Breast cancer is the most common malignancy and the leading cause of cancer related death in women of the western world. For most women, increasing age is the primary risk factor for breast... Show more Breast cancer is the most common malignancy and the leading cause of cancer related death in women of the western world. For most women, increasing age is the primary risk factor for breast cancer. Therefore, the number of breast cancer patients is expected to further increase in the coming years. The work presented in this thesis is part of the collaborative FOCUS project, seeking insight into breast cancer disease (in the elderly), aiming to define normal tissue, breast cancer, and therapeutic sensitivity differences in observational, population-based cohorts consisting of elderly breast cancer patients. Topics discussed in this thesis are differences and clinical value of molecular differentiation, immune evasion, proliferative and apoptotic signaling; but also the predictive value of IGF1R and HER2 expression on the breast tumors. Last but not least, we discuss the effects of aging on tumorgenesis and the road to precision medicine. Only when all medical specialties bound to the care and cure of older cancer patients join forces, known as a multidisciplinary oncogeriatric battlefront, treatment goals, and implementation hereof will be achieved. Show less
Engels, C.C.; Kiderlen, M.; Bastiaannet, E.; Eijk, R. van; Mooyaart, A.; Smit, V.T.H.B.M.; ... ; Liefers, G.J. 2016
Selection of patients who will likely respond or will develop relevant side effects has the potential to improve anticancer therapy. Considering the many contributing factors in drug disposition,... Show moreSelection of patients who will likely respond or will develop relevant side effects has the potential to improve anticancer therapy. Considering the many contributing factors in drug disposition, we hypothesized that variability in drug disposition could be better explained by phenotype, rather than by the genotype alone. In this thesis, phenotype tests in oncology were studied, with a focus on phenotype breath tests and CYP2D6 metabolism in breast cancer patients using tamoxifen. A review is given of phenotype studies published before 2011 addressing drug metabolizing enzymes in relation to anticancer drugs. The 13C-dextromethorphan-breath test was related to CYP2D6 genotype and serum concentrations of endoxifen, the active metabolite of tamoxifen. A 13C-dextromethorphan breath test was equally predictive of endoxifen levels as compared to the CYP2D6 genotype. We showed that there was no difference in CYP2D6 phenotype between metastasized patients and early breast cancer patients. Because endoxifen levels did not significantly differ between the two groups as well, our findings do not have clinical implications thus far. Show less
This thesis was divided in two parts. Part I demonstrated benefit of zoledronic acid addition to chemotherapy in terms of pathological response in postmenopausal women. Part II is all about... Show moreThis thesis was divided in two parts. Part I demonstrated benefit of zoledronic acid addition to chemotherapy in terms of pathological response in postmenopausal women. Part II is all about neoadjuvant endocrine therapy, and discusses the optimal duration of this treatment and the information on treatment efficacy that aromatase-inhibitor specific adverse events may provide. Show less
Kaptein, A.A.; Schoones, J.W.; Fischer, M.J.; Thong, M.S.Y.; Kroep, J.R.; Hoeven, K.J.M. van der 2015
Women with breast cancer respond to the illness and its medical management in their own personal way. Their coping behavior and self-management are determined by their views (cognitions) and... Show moreWomen with breast cancer respond to the illness and its medical management in their own personal way. Their coping behavior and self-management are determined by their views (cognitions) and feelings (emotions) about symptoms and illness: their illness perceptions. This paper reports the results of a systematic literature review of illness perceptions and breast cancer. In the 12 studies identified, published between 2012 and 2015, illness perceptions were found to be important concomitants of medical and behavioral outcomes: fear of recurrence, distress, quality of life, satisfaction with medical care, use of traditional healers, and risk perception. Intervention studies are called for where the effects are examined of replacing unhelpful illness perceptions by more constructive ones. Health care providers do well by incorporating illness perceptions in their care for women with breast cancer, as this is instrumental in improving patients' quality of life. Show less
Kiderlen, M.; Ponti, A.; Tomatis, M.; Boelens, P.G.; Bastiaannet, E.; Wilson, R.; ... ; EusomaDB Working Grp 2015
There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin... Show moreThere is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the human body the injected insulin glargine is rapidly degraded into two main metabolites with a metabolic activity. These two compounds have a mitogenic potential that was not increased compared to regular insulin. Gene expression analysis on a stimulated MCF7-based cell line panel showed that the insulin-like growth factor 1 (IGF1) receptor was the main receptor involved in the insulin analogue induced mitogenic signaling. A chronic exposure experiment with the humanized p53R270H+/-WAPCre mouse model revealed that none of the commercially available insulin analogues induced mammary gland tumor multiplicity or decreased the tumor latency time. However, a follow-up whole transcriptome analysis indicated that some tumors in the insulin glargine treatment group had a higher Warburg potential. Altogether, these results suggest that insulin glargine exposure was not involved in tumor initiation but it might have affected tumor progression. Show less
Preclinical and clinical studies reveal that left-sided breast cancer radiotherapy is associated with an increased rate of major coronary events. Consequently, when irradiating women with left... Show morePreclinical and clinical studies reveal that left-sided breast cancer radiotherapy is associated with an increased rate of major coronary events. Consequently, when irradiating women with left-sided breast cancer, specific measures should be taken to decrease the heart dose as much as possible and to avoid radiation-induced coronary artery disease. This thesis focuses on several strategies to optimise the radiation treatment for patients with left-sided breast cancer. With respect to whole breast irradiation we concluded that: __ the routine use of MR images in addition to the CT scan, when delineating either the glandular breast tissue or the lumpectomy cavity, does not have added value. __ tangential IMRT technique combined with a breath-hold technique should be the treatment technique of choice for left-sided breast cancer. __ a breath-hold technique should and can be used in all left-sided breast cancer patients, regardless of age and breast size. __ breath-hold in left-sided whole breast radiotherapy results in a less pronounced increase of coronary calcium score and, hence, could result in less radiation-induced cardio vascular damage. Show less
