Hot flashes are not predictive for serum concentrations of tamoxifen and its metabolites

BMC Cancer

Nynke GL Jager⁷  Rutger HT Koornstra³  Andrew D Vincent⁴  Ron HN van Schaik⁵  Alwin DR Huitema⁷  Tiny M Korse⁶  Jan HM Schellens²  Sabine C Linn¹  Jos H Beijnen² 

[1] Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

[2] Department of Pharmaceutical Sciences, Faculty of Science, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, 3508 TB Utrecht, The Netherlands

[3] Department of Molecular Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

[4] Department of Biometrics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

[5] Department of Clinical Chemistry, Erasmus University Medical Centre, ‘s Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands

[6] Department of Clinical Chemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

[7] Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands

关键词: Breast cancer;    CYP2D6;    Estrogen levels;    Hot flashes;    Tamoxifen;    Endoxifen;   

Others  :  859180
DOI  :  10.1186/1471-2407-13-612

 received in 2013-03-06, accepted in 2013-12-16,  发布年份 2013

【 摘 要 】

Background

Tamoxifen has dramatically reduced the recurrence and mortality rate of estrogen receptor positive breast cancer. However, the efficacy of tamoxifen varies between individuals and 40% of patients will have a recurrence despite adjuvant tamoxifen treatment. Factors that predict tamoxifen efficacy would be helpful for optimizing treatment. Serum concentrations of the active metabolite, endoxifen, may be positively related to treatment outcome. In addition, hot flashes are suggested to be positively associated with tamoxifen treatment outcome.

Methods

We investigated in a series of 109 patients whether the frequency and severity of hot flashes were related to concentrations of tamoxifen and its metabolites. A serum sample of all patients was analyzed for the concentration of tamoxifen, N-desmethyltamoxifen, endoxifen and 4-hydroxytamoxifen, as well as for estradiol concentrations and several single nucleotide polymorphisms in CYP2D6. Additionally, these patients completed a questionnaire concerning biometric data and treatment side effects.

Results

We found no evidence supporting an association between concentrations of tamoxifen or metabolites and either the frequency or severity of hot flashes in the covariate unadjusted analyses. However, including interactions with menopausal status and pre-treatment hot flash (PTHF) history indicated that post-menopausal women with PTHF experienced an increasing frequency of hot flashes with increasing serum concentrations of tamoxifen and its metabolites. This finding was not altered when adjusting for potential confounding factors (duration of tamoxifen treatment, CYP2D6 phenotype, estradiol serum concentration, age and body mass index). In addition we observed a positive association between body mass index and both hot flash frequency (p = 0.04) and severity (p < 0.0001). We also observed that patients with lower estradiol levels reported more severe hot flashes (p = 0.02).

Conclusions

No univariate associations were observed between concentrations of active tamoxifen metabolites and either the frequency or severity of hot flashes during treatment. However, the frequency of hot flashes may be exacerbated by higher serum concentrations of tamoxifen and its metabolites in post-menopausal women with a history of hot flashes prior to tamoxifen treatment.

【 授权许可】

   
2013 Jager et al.; licensee BioMed Central Ltd.

【 图 表 】

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