is associated with it (Goetz et al, 2011).
Thereare several issues surrounding the use of enzyme CYP2D6 in theclinical setting while dealing with the breast cancer pandemic amongmost women. The effect of the enzyme on the tamoxifen therapy is notyet clear in fact, there is no quality data that can justify thisassertion. Similarly, the testing of the CYP2D6 poses some risks onthe different categories of women, like those who are past menopause.Likewise, in as far as the medication of CYP2D6 is needed in order torespond to breast cancer, no modifications have been identified yet.It is possible to conclude that the lack of evidence disqualifiesCYP2D6 genotyping from guiding the treatment of tamoxifen.
Therefore,in any medication that is aimed at the treatment of breast cancer,the testing of the CYP2D6 is paramount this will help understand theeffect it has on the efficiency of the tamoxifen while it is used asan intervention for this disorder.
Inthe case where I may be working as the prescribing primary careprovider, there are several implications that I can make regardingthe use of CYP2D6 in connection to the tamoxifen while dealing withthe breast cancer disorder in women. For instance, I can concludethat the enzyme CYP2D6 genotype and the tamoxifen responses are notrelated in any manner and, therefore, they can be administered to thepatient. This is because several studies that have been carried outhave not found any effect of tamoxifen therapy that can be attributedto CYP2D6 enzyme. I can comfortably administer the two responses buttake caution since any possible effect may emerge as a result of thisaction. As the provider, I will observe the necessary precautionseven though the criticism that has been put across cannot bejustified (Woo and Wynne, 2011).
Abrahamet al. (2010). CYP2D6Gene Variants: Association with Breast Cancer Specific Survival in aCohort of Breast Cancer Patients from the United Kingdom Treated withAdjuvant Tamoxien,Retrieved fromhttp://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2629on June 8, 2016
Goetzet al. (2011). Evaluationof CYP2D6 and Efficiency of Tamoxifen and Raloxifene in Women Treatedfor Breast Cancer Chemoprevention: Results from the NSABP P1 and P2Clinical Trials,Retrieved fromhttp://clincancerres.aacrjournals.org/content/17/21/6944.fullon June 8, 2016
Woo,T.M & Wynne, A.L. (2011). Pharmacotherapeuticsfor Nurse Practitioner Prescribers.F.A: Davis Company Publishers.