Tamoxifen Pharmacogenetics and Clinical Effects

The purpose of this research is to try to identify which women who take tamoxifen are likely to suffer from hot flashes or are more likely to have other side effects or benefits from the drug. The researchers will do so by determining whether there are mutations that normally occur in human DNA that might influence the way individuals respond to medications.

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

1. 18-years or older
2. Women with a prior breast cancer or who are at a high risk for developing the disease and about to start tamoxifen therapy.
3. Participants must not be treated with concomitant chemotherapy or hormone therapy other than tamoxifen. They must not have ovarian ablation or currently being treated with radiation therapy and/or chronic corticosteroids.
4. The participant must not be taking anti-hot flash therapy (clonidine, bellergal, megestrol acetate). Vitamin E, selective serotonin reuptake inhibitors, or herbal remedies are allowed provided that the participant has been taking the remedy for at least 4 weeks and intends to continue the remedy for at least the first month while on the study, and allows for one-month follow up evaluation (hot flash diaries and blood samples).
5. The participant must not be pregnant or lactating.
6. The participant is able and willing to sign an informed consent.

• RESULTRae JM, Goetz MP, Hayes DF, Ingle JN, Li L, Storniolo AM, Stearns V, Flockhart DA. CYP2D6 genotype and tamoxifen response. Breast Cancer Res. 2005 Jul 29;7(5):E6. doi: 10.1186/bcr1297. No abstract available. PMID 16168100
• RESULTLim YC, Desta Z, Flockhart DA, Skaar TC. Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother Pharmacol. 2005 May;55(5):471-8. doi: 10.1007/s00280-004-0926-7. Epub 2005 Feb 1. PMID 15685451
• RESULTJin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9. doi: 10.1093/jnci/dji005. PMID 15632378
• RESULTStearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst. 2003 Dec 3;95(23):1758-64. doi: 10.1093/jnci/djg108. PMID 14652237
• RESULTLee KH, Ward BA, Desta Z, Flockhart DA, Jones DR. Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trial. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):245-53. doi: 10.1016/s1570-0232(03)00218-6. PMID 12798184
• DERIVEDHayes DF, Skaar TC, Rae JM, Henry NL, Nguyen AT, Stearns V, Li L, Philips S, Desta Z, Flockhart DA; Consortium on Breast Cancer Pharmacogenomics (COBRA). Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results. Clin Pharmacol Ther. 2010 Nov;88(5):626-9. doi: 10.1038/clpt.2010.143. Epub 2010 Sep 8.