Breast cancer is the most frequently diagnosed type of cancer among women, both in developed and developing regions. The majority of patients is postmenopausal at diagnosis and has hormone... Show moreBreast cancer is the most frequently diagnosed type of cancer among women, both in developed and developing regions. The majority of patients is postmenopausal at diagnosis and has hormone sensitive tumours, implying that patients may benefit from endocrine therapy, both in curative and in metastatic setting. In the last twenty-five years, the treatment of patients with hormone-sensitive early breast cancer has largely changed as more treatment options became available, while over the last decade more tailored treatment was aimed at. This has resulted in an improved prognosis.2-4 Nevertheless, part of breast cancer patients will develop recurrent disease, especially late recurrences can occur in hormone sensitive disease while the various therapies may be associated with side effects which can affect quality of life. The research described in this thesis was designed to gain further insight in optimal treatment of early breast cancer patients, especially in postmenopausal women with hormone sensitive tumours. Show less
Water, W. van de; Fontein, D.B.Y.; Nes, J.G.H. van; Bartlett, J.M.S.; Hille, E.T.M.; Putter, H.; ... ; Velde, C.J.H. van de 2013
Background: In evaluating follow-up of early breast cancer, patients' views on care are important. The aim of this study was to evaluate the effect of the introduction of nurse practitioners (NPs)... Show moreBackground: In evaluating follow-up of early breast cancer, patients' views on care are important. The aim of this study was to evaluate the effect of the introduction of nurse practitioners (NPs) in a breast cancer unit on patients' informational needs, preferences and attitude towards follow-up. Patients and methods: A cross-sectional survey was performed among two groups in 2005. Group A (n = 89) consisted of patients operated before, and group B (n = 100) after the introduction of a breast cancer unit (respectively in 1998-1999 and 2001-2004). Results: Response was 72% in group A and 84% in group B. Median follow-up was 69 (54-86) and 33 (0-57) months, respectively. Aspects highly appreciated by patients in both groups were lifetime follow-up, information about prognosis, life style and additional investigations. Important discussion subjects were fatigue, pain, genetic factors, prevention and arm function/lymph-oedema. Less valued aspects were information about peers, conversations with psychologists or social workers, breast reconstruction, and acceptation by family members. The informational needs and preferences did not differ statistically significantly between both groups. In group B, communication with the caregiver was valued higher and more patients indicated that the caregiver took the time needed. More patients in group B indicated that follow-up could be performed by the NP. Duration of follow-up correlated with preferred frequency, not with informational needs in follow-up, only young age increased these needs. Conclusion: Despite the limitations of this retrospective study, we conclude that while expectations and informational needs did not change with the introduction of a NP to the standard care, patient satisfaction increased and communication and time taken were appreciated more. (C) 2011 Elsevier Ltd. All rights reserved. Show less
Epithelial mesenchymal transition (EMT) plays an important role in the development of metastases. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are... Show moreEpithelial mesenchymal transition (EMT) plays an important role in the development of metastases. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by transcription factors, such as SNAIL, SLUG, and TWIST. We examined the prognostic value of these factors as well as E-cadherin and N-cadherin, in a well-described large cohort of breast cancer patients treated with primary surgery. Analyses were stratified by estrogen receptor (ER) status, because of its crucial role in the regulation of these transcription factors. SNAIL, SLUG, and TWIST expression were examined on a TMA containing 575 breast tumors using immunohistochemistry. Nuclear expression was quantified using a weighted histoscore and classified as high versus low expression, based on the median histoscore. High expression of SNAIL, SLUG, and TWIST was seen in 54, 50, and 50% of tumors, respectively. The level of SNAIL (P = 0.014) and TWIST (P = 0.006) expression was associated with a worse patient relapse-free period, specifically in patients with ER-positive tumors (interaction Cox proportional hazards P = 0.039). Combining both factors resulted in an independent prognostic factor with high discriminative power (both low versus either high: HR 1.15; both low versus both high HR 1.84; P = 0.010). Co-expression of SNAIL-TWIST was associated with low-E-cadherin and high-N-cadherin expression, especially in ER-positive tumors (P = 0.009), suggesting that, through interactions with ER, SNAIL and TWIST may regulate E- and N-cadherin expression, thereby inducing EMT. Our results are indicative that SNAIL and TWIST play a crucial role in EMT through regulation of E- and N-cadherin expression, exclusively in ER-positive breast cancer patients. Show less
Stroma tissue surrounding cancer cells plays an important role in tumor development and behavior. In colorectal cancer, it has been found that the amount of stroma within the primary tumor is of... Show moreStroma tissue surrounding cancer cells plays an important role in tumor development and behavior. In colorectal cancer, it has been found that the amount of stroma within the primary tumor is of prognostic value. We therefore have evaluated the prognostic value of this tumor-stroma ratio for breast cancer. A cohort of 574 early breast cancer patients, primarily treated with surgery between 1985 and 1994 was analyzed for the tumor-stroma ratio. The percentage of stroma was visually estimated on Haematoxylin-Eosin (H&E) stained histological sections. Patients with more than 50% intra-tumor stroma were quantified as stroma rich and patients with less than 50% as stroma poor. For the total group of patients, stroma-rich tumors had a shorter relapse-free period (RFP) (P = 0.001) and overall survival (OS) (P = 0.025) compared to stroma-poor tumors. Tumor-stroma ratio was an independent prognostic parameter for the total group of patients (P < 0.001) and also in stratified analysis based on systemic treatment. Importantly, in the triple-negative cancer subpopulation, patients with stroma-rich tumors had a 2.92 times higher risk of relapse (P = 0.006) compared to those with stroma-poor tumors, independently of other clinico-pathological parameters. Five-year RFP-rates for triple-negative cancer patients with stroma-rich compared to stroma-poor tumors were 56 and 81%, respectively. Tumor-stroma ratio has proven to be an independent prognostic factor for RFP in breast cancer patients and especially in the triple-negative cancer subpopulation. Tumor-stroma ratio could be easily implemented in routine daily pathology diagnostics, as it is simple to determine, reproducible, and performed in quick time. Show less
In breast cancer, the prognostic impact of COX2 expression varies widely between studies. We examined the prognostic value of COX2 expression in a large cohort of breast cancer patients treated... Show moreIn breast cancer, the prognostic impact of COX2 expression varies widely between studies. We examined the prognostic value of COX2 expression in a large cohort of breast cancer patients treated with primary surgery between 1985 and 1994 and explained the variable results of COX2 expression found in the literature. A tissue microarray was constructed of available tumour material, and ER, PgR, HER2, Ki67 and COX2 were examined by immunohistochemistry. Median follow-up was 19 years. Fifty-five percent (n = 369/677) of patients received no systemic treatment. COX2 was scored using a weighted histoscore. Analysis of COX2 expression in two groups based on the median (148; below vs. above) showed an increased hazard ratio (HR) of 1.35 (95% CI 1.05-1.75, P = 0.021) for disease-free survival (DFS) and of 1.39 (95% CI 1.03-1.82, P = 0.016) for overall survival (OS). However, COX2 did not remain independent in multivariate analysis. In patients with hormone receptor positive tumours, COX2 expression had a negative influence on outcome (low vs. high: DFS: HR 1.37, 95% CI 1.07-1.76, P = 0.013). This effect disappeared when endocrine therapy was administered (low vs. high: DFS: HR 0.93, 95% CI 0.51-1.70, P = 0.811) while it remained statistically significant when endocrine therapy was omitted (low vs. high: DFS: HR 1.48, 95% CI 1.12-1.94, P = 0.005). Our results show that COX2 plays a role in hormonal pathways. Our results can explain the results found in previously published studies. Show less
PURPOSE: We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone... Show morePURPOSE: We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone health. METHODS: Patients received exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of treatment. Bone turnover markers were also measured. RESULTS: Patients receiving tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in lumbar spine BMD between treatment groups (P < 0.0001 at both time points). Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P < 0.05 at both time points). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane. CONCLUSIONS: Exemestane resulted in decreases in BMD and increases in bone turnover markers. BMD increased and bone turnover markers decreased with tamoxifen. Show less
Nonclassical HLAs, HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and... Show moreNonclassical HLAs, HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and related the results to tumor expression of classical HLA class I. Our study population (n = 677) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1995. Tissue microarray sections of arrayed tumor and normal control material were immunohisto-chemically stained for HLA-E and HLA-G. For evaluation of HLA-E and HLA-G and the combined variable, HLA-EG, a binary score was used. Expression of classical HLA class I molecules was determined previously. HLA-E, HLA-G, and HLA-EG on breast tumors were classified as expression in 50, 60, and 23% of patients, respectively. Remarkably, only in patients with loss of classical HLA class I tumor expression, expression of HLA-E (p = 0.027), HLA-G (p = 0.035), or HLA-EG (p = 0.001) resulted in a worse relapse-free period. An interaction was found between classical and nonclassical HLA class I expression (p = 0.002), suggestive for a biological connection. We have demonstrated that, next to expression of classical HLA class I, expression of HLA-E and HLA-G is an important factor in the prediction of outcome of breast cancer patients. These results provide further evidence that breast cancer is immunogenic, but also capable of evading tumor eradication by the host's immune system, by up-or downregulation of HLA class Ia and class Ib loci. The Journal of Immunology, 2010, 185: 7452-7459. Show less
Voskuil, D.W.; Nes, J.G.H. van; Junggeburt, J.M.C.; Velde, C.J.H. van de; Leeuwen, F.E. van; Haes, J.C.J.M. de 2010
Patients and methods: In this side study of a large clinical trial, lifestyle and quality-of-life questionnaires were filled out 1 and 2 years after the start of endocrine therapy (T1 and T2,... Show morePatients and methods: In this side study of a large clinical trial, lifestyle and quality-of-life questionnaires were filled out 1 and 2 years after the start of endocrine therapy (T1 and T2, respectively) and included a pre-diagnosis lifestyle assessment (T0). A total of 435 breast cancer patients returned both questionnaires. Results: Individuals with a physical activity level above the median who maintained this level from T0 to T1 reported the best global quality of life and physical functioning and the least fatigue at T2, as compared with individuals with low levels of physical activity which further decreased after diagnosis (difference of +16, +14, and -22 points on a 0-100 quality-of-life scale, respectively; P < 0.01). Overweight or obese women who gained body weight after diagnosis reported worst quality of life and most fatigue as compared with women who maintained a stable body weight (difference of -8, -10 and +2 points, respectively; P < 0.01). Conclusion: Maintaining high pre-diagnosis physical activity levels and a healthy body weight is associated with better quality of life after breast cancer. Show less
Aims: After treatment, early breast cancer patients undergo follow-up according to standard regimens. After the first year, the main goal is particularly to detect locoregional recurrences (LRR).... Show moreAims: After treatment, early breast cancer patients undergo follow-up according to standard regimens. After the first year, the main goal is particularly to detect locoregional recurrences (LRR). Our aim was to develop a simple prognostic index to predict LRR to tailor the follow-up programme. Methods: We used data from four large international clinical randomised trials and constructed the prognostic index using Cox proportional hazards regression. The bootstrap (a resampling method) was used for internal validation. Results: A total of 6516 patients treated according to current guidelines with complete covariable information were used for analysis. Covariables important for LRR in patients treated with breast conserving therapy were age, pathological tumour status, boost and surgical margins. The same variables were important for patients treated with a mastectomy, however, instead of the boost, the pathological nodal status was important. The index is composed to consist of three groups based on LRR risk after 10-years. Conclusions: We constructed a simple prognostic index that can be used to estimate risks of LRR in patients with early breast cancer. The prognostic index enables patients to be stratified into three subgroups with different outcomes with regard to LRR. (C) 2010 Elsevier Ltd. All rights reserved. Show less
AIMS After treatment, early breast cancer patients undergo follow-up according to standard regimens. After the first year, the main goal is particularly to detect locoregional recurrences (LRR).... Show moreAIMS After treatment, early breast cancer patients undergo follow-up according to standard regimens. After the first year, the main goal is particularly to detect locoregional recurrences (LRR). Our aim was to develop a simple prognostic index to predict LRR to tailor the follow-up programme. METHODS We used data from four large international clinical randomised trials and constructed the prognostic index using Cox proportional hazards regression. The bootstrap (a resampling method) was used for internal validation. RESULTS A total of 6516 patients treated according to current guidelines with complete covariable information were used for analysis. Covariables important for LRR in patients treated with breast conserving therapy were age, pathological tumour status, boost and surgical margins. The same variables were important for patients treated with a mastectomy, however, instead of the boost, the pathological nodal status was important. The index is composed to consist of three groups based on LRR risk after 10-years. CONCLUSIONS We constructed a simple prognostic index that can be used to estimate risks of LRR in patients with early breast cancer. The prognostic index enables patients to be stratified into three subgroups with different outcomes with regard to LRR. Show less
Methods: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. Results: From 2001 to January 2006, 2754 Dutch patients were... Show moreMethods: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. Results: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < 2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). Discussion: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement. Show less
