Abstract 3351: Assessment of tamoxifen drug compliance by serum metabolite profiling in premenopausal breast cancer patients.
Authors: Schroth Werner , Muerdter Thomas , Ganchev Boian , Saladores Pilar , Eccles Bryony , Lo Wing-Yee , Precht Jana C. , Schwab Matthias , Potter Kathy , Eccles Diana M. , Brauch Hiltrud B. 
Published: August 2014

Non-adherence to cancer drug therapy is a largely uncontrolled factor affecting clinical success. Long-term endocrine treatment of hormone-receptor positive breast cancer by tamoxifen is prone to premature stop of medication especially in young women due to severe side-effects commonly including hot flushes, fatigue, joint pain and nausea. Because non-adherence to prescribed therapy may mask any prognostic value of biomarkers for determining outcome, it is important to assess adherence both in prospective and retrospective studies that investigate pharmacogenetic associations. Currently, the estimation of compliance rates relies on prescription records and questionnaires that can be biased. We therefore determined actual rates of tamoxifen adherence from blood drug levels of the parent drug and its metabolites in 113 patients. All patients had adjuvant tamoxifen and were study subjects of the Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH), a study that explores the effect of genetic factors on breast cancer prognosis in young women (Eccles et al BMC Cancer 2007). We used LC-MS/MS analytics to quantify levels of tamoxifen and its clinically active (antiestrogenic) metabolites (Z)-endoxifen and (Z)-4-OH tamoxifen, as well as N-desmethyl tamoxifen, didesmethyl tamoxifen and 15 other metabolites. Among 113 patients, 9 (8%) patients had no quantifiable tamoxifen metabolites and were considered non-compliant. There was a higher proportion of patients with breast cancer recurrence or death in non-compliant (7 out of 9, 78%) compared to compliant patients (54 out of 104, 52%), although this correlation was not significant. Moreover, a higher proportion of non-compliant patients were prescribed GnRH agonists (4 out of 9, 44%) compared to compliant patients (21 out of 104, 20%), although not significant.

This study for the first time used serum metabolite profiling for the direct assessment of tamoxifen compliance of young women with breast cancer. We are currently pursuing this in a larger number of cases to better understand the confounding effects of non-compliance on outcome of genotype-phenotype associations. This is an important consideration for tamoxifen pharmacogenetic studies of young patients with a high risk for non-compliance. The pattern of irregular use and time-to-premature stop will be further investigated.

WS and TM contributed equally

Citation Format: Werner Schroth, Thomas Muerdter, Boian Ganchev, Pilar Saladores, Bryony Eccles, Wing-Yee Lo, Jana C. Precht, Matthias Schwab, Kathy Potter, Diana M. Eccles, Hiltrud B. Brauch. Assessment of tamoxifen drug compliance by serum metabolite profiling in premenopausal breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3351. doi:10.1158/1538-7445.AM2013-3351