Tamoxifen-associated hot flash severity is inversely correlated with endoxifen concentration and CYP3A422

Tamoxifen use is often limited in some patients due to adverse effects including severe hot flash symptoms. Tamoxifen undergoes hepatic bioactivation by CYP2D6 and CYP3A4 to form the active metabolite endoxifen. It remains unclear whether the extent of attained endoxifen level or genetic polymorphis...

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Bibliographic Details
Published in:Breast cancer research and treatment 2014-06, Vol.145 (2), p.419-428
Main Authors: Baxter, Simon D., Teft, Wendy A., Choi, Yun-Hee, Winquist, Eric, Kim, Richard B.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Hormonal - adverse effects
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Cancer research
Cancer therapies
Clinical Trial
Clinical trials
Cytochrome P-450
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P-450 CYP3A - genetics
Female
Genetic polymorphisms
Genotype & phenotype
Health aspects
Hot Flashes - chemically induced
Hot Flashes - genetics
Humans
Medicine
Medicine & Public Health
Menopause
Metabolites
Middle Aged
Oncology
Pharmacogenetics
Pharmacology
Self Report
Side effects
Surveys
Tamoxifen
Tamoxifen - adverse effects
Tamoxifen - analogs & derivatives
Tamoxifen - blood
Women
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Summary:Tamoxifen use is often limited in some patients due to adverse effects including severe hot flash symptoms. Tamoxifen undergoes hepatic bioactivation by CYP2D6 and CYP3A4 to form the active metabolite endoxifen. It remains unclear whether the extent of attained endoxifen level or genetic polymorphisms in drug metabolizing enzymes is associated with the frequency and severity of hot flashes. We conducted a prospective study using self-reported surveys to assess tamoxifen side effects experienced during the week prior to clinic visits of 132 female breast cancer patients on tamoxifen therapy, and hot flash severity scores were tabulated. At the time of clinic visit, blood samples were obtained to determine tamoxifen and its metabolite levels and to determine CYP2D6 and CYP3A4 genotypes. The majority of participants (77 %) experienced hot flashes, with 11 % experiencing severe or very severe symptoms. We observed an inverse correlation between endoxifen concentration and hot flash severity score following adjustment for age, BMI, and menopausal status in patients with non-zero scores ( p  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-014-2963-1