This thesis describes the preferences of both older patients with breast cancer and clinicians to optimize the current care of this patient group. The significant increase in the number of breast... Show moreThis thesis describes the preferences of both older patients with breast cancer and clinicians to optimize the current care of this patient group. The significant increase in the number of breast cancer patients above the age of 65 years necessitates insight into their preferences. Decision-making regarding treatment of early breast cancer is often difficult as decisions need to be made between two surgical options and about the addition of systemic therapy. Like younger patients, older patients are faced with these difficult decisions (together with their clinician). However, treatments for early breast cancer differ substantially between younger and older patients, which possibly can be explained by the preferences of older patients or their clinicians. Currently, little is known about the preferences of older patients, while this knowledge is particularly of great value. To assess how the current care of older patients and the treatment-decision-making process with this patient group can be optimised, we explore the preferences and motivations of older patients with early breast cancer; if and how their preferences for treatment and participation in decision-making differ from those of younger patients; and the treatment preferences of breast cancer specialists with regard to treatment of older patients. Show less
Rossum, A.G.J. van; Kok, M.; Werkhoven, E. van; Opdam, M.; Mandjes, I.A.M.; Leeuwen-Stok, A.E. van; ... ; MATADOR Trialists' Grp 2018
In this thesis we reflect on the effects differential DNA binding of the estrogen receptor α (ERα) can have on the behavior of breast cancer and which factors can contribute to this. ERα is a... Show moreIn this thesis we reflect on the effects differential DNA binding of the estrogen receptor α (ERα) can have on the behavior of breast cancer and which factors can contribute to this. ERα is a transcription factor than can drive tumor cell proliferation and approximately 70% off all breast tumors is thought to be dependent on the activity of this hormone-mediated transcription factor. After stimulation of ERα a wild variety of co-factors are recruited, leading to the assembly of a transcriptional complex. Although there are multiple ways of targeting the action of ERα and thereby inhibiting tumor growth, still a significant proportion of patients develop a recurrence. Cross-resistance between the different endocrine therapy options can occur, but a proportion of patients that relapse on one type of therapy can still benefit from a different treatment modality, illustrating the existence of multiple resistance mechanisms which can be treatment selective. A better understanding of ERα-biology and the development of endocrine therapy resistance, can lead the way to the discovery of novel biomarkers and potential drug targets, that can further increase patient survival. Show less
Hoekstra, N.; Fleury, E.; Lara, T.R.M.; Baan, P. van der; Bahnerth, A.; Struik, G.; ... ; Pignol, J.P. 2018
Introduction: For early stage breast cancer patients, non-breast cancer mortality including secondary cancers and cardiac events can overshadow the benefit of adjuvant radiotherapy. This study... Show moreIntroduction: For early stage breast cancer patients, non-breast cancer mortality including secondary cancers and cardiac events can overshadow the benefit of adjuvant radiotherapy. This study evaluates the excess risk of secondary cancer for various breast radiotherapy techniques including accelerated partial breast irradiation (APBI).Methods: Secondary cancers Lifetime Attributable Risks (LAR) were calculated using a modified BEIR-VII formalism to account for the specific survival of breast cancer patients. Those survivals were extracted from the SEER database. Doses scattered to various organs were measured into a Rando phantom with custom-made breast phantoms. Treatments delivered typical doses of brachytherapy APBI (34 Gy in 10 fractions), external beam APBI (38.5 Gy in 10 fractions) using 3D-conformal, Cyberknife stereotactic (CK), or VMAT, as well as whole breast irradiation (WBI) delivering 42.5 Gy in 16 fractions.Results: WBI resulted in the highest total LAR, with 4.3% excess risk of secondary cancer for a patient treated at age 50 years. Lung cancers accounted for 75-97% of secondary malignancies. For a typical early stage patient irradiated at 50, the excess risks of secondary lung cancer were 1.1% for multicatheter HDR, between 2.2% and 2.5% for 3D-CRT or CK, 3.5% for VMAT APBI, and 3.8% for WBI.Conclusions: APBI reduces the risk of secondary cancer 2-4 fold compared to WBI. These techniques are well suited for long-living early stage breast cancer patients. HDR brachytherapy and 3D-conformal APBI achieve mean lung doses between 1 and 1.5 Gy, which could serve as reference. (C) 2018 Elsevier B.V. All rights reserved. Show less
As a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are... Show moreAs a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are not representative for the older population. In this thesis, we investigated whether there is variation in treatment and survival among older women with breast cancer in five European countries. Moreover, we study the long term efficacy of two types of adjuvant endocrine therapy in postmenopausal women. In addition, the effect of age and comorbidities on breast cancer death in the presence of competing mortality is studied. Finally, we investigate whether other endpoints in clinical studies might be more relevant for the older population and we introduce a new endpoint for clinical research in the older population with cancer. Show less
Blok, E.J.; Kroep, J.R.; Kranenbarg, E.M.K.; Duijm-De Carpentier, M.; Putter, H.; Liefers, G.J.; ... ; TEAM Study Group 2018
Although the survival of breast cancer has improved the past decades, there is still major over- and undertreatment for the majority of patients. The aim of this research was to identity the most... Show moreAlthough the survival of breast cancer has improved the past decades, there is still major over- and undertreatment for the majority of patients. The aim of this research was to identity the most optimal adjuvant endocrine therapy, with regard to the optimal duration of therapy and the selection of subgroups who require selected therapy. Show less
The insulin receptor (INSR) and the insulin growth factor 1 receptor (IGF1R) play important roles in the etiology of both diabetes mellitus and breast cancer. We aimed to evaluate the expression of... Show moreThe insulin receptor (INSR) and the insulin growth factor 1 receptor (IGF1R) play important roles in the etiology of both diabetes mellitus and breast cancer. We aimed to evaluate the expression of hormone and insulin-related proteins within or related to the PI3K and MAPK pathway in breast tumors of women with or without diabetes mellitus, treated with or without insulin (analogues).\nImmunohistochemistry was performed on tumor tissue of 312 women with invasive breast cancer, with or without pre-existing diabetes mellitus, diagnosed in 2000-2010, who were randomly selected from a Danish breast cancer cohort. Women with diabetes were 2:1 frequency matched by year of birth and age at breast cancer diagnosis to those without diabetes. Tumor Microarrays were successfully stained for p-ER, EGFR, p-ERK1/2, p-mTOR, and IGF1R, and scored by a breast pathologist. Associations of expression of these proteins with diabetes, insulin treatment (human insulin and insulin analogues) and other diabetes medication were evaluated by multivariable logistic regression adjusting for menopause and BMI; effect modification by menopausal status, BMI, and ER status was assessed using interactions terms.\nWe found no significant differences in expression of any of the proteins in breast tumors of women with (n = 211) and without diabetes (n = 101). Among women with diabetes, insulin use (n = 53) was significantly associated with higher tumor protein expression of IGF1R (OR = 2.36; 95%CI:1.02-5.52; p = 0.04) and p-mTOR (OR = 2.35; 95%CI:1.13-4.88; p = 0.02), especially among women treated with insulin analogues. Menopause seemed to modified the association between insulin and IGF1R expression (p = 0.07); the difference in IGF1R expression was only observed in tumors of premenopausal women (OR = 5.10; 95%CI:1.36-19.14; p = 0.02). We found no associations between other types of diabetes medication, such as metformin, and protein expression of the five proteins evaluated.\nIn our study, breast tumors of women with pre-existing diabetes did not show an altered expression of selected PI3K/MAPK pathway-related proteins. We observed an association between insulin treatment and increased p-mTOR and IGF1R expression of breast tumors, especially in premenopausal women. This observation, if confirmed, might be clinically relevant since the use of IGF1R and mTOR inhibitors are currently investigated in clinical trials. Show less
Lam, S.W.; Noort, V. van der; Straaten, T. van der; Honkoop, A.H.; Peters, G.J.; Guchelaar, H.J.; E. boven 2018
Older women with breast cancer are underrepresented in the available evidence. Therefore, there is no solid evidence on how to treat older women with breast cancer. This thesis has three main... Show moreOlder women with breast cancer are underrepresented in the available evidence. Therefore, there is no solid evidence on how to treat older women with breast cancer. This thesis has three main conclusions: 1. There are large international differences in the treatment strategy of breast cancer among older women. These differences are not associated with a significant difference in prognosis. 2. The presence of comorbidity has an important impact on the general prognosis of older women with breast cancer. We did not show an important association between specific comorbidities or the use of co-medications and the breast cancer specific prognosis. 3. Concerning older women with breast cancer for research, there are very important methodological issues to take into account, including to avoidance of selection bias and the proper methodologies to take in to account the chance of dying from another cause of cancer: the competing risk of mortality. Future research should be done to create a tool which can assist in identifying the individualised treatment strategy for each older woman with breast cancer. This will have to take into consideration patient’s and tumour’s information, as well as the endpoints for each individual patient. Show less
Blok, E.J.; Bastiaannet, E.; Hout, W.B. van den; Liefers, G.J.; Smit, V.T.H.B.M.; Kroep, J.R.; Velde, C.J.H. van de 2018
