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Background Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. Methods In the VOICE community—a European healthcare centre cluster intending to address VBHC from theory to practice—information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. Results Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. Conclusions To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions. [ABSTRACT FROM AUTHOR]

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Over the last 20 years, treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer has considerably improved. The development and addition of (neo)adjuvant trastuzumab to chemotherapy in patients with early HER2+ breast cancer (EHBC) has been shown to provide improvements in both disease-free survival (DFS) and overall survival, with some patients having a good prognosis being candidates for chemotherapy de-escalation strategies. However, despite such promising clinical outcomes, a significant proportion of patients still recur calling for the development of new preventive approaches. To this aim, the use of (neo)adjuvant trastuzumab for longer than one year or followed by lapatinib were tested without additional clinical improvement. Based on more recent advances, therapeutic strategies for patients with HER2+ tumours are now incorporating the use of newer (neo)adjuvant treatments, such as pertuzumab and trastuzumab emtansine, which have shown to further improve the invasive DFS (iDFS) benefit gained with trastuzumab. In this context, the tyrosine kinase inhibitor neratinib is approved in Europe for the extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2+ breast cancer who completed adjuvant trastuzumab-based therapy less than one year ago. Clinical data have demonstrated that neratinib significantly improves iDFS when used for the total recommended duration of 12 months. This review paper provides an overview of the treatment of patients with EHBC, with a focus on the post-trastuzumab use of neratinib. [ABSTRACT FROM AUTHOR]

Background: The substantial increase in the complexity of breast cancer care in the last few decades has resulted in significant improvements in survival rates and also in the quality of life of breast cancer survivors. However, across Europe there are variations in outcomes and access to the latest techniques. Whilst much of this variance is due to differences in health economies between European member states, training variation may also play a part. Training in breast cancer surgery varies greatly across Europe, not only in its basal discipline (general surgery, gynaecology or plastic surgery) but also in the length of training and whether there is any requirement for specialist training. Several countries have been leading the way in training breast specialist surgeons (the USA, the UK, Australia and New Zealand) with dedicated 1- or 2-year fellowships either within or in addition to standard training. Access to such training is limited and consequently many women in Europe are still treated by generalists, potentially denying them access to the best care. This paper reviews the issues surrounding training provision in breast surgery and some of the challenges which need to be addressed to improve the current situation. Summary: Breast surgery training in Europe is of variable quality and duration, which may result in variations in the quality of care received by patients with breast cancer. Specialist training standards are urgently required which should be adopted by all European member states. Excellent models are available in the USA, the UK and Australia and New Zealand on which to base this training. Key Messages: The quality of training in breast surgery needs to be upgraded and harmonised across Europe. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), breast cancer (BC) and prostate cancer (PC) continue to be high in the research and innovation agenda of the European Commission (EC). This is due to their exceptionally large burden to the national health systems, the profound economic effects of opportunity costs attributable to decreased working ability, premature mortality and the ever-increasing demand for both hospital and home-based medical care. Over the last two decades, the EC has been steadily increasing both the number of proposals being funded and the amounts of financial resources being allocated to these fields of research. This trend has continued throughout four consecutive science funding cycles, namely framework programme (FP)5, FP6, FP7 and Horizon 2020 (H2020). We performed a retrospective assessment of the outputs and outcomes of EC funding in AD, BC and PC research over the 1999–2019 period by means of selected indicators. These indicators were assessed for their ability to screen the past, present and future for an array of causal relationships and long-term trends in clinical, epidemiological and public health sphere, while considering also the broader socioeconomic impact of funded research on the society at large. This analysis shows that public–private partnerships with large industry and university-based consortia have led to some of the most impactful proposals being funded over the analysed time period. New pharmaceuticals, small molecules and monoclonal antibodies alike, along with screening and prevention, have been the most prominent sources of innovation in BC and PC, extending patients' survival and enhancing their quality of life. Unlike oncology, dementia drug development has been way less successful, with only minor improvements related to the quality of supportive medical care for symptoms and more sensitive diagnostics, without any ground-breaking disease-modifying treatment(s). Significant progresses in imaging diagnostics and nanotechnology have been largely driven by the participation of medical device industry multinational companies. Clinical trials funded by the EC were conducted, leading to the development of brand-new drug molecules featuring novel mechanisms of action. Some prominent cases of breakthrough discoveries serve as evidence for the European capability to generate cutting-edge technological innovation in biomedicine. Less productive areas of research may be reconsidered as priorities when shaping the new agenda for forthcoming science funding programmes. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most frequent localization of malignant process in American women and women of European countries. To date it is not possible to control the morbidity growth due to lack of effective ways of primary prevention. Comparing the incidence of breast cancer in developed countries with the countries of Asia and Africa, there is the fact of population predominance lesion in more urbanized countries. This suggests that the environment along with other factors, occupies a significant place in the initiation and progression of breast neoplasia. The impressive rates of industrial development led to the pollution of soil, surface water and, as a consequence, food by heavy metal salts. The purposes of this paper are as follows: the chemical composition determination of neoplastic breast tissue, evaluation of the DNA methylation level, study of prognostic-important receptors expression in the breast cancer cells, establishing linkages between all the derived indicators. Methods: In our study we used the following methods: studying of the chemical composition of breast cancer tissue by atomic absorption spectrophotometry and energy-dispersion spectrometer; immunohistochemical study of ER, PR, HER2/neu, p53, Ki-67, E-cadherin and MGMT receptors; DNA extraction and investigation by oscillating infrared spectroscopy method. Results: The total amount of heavy metals in breast cancer tissue ranged from 51.21 x 10-3 to 84.86 x 10-3 µg/kg. We have got the following results: the growth of heavy metals in neoplastic tissue is accompanied with the increase of HER2/neu, p53, Ki-67, MGMT expression and decrease of ER and PR expression. The increment of pathological DNA methylation is accompanied with the increasing amount of heavy metals in tumor tissue. Conclusions: Heavy metals through different pathogenetic links stimulate the progression of breast cancer and reduce its sensitivity to treatment. DNA of tumor tissue has a different level of methylation which changes with the amount of heavy metals in cancer cells. This is displayed on the synthesis of prognostically important receptors in neoplastic tissue. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a significant health concern among European women, with the highest prevalence rates among all cancers. Existing BC prediction models account for major risks such as hereditary, hormonal and reproductive factors, but research suggests that adherence to a healthy lifestyle can reduce the risk of developing BC to some extent. Understanding the influence and predictive role of lifestyle variables in current risk prediction models could help identify actionable, modifiable, targets among high-risk population groups. Purpose: To systematically review population-based BC risk prediction models applicable to European populations and identify lifestyle predictors and their corresponding parameter values for a better understanding of their relative contribution to the prediction of incident BC. Methods: A systematic review was conducted in PubMed, Embase and Web of Science from January 2000 to August 2021. Risk prediction models were included if (i) developed and/or validated in adult cancer-free women in Europe, (ii) based on easily ascertained information, and (iii) reported models' final predictors. To investigate further the comparability of lifestyle predictors across models, estimates were standardised into risk ratios and visualised using forest plots. Results: From a total of 49 studies, 33 models were developed and 22 different existing models, mostly from Gail (22 studies) and Tyrer-Cuzick and co-workers (12 studies) were validated or modified for European populations. Family history of BC was the most frequently included predictor (31 models), while body mass index (BMI) and alcohol consumption (26 and 21 models, respectively) were the lifestyle predictors most often included, followed by smoking and physical activity (7 and 6 models respectively). Overall, for lifestyle predictors, their modest predictive contribution was greater for riskier lifestyle levels, though highly variable model estimates across different models. Conclusions: Given the increasing BC incidence rates in Europe, risk models utilising readily available risk factors could greatly aid in widening the population coverage of screening efforts, while the addition of lifestyle factors could help improving model performance and serve as intervention targets of prevention programmes. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common cancer globally among women, with 2,261,419 new cases in 2020; systemic treatment may be neo-adjuvant, adjuvant, or both. BC subtype guides the standard systemic therapy administered, which consists of endocrine therapy for all HR + tumors, trastuzumab-based HER2-directed antibody therapy plus chemotherapy for all HER2 + tumors (with endocrine therapy given in addition, if concurrent HR positivity), and chemotherapy alone for the triple-negative subtype. This study aimed to identify, evaluate, and systematically review all budget impact analyses (BIAs) of BC medications worldwide. Methods: PubMed, Scopus, and Web of Science Core Collection databases were thoroughly searched up to 26th March 2022 to identify original published studies which evaluate BIA of BC medications. ISPOR Task Force guidelines were used to assess the quality of included studies. This study was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: In total, 17 BIAs were included in the study. About half of the studies were conducted in Europe. The results of the BIAs showed that most of the included BIAs are conducted from the payer's perspective; they have different methodological frameworks for recommended chemotherapy, targeted therapy, and immunotherapy agents to treat BC. For the same medications, the results of budgetary effects are not consistent in diverse countries. Nine out of the 17 studies were focused on trastuzumab, in which the biosimilar form reduced costs, but the brand form increased costs, especially in a 52-week treatment period. Conclusion: Researchers should conduct the budget impact analysis of high-value medications such as anti-tumor drugs more objectively, and the accuracy of parameters needs to be more strictly guaranteed. Furthermore, it is worthy of declaring that the budgetary impact of the same drug is not always consistent over time, so the researchers should measure access to medication in the long run. [ABSTRACT FROM AUTHOR]

Background: The correlation between benign thyroid disease (BTD) and breast cancer (BC) has long been discussed. However, the definite relationship and potential mechanism between them are still disputed. The current metaanalysis aimed at performing a comprehensive assessment of the relationship between different types of benign thyroid disease and the risk of breast cancer, furthermore, assessing whether benign thyroid disease exerts an influence on the aggressiveness of breast cancer. Method: A systematic literature search (PubMed, Web of Science, MEDLINE, and Embase databases) identified studies to evaluate the correlation between BTD and BC risk. Data were analyzed using version 16.0 STATA software, including the odds ratio (OR) and its corresponding 95% confidence intervals (CIs). Publication bias and quality assessment were conducted for the included studies. Result: Overall, 18 studies involving 422,384 patients with BTD were incorporated. The outcome showed that autoimmune thyroiditis (OR: 2.56, 95%CI: 1.95-3.37, I2 = 0.0%, p=0.460), goiter (OR: 2.13, 95%CI: 1.19-3.79, I2 = 80.6%, p=0.000), and Graves' disease (OR: 5.01, 95%CI: 1.49-16.82, I2 = 0.0%, p=0.358) was connected with a higher risk of BC. Both hypothyroidism (OR: 0.82, 95%CI: 0.64-1.04, I2 = 85.0%, p=0.000) and hyperthyroidism (OR: 1.07, 95%CI: 0.93-1.24, I2 = 24.9%, p=0.206) had no significant association with the risk of BC. Additionally, the pooled analysis showed no apparent correlation between BTD and aggressiveness of BC. However, subgroup analysis indicated a positive relationship between BTD and aggressiveness of BC in the Europe subgroup (HR: 2.05, 95%CI: 1.32-3.17, I2 = 86.4%, p=0.000). Conclusion: Autoimmune thyroiditis, goiter, and Graves' disease are connected with an increased risk of BC. Furthermore, subgroup analysis suggested that BTD increases the aggressiveness of BC in the European population geographically. Nevertheless, further research is needed to prove these discoveries. [ABSTRACT FROM AUTHOR]

Scorzonera hispanica is an herbaceous perennial cultivated in Central and Southern Europe. This study aimed to qualitatively and quantitatively evaluate the composition of oil, extracts, and fractions (SH1-SH12) obtained from S. hispanica seeds. Furthermore, an evaluation of biological activities in breast cancer cell lines was also performed. GC-MS analysis revealed that the primary components of the seed oil (SH12) were fatty acids and β-sitosterol. In the evaluation of extracts (SH1-SH3, SH8-SH10) and fractions (SH4-SH7, SH11) composition, the presence of apigenin, derivatives of p-coumaric and caffeic acids, was reported. In the biological assays, methanolic extract (SH1), diethyl ether (SH4), and chloroform (SH11) fractions exhibited cytotoxicity toward cells. The highest activity was observed for fatty acids- and 3,4-dimethoxycinnamate-rich SH11 (IC50: 399.18 μg/mL for MCF-7, 781.26 μg/mL for MDA-MB-231). SH11 was also observed to induce apoptosis in MCF-7 cells (52.4%). SH1, SH4, and SH11 attenuate signaling pathways and affect the expression of apoptosis-, autophagy-, and inflammation-related proteins. SH12 was non-toxic toward either cancer or normal cell lines in concentrations up to 1 mg/mL. The results suggest that S. hispanica seeds exhibit a wide range of potential uses as a source of oil and bioactive compounds for complementary therapy of breast cancer. [ABSTRACT FROM AUTHOR]

Hadron therapy with protons and carbon ions is widely attracting interest as a potential competitor of conventional photon radiotherapy. Exquisite dose distribution of charged particles allows for a higher local control of the tumor and lower probability of damage to nearby healthy tissues. Heavy ions have presumed biological advantages rising from their high-linear energy transfer (LET) characteristics, including greater cell-killing effectiveness and reduced heterogeneity dependence of radiation response. Although these advantages are clear and supported by data, only 18.0% of proton and carbon ion radiotherapy (CIRT) facilities in Europe are treating breast cancers. This review summarizes the physical and radiobiological properties of charged particles, clinical use of particle beam for breast cancer, and suggested approaches to overcome technical and financial challenges. [ABSTRACT FROM AUTHOR]

Background: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort.Methods: Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI).Results: After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93-1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73-0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94-1.05).Conclusions: While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies. [ABSTRACT FROM AUTHOR]

Background: Comparisons of outcomes of health care in different systems can be used to inform health policy. The EuroHOPE (European Healthcare Outcomes, Performance and Efficiency) project investigated the feasibility of comparing routine data on selected conditions including breast cancer across participating European countries. Methods: Routine data on incidence, treatment and mortality by age and clinical characteristics for breast cancer in women over 24years of age were obtained (for a calendar year) from linked hospital discharge records, cancer and death registers from Finland, the Turin metropolitan area, Scotland and Sweden (all 2005), Hungary (2006) and Norway (2009). Age-adjusted breast cancer incidence and 1-year survival were estimated for each country/region. Results: In total, 24576 invasive breast cancer cases were identified from cancer registries from over 13 million women. Age-adjusted incidence ranged from 151.1 (95%CI 147.2-155.0) in Hungary to 234.7 (95%CI 227.4-242.0)/100 000 in Scotland. One-year survival ranged from 94.1% (95%CI 93.5-94.7%) in Scotland to 97.1% (95%CI 96.298.1%) in Italy. Scotland had the highest proportions of poor prognostic factors in terms of tumour size, nodal status and metastases. Significant variations in data completeness for prognostic factors prevented adjustment for case mix. Conclusion: Incidence of and survival from breast cancer showed large differences between countries. Substantial improvements in the use of internationally recognised common terminology, standardised data coding and data completeness for prognostic indicators are required before international comparisons of routine data can be used to inform health policy. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to identify European radiographers' challenges in clinical performance in mammography and the main areas of mammography that require more and better training. Methods: An extensive search was performed to identify relevant studies focused on clinical practice, education and training in mammography published between January 2010 and December 2015 in the English language. The data were analysed by using deductive thematic analysis. Results: A total of 27 full text articles were read, evaluating their quality. Sixteen articles out of 27 were finally selected for this integrative review. The main challenges of radiographers' mammography education/training can be divided into three groups: training needs, challenges related to radiographers, and challenges related to the organization of education. The most common challenges of clinical performance in mammography among European radiographers involved technical performance, the quality of practices, and patient-centeredness. Conclusions: The introduction of harmonized mammography guidelines across Europe may serve as an evidence-based tool to be implemented in practice and education. However, the variability in human and material resources as well as the different cultural contexts should be considered during this process. Teaching Points : • Radiographers' awareness of their professional identity and enhancing multiprofessional cooperation in mammography. • Radiographers' responsibilities regarding image quality (IQ) and optimal breast imaging performance. • Patient-centred mammography services focusing on the psychosocial needs of the patient. • Challenges: positioning, QC-testing, IQ-assessment, optimization of breast compression, communication, teamwork, and patient-centred care. • Introduction of evidence-based guidelines in Europe to harmonize mammography practice and education. [ABSTRACT FROM AUTHOR]

Objective: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology.Design: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison.Setting: The European Prospective Investigation into Cancer and Nutrition (EPIC).Subjects: Women (n 334 850) from the EPIC study.Results: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01).Conclusions: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC. [ABSTRACT FROM AUTHOR]