The role of pharmacogenomics in personalising the use of tamoxifen in breast cancer

Autor: Johnston, Simon J., Li-Chia Chen, Kwok-Leung Cheung
Přispěvatelé: de Mello, RA
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Johnston, S J, Chen, L-C & Cheung, K-L 2013, The role of pharmacogenomics in personalising the use of tamoxifen in breast cancer . in RA de Mello (ed.), Tamoxifen, Concepts and Cancer : New Paradigms ., Chapter IX, Nova Science Publishers, New York, pp. 135-46 .
University of Manchester-PURE
Popis: Tamoxifen is a well-established endocrine therapy used in the treatment of hormonereceptor positive breast cancer. In recent years, its role in adjuvant and advanced breast cancer settings has been superseded by aromatase inhibitors. The prodrug tamoxifen is metabolised in the liver into several primary and secondary metabolites via cytochrome P450 enzymes. The main active forms are endoxifen and 4-hydroxytamoxifen, with CYP2D6 being a key enzyme in the production of both. There is evidence that tamoxifen-associated hot flushes are an indicator of clinical efficacy of tamoxifen. Co-prescription of CYP2D6 inhibitors, including selective serotonin re-uptake inhibitors (SSRIs) commonly used to treat hot flushes, may decrease the clinical efficacy of tamoxifen and should be used with caution. Moreover, there is evidence that patients with poor CYP2D6-mediated tamoxifen metaboliser phenotype ave worse clinical outcomes, and fewer hot flushes, than those with other phenotypes. Further research is necessary to clarify whether extensive metabolisers have the best clinical outcomes on tamoxifen. Preliminary data suggest that in individuals of certain CYP2D6 phenotype, amoxifen may have equivalent efficacy, and be considered as an alternative to aromatase inhibitors if there were concerns over the side effect profile and cost of the latter. Thus the role of tamoxifen may be redefined in a new era of personalised breast cancer treatment. The role of pharmacogenomics in personalising the use of tamoxifen in breast cancer (PDF Download Available). Available from: https://www.researchgate.net/publication/236231150_The_role_of_pharmacogenomics_in_personalising_the_use_of_tamoxifen_in_breast_cancer [accessed Mar 31, 2017].
Databáze: OpenAIRE