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Cancer Chemother Pharmacol (2014) 73:475484
DOI 10.1007/s00280-013-2346-z
ORIGINAL ARTICLE
Extraction of tamoxifen and its metabolites from formalinxed, parafnembedded tissues: an innovative quantitation method using liquid chromatography and tandem mass spectrometry
Ella S. M. Ng S. Bill Kangarloo Mie Konno Alexander Paterson Anthony M. Magliocco
Received: 28 March 2013 / Accepted: 31 October 2013 / Published online: 12 January 2014 The Author(s) 2014. This article is published with open access at Springerlink.com
signicantly lower in patients with recurrent cancer, suggesting that inter-individual variability in tamoxifen metabolism might partly account for the development of cancer recurrence. Nevertheless, other causes such as non-compliance or stopping therapy of tamoxifen could possibly lead to the concentration differences.
Conclusions The ability to successfully study tamoxifen metabolism in such tissue samples will rapidly increase our knowledge of how tamoxifens action, metabolism and tissue distribution contribute to breast cancer control. However, larger population studies are required to understand the underlying mechanism of tamoxifen metabolism for optimization of its treatment.
Keywords Tamoxifen therapy Breast cancer recurrence Retrospective analysis Formalin-xed parafn-embedded tissue Tandem mass spectrometry
Introduction
Tamoxifen (TAM) has an important role in breast cancer treatment and prevention. This drug inhibits breast cancer by competing with endogenous estrogens for binding to estrogen receptors (ERs) in tumor tissue. Despite the proven anti-cancer effects of TAM, numerous studies have shown that the properties of this drug may cause detrimental effects such as increased risk of endometrial cancer and thromboembolic diseases [14]. Moreover, many patients develop resistance to TAM therapy after several years of treatment and eventually experience cancer recurrence [57]. The therapeutic and adverse effects of TAM have stimulated interest in understanding the biological activity of this drug. Indeed, there is a growing body of evidence indicating that the anti-proliferative
Abstract
Purpose Tamoxifen is a key therapeutic option for breast cancer treatment. Understanding its complex metabolism and pharmacokinetics is important for dose optimization. We examined the possibility of utilizing archival formalinxed parafn-embedded (FFPE) tissue as an alternative sample source for quantication since well-annotated retrospective samples were always limited.
Methods Six 15 m sections of FFPE tissues were deparafnized with xylene and puried using solid-phase extraction. Tamoxifen and its metabolites were separated and detected by liquid chromatographytandem mass spec-trometry using multiple-reaction monitoring.
Results This method was linear between...