Not all hormone receptor positive breast cancer patients benefit from tamoxifen treatment, but may be nonetheless exposed to its side effects (e.g. hot flashes). Tamoxifen needs bioactivation by... Show moreNot all hormone receptor positive breast cancer patients benefit from tamoxifen treatment, but may be nonetheless exposed to its side effects (e.g. hot flashes). Tamoxifen needs bioactivation by formation of the metabolite endoxifen, which is mainly catalyzed by the enzyme CYP2D6. In this thesis, we studied the variation in tamoxifen metabolism in relation to endoxifen serum concentration, tamoxifen efficacy and side effects, focusing on CYP2D6 activity and pharmacogenetics. The importance of good methodology for genotyping and endoxifen measurement was exemplified. In a large trial population, no association between CYP2D6 genotype and disease free survival or the occurence of hot flashes was found, although polymorphisms in the estrogen receptor-1 and UGT2B15 might be related to clinical outcome. Adherence, but not the concomitant use of CYP2D6 inhibiting medication was associated with breast cancer recurrence. CYP2D6 genotype and endoxifen-guided tamoxifen dose escalation led to an increase in endoxifen serum levels and a new 13C-Dextromethorphan breath test was used for phenotyping CYP2D6, which correlated well with CYP2D6 genotype and endoxifen levels. Finally, the CYP2D6 phenotype and endoxifen serum levels are currently prospectively related to breast cancer recurrence. This may lead to therapeutic drug monitoring and selection of patients who benefit most from tamoxifen. Show less
Heijer, M. den; Asperen, C.J. van; Harris, H.; Nippert, I.; Schmidtke, J.; Bouhnik, A.D.; ... ; Tibben, A. 2013
The primary aim of this thesis is to gain insight into which search facilities for spontaneously published stories facilitate breast cancer patients in finding stories by other patients in a... Show moreThe primary aim of this thesis is to gain insight into which search facilities for spontaneously published stories facilitate breast cancer patients in finding stories by other patients in a similar situation. According to the narrative approach, social comparison theory, and social cognitive theory, reading stories about similar others may have the most positive impact. The research followed a user-centred design: users of search facilities (i.e., patients who want to read stories written by others) were involved in every phase of the research so that the search facilities could be tailored to these users__ needs and preferences instead of forcing users to change their search behaviour to conform to search facilities that were developed without their involvement. We examined which breast cancer patients spontaneously publish their story online and which themes they write about in their stories, and how these stories are presented and disclosed on websites. We then examined which topics and writer characteristics patients prefer to search for and translated these preferences into search facilities. Finally, we examined which search facilities show the most positive effects on patient satisfaction and search success, and how patients actually search for stories written by others. The research was conducted from a clinical informatics perspective, using knowledge from the fields of information retrieval, human-computer interaction and psychology. Show less
Hezewijk, M. van; Bastiaannet, E.; Putter, H.; Scholten, A.N.; Liefers, G.J.; Rea, D.; ... ; Velde, C.J.H. van de 2013
