Running head: PHARMACOGENETICS
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Pharmacogenetics of Tamoxifen
Ju Choi
Belmont University
PHARMACOGENETICS
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Pharmacogenetics of Tamoxifen
As people live, it is inevitable for them not to come across a medication in their lives.
Medication helps treat many diseases that people are susceptible to in their lives. Simultaneously,
it could harm people because every person is unique, and their reaction to the medication is
different. That is why pharmacogenetic is so important.
According to the NSW Government (2020), pharmacogenetic is "the study of genetic
factors that influence how a drug works in the body." The pharmacogenetic aims to help
understand the individualized response and the effect on the drug that will allow more effective
treatment and better therapeutic outcomes while reducing side effects (NSW Government, 2020).
This paper will discuss specifically on the Tamoxifen drug, the implication of pharmacogenetic
on Tamoxifen, and the effect of individual variations on this drug.
Drug Information
Tamoxifen is a drug prescribed to treat estrogen receptor positive breast cancer for both
men and women (Breastcancernow, 2020). Breast cancer is considered an estrogen receptor
positive when the malignant cells need estrogen to grow and develop (Komen, 2020).
Tamoxifen is classified as an antiestrogen medication that counteracts breast cancer by
preventing estrogen from attaching to the receptors (U. S. National Library of Medicine, 2020).
Accordingly, Tamoxifen is prescribed for various reasons for the patient diagnosed with
"primary breast cancer, recurrence, or secondary breast cancer"(Breastcancernow, 2020). It is
also prescribed to decrease the chances of breast cancer developing among women at higher risk
due to their family history (Breastcancernow, 2020).
Tamoxifen's therapeutic effect includes a reduced risk of reoccurrence of breast cancer,
secondary breast cancer, breast cancer size, and death from breast cancer (Komen, 2020).
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According to the Breastcancer.org (2020), it decreases the reoccurrence of breast cancer by "40%
to 50% in postmenopausal women and by 30% to 50% in premenopausal women." Also, it
reduces the risk of secondary breast cancer by "about 50%" (Breastcancer.org, 2020). Moreover,
it lowers the risk of women at higher risk of developing breast cancer by about "50%". (National
Cancer Institute, 2020). In addition to this, Tamoxifen can help the body sustain bone density,
which lessens the risk of osteoporosis, fractures in postmenopausal women and enhance the
cholesterol level by lowering LDL (Komen, 2020). The nurse will most likely not be able to
know the therapeutic effect in a patient who takes Tamoxifen immediately because the
Tamoxifen is usually taken for 5 to 10 years to receive the most effective therapeutic results
(Cancer Research UK, 2020). However, the patients will have follow-up appointments where the
doctors and nurses can monitor their progress by blood tests and mammograms (Cancer
Research UK, 2020).
Tamoxifen's common adverse effects are hot flashes, increased bone or cancer pains,
fatigue, nausea, mood swings, constipation, thinning of hair, depression, weight loss, stomach
cramps, headache, and loss of sexual desire (U. S. National Library of Medicine, 2020). Some
severe adverse effects include stroke, blood clots, and endometrial cancer (Breastcancer.org,
2020). Moreover, it could increase the risk of liver cancer and cataracts (U. S. National Library
of Medicine, 2020). Women can especially experience abnormal vaginal discharge, changes to
their periods, and a negative impact on pregnancy (Breastcancernow.org, 2020). Some people
might experience other side effects not listed in this list, so it is important to notify the doctors of
any abnormal symptoms when taking Tamoxifen (U. S. National Library of Medicine, 2020).
There are many adverse effects of Tamoxifen but choosing to take Tamoxifen means that the
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benefit of treatment exceeds the risks and side effects, and it is more significant for the patient
who has breast cancer. (U. S. National Library of Medicine, 2020).
Pharmacogenetic implications
CYP2D6, a specific CY450 enzyme in the body, is mainly responsible for metabolizing
Tamoxifen into an active form, endoxifen (Dean, 2019). There are other CYP enzymes involved
in tamoxifen metabolism include "CYP2C9, CYP2C19, CYP2B6, CYP3A4, and CYP3A5,” but
CYP2D6 is the most critical enzyme to examine (Dean, 2019). Since CYP2D6 is a family of
CY450, it makes them highly polymorphic with over "100 known allelic variants" (Goetz et al.,
2018). Considerably, CYP2D6 is only linked to variation in drug metabolism and response, not
other diseases (Goetz et al., 2018).
The variants in the gene CYP2D6 may influence an individual's CYP2DY activity to
become "increased ('ultrarapid metabolizer'), decreased ('intermediate metabolizer'), or absent
('poor metabolizer')" (Dean, 2019). This affects the level of concentrations of endoxifen available
in the body and prevents an individual from receiving the full benefit from Tamoxifen
medication (Dean, 2019). Some studies revealed that individuals who are poor metabolizers of
CYP2D6 had an increased risk of breast cancer reoccurrence by "2–3 fold” (Goetz et al., 2018).
Moreover, in other studies of populations with a high rate of intermediate metabolizer of
CYP2D6 discovered that they received "less benefit from Tamoxifen and poorer disease-free
survival " (Dean, 2019).
Depending on the individual’s CYP2D6 phenotype, the course of treatment may be
changed. For an individual that is a poor metabolizer of CYP2D6, the CPIC guideline
recommends alternative medication such as an aromatase inhibitor other than Tamoxifen (Goetz
et al., 2018). However, if using aromatase inhibitor is contraindicated, a higher dose of
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Tamoxifen 40 mg per day might be prescribed (Goetz et al., 2018). An individual that is a normal
metabolizer of CYP2D6 will take a normal dose of Tamoxifen 20 mg/day (Goetz et al., 2018).
Individual Variation
Genetic variation in CYP2D6 can be dependent on the ethnicity of individuals. The
alleles that make the nonfunctioning CYP2D6 is more common in Caucasians (Dean, 2019). In
comparison, the alleles that decrease the function of CYP2D6 are much prevalent in Asians and
Africans (Dean, 2019). Statistically, people from North African, Ethiopian, and Saudi heritage
have"16–28 %" more likely to be ultra-rapid metabolizers of CYP2D6, whereas Caucasian
individuals estimate only about "1-10%" (Dean, 2019). Additionally, roughly "6–10%" of
European Caucasians are poor metabolizers. Moreover, about "30%" of Asian descent are
intermediate metabolizers of CYP2D6 (Dean, 2019).
Furthermore, an individual's age affects the treatment of Tamoxifen. Age is relevant for
women because it determines their menopausal status. For younger women who are still
premenopausal, Tamoxifen is prescribed alone or sometimes alongside with ovarian suppression
medication (Breastcancernow.org, 2020). Moreover, how Tamoxifen is prescribed for the second
5 years of treatment would be decided by the woman's menopausal status (Breastcancer.org,
2020). For example, premenopausal and perimenopausal women can continue taking Tamoxifen
for another 5 years (breastcancer.org, 2020). However, postmenopausal women have the option
to continue taking Tamoxifen or change to aromatase inhibitors medication for the next 5 years
(Breastcancer.org, 2020). Similarly, most doctors would recommend prescribing aromatase
inhibitor medication than Tamoxifen for postmenopausal women (National Cancer Institute,
2020).
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Lastly, an individual's medical condition can affect Tamoxifen's use, and specific
medication to treat the medical condition can prevent Tamoxifen's effectiveness. If individual has
medical problems of blood clot such as deep vein thrombosis and pulmonary embolism should
not take Tamoxifen (Mayo Clinic, 2020). Tamoxifen can increase the blood clot problem, and
anticoagulant medicine such as warfarin can interfere with Tamoxifen (breastcancernow.org,
2020). Moreover, a patient taking antidepressant medication should consult with the doctors
because many antidepressant medications are considered selective serotonin reuptake inhibitors,
which block the activity of CYP2D6 (National Cancer Institute, 2020). The patients who are
taking Tamoxifen should review the use of all other medications and medical conditions with the
doctors and avoid drugs that are recognized as strong and moderate inhibitors of CYP2D6 to aid
the effectiveness of Tamoxifen (Breastcancer.org, 2020).
Conclusion
This information is important for the nurses because it supports the information required
to care for and treat each patient. It prepares nurses for what to look for and may keep patients
safer. Medication is a big part of the treatment for different patients and should not be managed
as a uniformed process. Every patient's response to a drug is unique and different, so nurses
should appropriately apply it to adjust to each individual's needs and implement patient-centered
care even for medication. The nurse's understanding of pharmacogenetics will tremendously
impact patient care because it is key to allowing nurses to develop a more personalized and
effective approach for using drugs to improve patients' health while protecting them from
needless harm..
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References
Breastcancer.org. (2020, March 28). Tamoxifen: Uses, Side Effects, and More.
https://www.breastcancer.org/treatment/hormonal/serms/tamoxifen
Breastcancernow. (2020, April 15). Tamoxifen: Hormone therapy drugs | Breast Cancer Care.
https://breastcancernow.org/information-support/facing-breast-cancer/going-throughtreatment-breast-cancer/hormone-therapy/tamoxifen#contraception
Cancer Research UK. (2019, March 19). General Cancer information: Tamoxifen.
https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancerdrugs/drugs/tamoxifen
Dean, L. (2019, May 1). Tamoxifen Therapy and CYP2D6 Genotype - Medical Genetics
Summaries – NCBI Bookshelf. NCBI. https://www.ncbi.nlm.nih.gov/books/NBK247013/
Goetz, M. P., Sangkuhl, K., Guchelaar, H.-J., Schwab, M., Province, M., Whirl-Carrillo, M.,
Symmans, W. F., McLeod, H. L., Ratain, M. J., Zembutsu, H., Gaedigk, A., van Schaik,
R. H., Ingle, J. N., Caudle, K. E., & Klein, T. E. (2018). Clinical Pharmacogenetics
Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.
Clinical Pharmacology & Therapeutics, 103(5), https://doi.org/10.1002/cpt.1007
Komen, S. G. (2020, May 29). Tamoxifen.
https://ww5.komen.org/BreastCancer/Tamoxifen.html
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Mayo Clinic. (2020, October 6). Tamoxifen (Oral Route). https://www.mayoclinic.org/drugssupplements/tamoxifen-oral-route/before-using/drg-20066208
National Cancer Institute. (2020, June 1). Hormone Therapy for Breast Cancer Fact Sheet.
https://www.cancer.gov/types/breast/breast-hormone-therapy-fact-sheet#r25
NSW Government, (2020, March). Fact Sheet 21: Pharmacogenetics/Phamacogenomic.
https://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-21pharmacogenomics-pharmacogenetics
U. S. National Library of Medicine (2020, September 28). Tamoxifen: MedlinePlus Drug
Information. https://medlineplus.gov/druginfo/meds/a682414.html
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