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Background: The benefit of pathologic complete response (pCR) in early breast cancer (eBC) is not well described in the real-world setting. This study used the nationwide Flatiron Health electronic health record-derived deidentified database to describe treatment patterns and survival outcomes by pCR status after neoadjuvant therapy (NAT) in women with triple-negative or HR+/HER2- eBC. Materials & methods: Observational cohort study analyzing women with eBC who started NAT between 2011 and 2018. Results: 496 women were included in the study; of those, 16.1% achieved pCR, of which 35.7% were triple-negative and 6.1% were HR+/HER2- eBC. More women with triple-negative eBC (95.2%) were exclusively treated with chemotherapy-based NAT versus HR+/HER2- eBC (56.1%). In multivariate analyses from NAT start, not achieving pCR was associated with increased risk of death and progression. Conclusion: pCR status may be a reliable prognostic indicator for survival in these eBC subtypes in the real-world setting.

Disease free survival (DFS) and overall survival (OS) analysis according to AR mRNA expression levels in BC subtypes

Data sets for gene-expression analysis with patients' and tumours' characteristics from the neoadjuvant studies

Supplementary Tables and Figures legend

PRISMA flow chart for studies involved in clinical meta-analysis Study flow chart for gene expression pooled analysis

Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain.Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a meta-analysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms “breast neoplasm” and “androgen receptor” and were selected after a qualitative assessment based on the REMARK criteria. A pooled gene expression analysis of 35 publicly available microarray data sets was also performed from patients with early-stage breast cancer with available gene expression and clinical outcome data.Results: Twenty-two of 33 eligible studies for the clinical meta-analysis, including 10,004 patients, were considered as evaluable for the current study after the qualitative assessment. AR positivity defined by IHC was associated with improved DFS in all patients with breast cancer [multivariate (M) analysis, HR 0.46; 95% confidence interval (CI) 0.37–0.58, P < 0.001] and better OS [M-HR 0.53; 95% CI, 0.38–0.73, P < 0.001]. Thirty-five datasets including 7,220 patients were eligible for the pooled gene expression analysis. High AR mRNA levels were found to confer positive prognosis overall in terms of DFS (HR 0.82; 95% CI 0.72–0.92;P = 0.0007) and OS (HR 0.84; 95% CI, 0.75–0.94; P = 0.02) only in univariate analysis.Conclusions: Our analysis, conducted among more than 17,000 women with early-stage breast cancer included in clinical and gene expression analysis, demonstrates that AR positivity is associated with favorable clinical outcome. Clin Cancer Res; 23(11); 2702–12. ©2016 AACR.

Association of AR mRNA levels and individual genes and gene signatures (GS) in all BC patients

Correlation of clinical variables and AR expression in different BC subtypes: A-in Luminal A; B-in Luminal B; C-in HER2 enriched; D-in Basal like.

Data sets for gene-expression analysis with patients' and tumours' characteristics

Main characteristics of evaluable clinical studies included in meta-analysis for disease free survival (DFS) and overall survival (OS)

REMARK scores of eligible studies for clinical meta-analysis

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer; Immuno-oncologia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer; Inmuno-oncología Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; Immuno-oncology The coronavirus disease-2019 (COVID-19) pandemic has had a significant impact on patients with underlying malignancy. In this article, we summarize emerging data related to patients with cancer and COVID-19. Among patients with COVID-19, a higher proportion have an underlying diagnosis of cancer than seen in the general population. Also, patients with malignancy are likely to be more vulnerable than the general population to contracting COVID-19. Mortality is significantly higher in patients with both cancer and COVID-19 compared with the overall COVID-19-positive population. The early months of the pandemic saw a decrease in cancer screening and diagnosis, as well as postponement of standard treatments, which could lead to excess deaths from cancer in the future. No funding was received from any source. No Rapid Service Fee was received by the journal for the publication of this article.

The speed and spread of the COVID-19 pandemic has been affecting the entire world for the past several months. OncoAlert is a social media network made up of more than 140 oncology stakeholders: oncologists (medical, radiation, and surgical), oncology nurses, and patient advocates who share the mission of fighting cancer by means of education and dissemination of information. As a response to the COVID-19 pandemic, OncoAlert hosted The Round Table Discussions. We have documented this effort along with further discussion about the COVID-19 pandemic and the consequences on patients living with cancer to disseminate this information to our colleagues worldwide. ispartof: JCO GLOBAL ONCOLOGY vol:7 pages:455-463 ispartof: location:United States status: published

Microsatellite instability (MSI) and POLD1 mutations are usually described in colorectal tumours in patients with polyposis syndrome but rarely found in breast tumours. This case describes a metastatic luminal B breast tumour in a young patient with an important family history of cancer. Mutational studies found a Variant of Uncertain Significance (VUS)-type alteration in POLD1 that motivated the study for MSI, which was found positive. Recent data point towards the use of pembrolizumab as a treatment option for tumour presenting with MSI instead of chemotherapy.

e19261 Background: MDTB have emerged as a valuable forum to address questions related to patient management. There is a general data lack of its overall benefit by attending physicians. However, few reports describe numerical impact on patient care of this tailor-made and shared model of medical decision. Methods: We describe, in this prospectively-collected study, data from a Cancer Center (HAOC) regarding multiple weekly, 1h-long discussions, as part of MDTB (GU, neuro-oncology GI, thorax, HN, breast, gyneco, melanoma/sarcoma and palliative care). Only newly-diagnosed or on-treatment challenging cancer cases were included. Attendees (onco, surgeons, RT, paths and radiologists) pooled their expertise to warrant quality and maximize resources. The primary endpoint was change in the medical planning. In our institution, further adherence to MDTB recommendations are left totally at physician discretion. Results: From Oct/17 to Feb/19, 413 cases were discussed (60% female), mean of 2.9 cases/MDTB, but GI (3.8), thorax (3.7) and breast (2.94) were above the median. Mean was 13.4 doctors/MDTB - more in breast (16.5), GI (15.8) and uro (15.1). Mean of oncologist/MDTB in general was 6.1, but 8.1 in GI, 7.8 thorax, breast 6.8 and 6.7 uro. Mean of surgeons/MDTB in general was 3.5, but 6.2 in breast, 5.8 uro and 5.5 GI. 100% of all had at least 1 oncologist and uro/GI/breast had at least 1 surgeon in 100% of them. In 50% (uro), 44% (neuro), 23.5% (breast), 6.4% (thorax) and 3.7% (GI) had at least 1 physician of 5 major areas. Oncologists engaged with more cases: 80.4% (thorax), 70.6% (uro), 59.6% (GI), 56.5% (HN). Prostate (38.2%), metastasis (neuro, 28.9%), colorectal (18.2%), lung adenoCA (43.5%), mouth (30.4%), ductal carcinoma (35.8%) were the more frequently discussed per system. In 25.7%, MDTB changed original medical planning. By site: GI (35,6%), thorax (24,7%), breast (22,6%), neuro (21,7%), uro (17,7%) and HN (17,4%). Oncologists were responsible more in thorax (73,9%) and less in breast (33%) and surgeons more in breast (50%) and less in GI (33%). Adherence to NCCN guidelines was total. Finally, but not measurable, a sizeable number of cases requires significant weekly time-effort. Conclusions: This study confirms MDTB leading role in cancer care, highlighting the importance of teamwork for more precise patient care. We point out that it led to substantial practice-changing in our institution, reinforcing its importance in a scenario which doctors are confronted with increasing complexities in patient management.

Background: Neoadjuvant chemotherapy delivered with trastuzumab (NCT) has been shown to increase the rates of pathological complete response (pCR) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting has been associated with improved event free survival (EFS). However, no study has yet investigated the effect on outcomes of NCT compared to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT). This study sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early breast cancer. Methods: Women with HER2 positive invasive breast cancers treated with neoadjuvant chemotherapy between 2006-2010 were identified at each of 7 European institutions and the case notes reviewed. Preoperative clinical, radiological and pathological details, treatment details and pathology results following breast surgery were reviewed. To be defined as NCT at least one dose of trastuzumab needed to be given preoperatively. pCR was defined as absence of invasive disease in breast and lymph nodes. Multivariable Cox regression and logistic regression were used to Survival outcomes for event-free survival (EFS) were calculated by log rank analysis model the influence of a number of factors on event-free survival (EFS) and pCR respectively. Results: 236 patients were identified; 138 (58%) received NCAT & 98 (42%) received NCT. The median follow up for the whole group was 53.7 months (IQR 41.7-68.8), 61.5 months (IQR 50.3-78.5) for NCAT group and 44.8 months (range 37-53.9) for NCT group. The 5-year EFS for NCAT vs NCT was 59.3% (95% CI: 49.8-67.6) and 69.6% (95% CI: 51.5-82.0) respectively. The unadjusted hazard ratio (HR) for EFS with NCT compared with the NCAT was 0.63 (95% CI 0.37–1.08; p=0.091). NCT significantly increased the odds of having pCR relative to NC (OR: 4.39 (2.18-8.86); p Conclusion Concomitant as compared to sequential trastuzumab is associated with improved outcomes in the neoadjvuant setting for women with ER negative tumours. These data further support the need for the early introduction of targeted combination therapy in women with ER negative/HER2 positive BC. Citation Format: Carlo Palmieri, Iain RJ Macpherson, Kelvin Yan, Felipe Ades Moraes, Pippa Riddle, Riz Ahmed, Waheeda Owadally, Barabara Stanley, Deep Shah, Ondrej Gojis, Adam Januszewski, Conrad Lewanski, Rebecca Asher, Daniel Lythgoe, Evandro De Azambuja, Mark Beresford, Sacha J Howell. Effects on outcome of concomitant neoadjuvant chemotherapy-trastuzumab compared with sequential neoadjuvant chemotherapy followed by post-operative trastuzumab [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-05.

Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain. Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a meta-analysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms “breast neoplasm” and “androgen receptor” and were selected after a qualitative assessment based on the REMARK criteria. A pooled gene expression analysis of 35 publicly available microarray data sets was also performed from patients with early-stage breast cancer with available gene expression and clinical outcome data. Results: Twenty-two of 33 eligible studies for the clinical meta-analysis, including 10,004 patients, were considered as evaluable for the current study after the qualitative assessment. AR positivity defined by IHC was associated with improved DFS in all patients with breast cancer [multivariate (M) analysis, HR 0.46; 95% confidence interval (CI) 0.37–0.58, P < 0.001] and better OS [M-HR 0.53; 95% CI, 0.38–0.73, P < 0.001]. Thirty-five datasets including 7,220 patients were eligible for the pooled gene expression analysis. High AR mRNA levels were found to confer positive prognosis overall in terms of DFS (HR 0.82; 95% CI 0.72–0.92;P = 0.0007) and OS (HR 0.84; 95% CI, 0.75–0.94; P = 0.02) only in univariate analysis. Conclusions: Our analysis, conducted among more than 17,000 women with early-stage breast cancer included in clinical and gene expression analysis, demonstrates that AR positivity is associated with favorable clinical outcome. Clin Cancer Res; 23(11); 2702–12. ©2016 AACR.

Background The development of trastuzumab is considered to be one of the greatest improvements in breast cancer treatment in recent years. This study aims to evaluate changes in the uptake of trastuzumab over the last 12 years and to determine whether its use is proportional to patient needs in the European Union and the USA. Methods Using national registry data, the number of new cases of HER2-positive breast cancer patients per year was estimated. The number of likely trastuzumab treatments per year was estimated using trastuzumab procurement data for each country. Results Western Europe and the USA show increasing procurement level of trastuzumab over the years studied, reaching proportional of use of trastuzumab few years after its marketing authorization in the early 2000's. After the approval in the adjuvant setting, in the year 2006, it was observed underuse of trastuzumab given the increase of the number of patients in need of treatment. Proportional use was shortly met after a couple of years. Few countries in Eastern Europe acquired the needed quantity of trastuzumab, with procurement levels starting to increase only after approval in the adjuvant setting in 2006. Conclusion Significant differences in trastuzumab procurement are observed between Western Europe, the USA and Eastern Europe, with the latter geographic region acquiring insufficient amounts of the drug required to treat all patients in need., SCOPUS: ar.j, info:eu-repo/semantics/published

The European Union (EU) is a confederation of 27 member states, the institutions of which work according to negotiated decisions. The EU has implemented similar legislation and a common market, and has adopted the same currency in most of its member states. Although financing health systems is a responsibility of the national governments, the EU has enacted the Charter of Fundamental Rights to standardize public health policies. However, for historical reasons, health policy and health expenditure is not uniform across the 27 EU member states (EU-27)., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the extracellular domain of this oncoprotein, represents the archetype of HER2 blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast cancer (BC) led to its clinical development in the adjuvant setting. The HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which proved that this compound can change the natural course of early stage HER2-positive BC. The HERA study led to the registration of trastuzumab for the adjuvant treatment of early HER2-positive BC. This trial randomized more than 5000 patients between 1 and 2 years of trastuzumab and observation after the completion of locoregional therapy and (neo)-adjuvant chemotherapy. Additionally, an abundance of subsequent substudies were conducted, addressing important clinical issues for this patient population. The present review article presents a comprehensive overview of the HERA study and its major contributions to the adjuvant treatment of HER2-positive BC patients. Emphasis is given on the lessons learned from this international collaborative experience and how this can be used as a stepping stone for further improvements in the field.

With the exception of endocrine therapy, no other systemic treatment of patients with breast cancer has reached such a magnitude of beneficial effect as trastuzumab. This targeted agent (monoclonal antibody) is associated with a significant improvement in both disease-free (DFS) and overall survival (OS) in women with HER-2 positive breast cancer when given in combination with or in sequence to adjuvant chemotherapy. This has been confirmed in a recent Cochrane meta-analysis of randomized controlled trials (RCTs), including 6 adjuvant and 2 neoadjuvant studies (NSABP B-31, NCCTG N9831, BCIRG 006, HERA, FinHer, PACS-04, Buzdar and NOAH), with data collection until February 2010. Overall, mortality is reduced by one-third and the risk of relapse by 40%.Concerns regarding cardiac dysfunction are declining, with reports indicating its reversibility in most instances, however truly long term cardiac evaluation is still lacking.Hence, the benefit of trastuzumab could be challenged by cardiac toxicity, in lower-risk patients [T1a,b node-negative (N0) tumors] or those with increased cardiovascular risk (older women and patients with previous significant heart disease/suboptimal left ventricular ejection fraction [LVEF (, SCOPUS: ar.j, info:eu-repo/semantics/published

The use of unproven forms of therapy in cancer treatment is very common. In Brazil, the distribution by researchers to patients of an investigational agent called phophoethanolamine (PHOS) has led to a widely publicized scientific scandal. PHOS is a precursor to components of the cell membrane, with some published pre-clinical studies suggesting cytotoxic activity in cancer cells. The willingness of courts and of legislators to guarantee access to PHOS in spite of the lack of any clinical data and against the recommendations of scientific and medical organisations underscores the risks that unproven agents pose to regulatory authorities, health care systems and patients, and bears resemblance to other cases such as the controversy surrounding the approval of zidovudine for AIDS treatment by the FDA., SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ed.j, info:eu-repo/semantics/published

This chapter covers the epidemiology of breast cancer, reproductive and non-reproductive risk factors, as well as aspects of the molecular biology and classification of breast cancer. It presents an overview of the major oncogenic signaling pathways in breast cancer, along with the major findings from next generation sequencing studies in breast cancer, and the role of gene expression signatures in predicting response to primary systemic therapy. The chapter also covers the pathology of breast cancer, and discusses the surgical management of breast cancer in detail. Furthermore, there is an overview of radiotherapy treatment strategies for breast cancer, which is followed by a detailed overview of the medical management of breast cancer with chemotherapy, endocrine therapy, targeted therapy, and bone-modifying agents. Finally, the multidisciplinary management of breast cancer is discussed using case studies.

SUMMARY HER2 positivity defines a molecular subtype of breast cancer with aggressive biological behavior. HER2 has been clinically validated as a prominent therapeutic target in breast cancer, and an abundance of data from clinical trials proving the efficacy of trastuzumab, a humanized anti-HER2 monoclonal antibody, has changed the natural history of this disease. Despite positive results from many trials, resistance to anti-HER2 agents inevitably occurs in both the metastatic and adjuvant settings. This clinical reality has led to the development of various other targeted agents designed to block the HER2 receptor. Similarly, attempts to elucidate the molecular mechanisms of resistance to the already established anti-HER2 agents have opened new therapeutic avenues with numerous promising agents. This review presents a comprehensive overview of the data available on anti-HER2-targeted agents other than trastuzumab, and describes both challenges and directions for the future.

An evaluation of the benefit-versus-risk of bevacizumab in the treatment of advanced breast cancer is timely and relevant. Recently, the US FDA has withdrawn the approval of bevacizumab as a therapeutic option for the treatment of advanced breast cancer, generating controversy in the scientific community. Although the pivotal study (Eastern Cooperative Oncology Group 2100 trial [E2100]) had shown doubling of the progression-free survival when bevacizumab was added to chemotherapy, this magnitude of benefit could not be replicated in subsequent studies. Furthermore, individual studies and meta-analyses failed to demonstrate an overall survival benefit with the addition of bevacizumab to different chemotherapy regimens. In addition, this agent is associated with an increased incidence of serious adverse events such as hypertension, congestive heart failure and thromboembolism, and its cost is likely to be a consideration in its use for many patients worldwide. Retrospective biomarker-based studies aiming to identify the subpopulation of patients most likely to benefit from the addition of bevacizumab to standard chemotherapy in breast cancer should be a research priority.

In recent years, with the rise of immunotherapeutic agents for cancer treatment, we have observed a paradigm shift in oncology drug development. One common problem accompanying such paradigm shifts is how to build research strategies to fit the mechanism of action of the newer compounds. Developing immunotherapy in oncology requires us to address the unique characteristics of immunotherapeutic agents and to provide adequate tools for their evaluation, including the adjustment of clinical trial endpoints. Immunotherapy creates patterns of response different from those of chemotherapy, and thus they are not captured by the traditional World Health Organisation (WHO) tumour response criteria or the RECIST. Revisiting the results of pembrolizumab in patients with melanoma can help to evaluate the efficacy of the immune-related response criteria (irRC) as the gold standard for evaluating the clinical response of immunologic agents in oncology.

Margaret Hutka1,*, Berta Sousa2, Felipe Ades3, Joost van de Vorst4, Pierluigi Bonomo5, Leticia De Mattos-Arruda6 1 Department of Medicine, The Royal Marsden NHS Foundation Trust, London, UK 2 Breast Unit, Champalimaud Cancer Center, Lisbon, Portugal 3 Breast Unit, Institut Jules Bordet, Universite Libre de Bruxelles, Belgium 4 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands 5 Radiation Oncology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy 6 Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona, Spain

BACKGROUND AND OBJECTIVES: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine involved in a broad-spectrum pathological events relevant to the immune system. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS). Crush syndrome has been described as the systemic manifestation of muscle cell damage resulting from pressing or crushing. There are few data about MIF and IL-6 in crush syndrome. The aim of this study was to report four cases of crush syndrome, measuring seric levels of MIF and IL-6 and its correlation with severity. CASES REPORTS: Four patients suffering from crush syndrome after an accident with an explosive artifact were enrolled in the study. APACHE II score was checked at admission. It was collected serum sample of these patients during six consecutive days. Serum MIF, IL-6 and creatine kinase (CK) were measured. Sepsis-related organ failure assessment (SOFA) score was evaluated concomitantly. Data were analyzed. CONCLUSIONS: The variations observed in the CK measures were followed by alterations in the cytokines' level and at the SOFA score, suggesting interdependence between those factors. Other articles have already demonstrated similar results. Although the use of cytokines as biomarkers of severity in trauma is matter of interest, we need large studies with a higher number of patients to validate this observation.

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC.

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step. Copyright, SCOPUS: ar.j, info:eu-repo/semantics/published

The European Union (EU) has adopted a common procedure for granting marketing authorisation for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their policies are diverse. We aimed to evaluate the time for trastuzumab reimbursement approval and its association to health expenditure, to health policy performance, to the availability of cost-effectiveness studies and to breast cancer outcome.Breast cancer outcome was estimated by the mortality/incidence (M/I) ratio. Trastuzumab reimbursement approval dates were provided by Roche. Spearman's rank correlation and Wilcoxon rank-sum test were used to evaluate associations and/or differences between the variables studied. Additional analyses were made by grouping countries according to compliance to the 180 day timeframe stipulated in the EU 89/105/EEC Directive for drug pricing and reimbursement.A statistically significant inverse and strong correlation between breast cancer M/I ratio and health expenditure (r(s)=-0.730, p0.001) and health policy performance (r(s)=-0.711, p0.001) was found, meaning the better the score and the higher the expenditure, the fewer patients died after a breast cancer diagnosis. Factors associated with trastuzumab faster reimbursement and compliance to the 89/105/EEC Directive were better health policy score, higher health expenditure and availability of cost-effectiveness studies.Higher health policy scores and health expenditure are associated with faster reimbursement of trastuzumab and better breast cancer outcome. Although the study design does not allow inference of causal associations, a marked difference is observed between Eastern and Western Europe, with long delays and increased breast cancer mortality identified in Eastern European countries.

Background: To explore the current clinical management of early-stage breast cancer (BC) patients, identify areas of controversy, and interrogate how treating physicians implement latest advances. Methods: We conducted a 27-item survey, disseminated in two stages: paper distribution at selected BC sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between the demographic characteristics of the participants and replies. Results: A total of 512 physicians from 79 countries participated in the study, accounting for 465 (91%) fully completed questionnaires. The majority of the participants were ESMO members (66%), medical oncologists (86.5%), and working in multidisciplinary teams (91.6%). Heterogeneous results were captured, such as the following: 40.9%of the participants consider no genetic test useful for making adjuvant treatment decisions; 15.3% consider PET-CT a useful imaging modality for staging; 68.8% consider that postmenopausal patients with hormone receptor positive disease should always be offered an aromatase inhibitor as part of their adjuvant therapy; 78.7% prefer to administer trastuzumab concurrently with the taxane component of chemotherapy; and 27% would consider bevacizumab in the neoadjuvant setting. The logistic regression analysis did not identify any strong predictor of the probability of giving a reply fully compatible with evidence in the literature. Conclusion: This survey captures clinical practice and whether the latest research advances are implemented in the treatment of early-stage BC by an extended number of physicians. Significant individual differences were found. Areas of controversy were detected, and they deserve further exploration in order to generate 'tailored' educational tools, with the final goal being the standardization of the treatment of early-stage BC patients. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Several breast cancer therapies can lead to cardiovascular toxicity: drugs such anthracyclines can cause permanent damage, anti-HER2 agents may cause transitory and reversible cardiac dysfunction and others, such as those used in endocrine therapy, primarily disturb lipid metabolism. Considering the seriousness of these complications, trials are now being conducted to address cardiotoxicity associated with new drugs; however, to fully understand their toxicity profiles, longer follow-up is needed. In this review, we compile the information available about cardiac toxicity related to well-established systemic breast cancer treatments, as well as newer drugs, including antiangiogenics, mTOR inhibitors and novel anti-HER2 agents. We also describe current and next generation cardiac biomarkers and functional tests that can optimize treatment and reduce and prevent the incidence of treatment-related cardiotoxicity. © 2014 Elsevier Ltd., SCOPUS: re.j, info:eu-repo/semantics/published

CupPrint® is a genomic signature able to identify 47 different cancer types. The aim of our study was to compare the accuracy of this genomic signature to that of a full clinical work-up in diagnosing the primary tumour site. Patients with newly diagnosed, untreated metastatic tumours were eligible for this trial. The clinical work-up and gene expression profiling on a biopsy from a metastatic site were started at the same time. The study was planned using a one-stage Fleming design. Patients in whom no primary site was diagnosed by the clinical work-up were excluded. Out of the 67 patients registered, the primary site was identified by clinical work-up in 36 patients, and diagnosis with CupPrint was obtained in 53. There were 31 evaluable patients with both clinical and CupPrint diagnoses, and out of these a similar diagnosis was obtained in 11 patients, i.e. the concordance rate was 35% (95% confidence interval: 19-55%). The median time to diagnosis through the clinical work-up was 48 days, and 10 days with CupPrint (P0·001). We concluded that in patients with newly diagnosed metastatic tumours, CupPrint has low accuracy in diagnosing the primary cancer site.

Although advances in cytotoxic treatments have been obtained in several neoplasias, in metastatic melanoma there was no drug able to significantly change the natural history of the disease in the last 30 years. In the last decade, translational research identified important mechanisms in malignant transformation, invasion, and progression. Signaling pathways can be abnormally activated by oncogenes. The identification of oncogenic mutated kinases implicated in this process provides an opportunity for new target therapies. The melanoma dependence on BRAF-mutated kinase allowed the development of inhibitors that produced major responses in clinical trials. This is the beginning of a novel class of drugs in metastatic melanoma; the identification of the transduction signaling networking and other "druggable" kinases is in active research. In this paper, we discuss the ongoing research on cellular signaling inhibition, resistance mechanisms, and strategies to overcome treatment failure. © 2012 Felipe Ades and Otto Metzger-Filho., SCOPUS: re.j, info:eu-repo/semantics/published

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine involved in a broad-spectrum pathological events relevant to the immune system. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS). Crush syndrome has been described as the systemic manifestation of muscle cell damage resulting from pressing or crushing. There are few data about MIF and IL-6 in crush syndrome. The aim of this study was to report four cases of crush syndrome, measuring seric levels of MIF and IL-6 and its correlation with severity.Four patients suffering from crush syndrome after an accident with an explosive artifact were enrolled in the study. APACHE II score was checked at admission. It was collected serum sample of these patients during six consecutive days. Serum MIF, IL-6 and creatine kinase (CK) were measured. Sepsis-related organ failure assessment (SOFA) score was evaluated concomitantly. Data were analyzed.The variations observed in the CK measures were followed by alterations in the cytokines' level and at the SOFA score, suggesting interdependence between those factors. Other articles have already demonstrated similar results. Although the use of cytokines as biomarkers of severity in trauma is matter of interest, we need large studies with a higher number of patients to validate this observation.

JUSTIFICATIVA E OBJETIVOS: As abelhas empregadas inicialmente na produção melífera eram de origem européia, sendo de baixa produtividade e mansas. Em 1956 foram trazidas espécies africanas com maior capacidade produtiva, porém extremamente agressivas. Houve soltura acidental destas abelhas na natureza e ocorreu cruzamento entre as espécies, gerando linhagem de abelhas africanizadas. O objetivo deste relato é sugerir uma padronização de atendimento a pacientes vítimas da síndrome de envenenamento dado o número crescente de casos de ataques maciços por estas abelhas e a literatura escassa sobre o assunto. RELATO DO CASO: Paciente do sexo masculino, 19 anos, que durante treinamento militar foi atacado por enxame de abelhas africanizadas. CONCLUSÕES: As abelhas africanizadas por serem muito agressivas, atacam suas vítimas com elevado numero de picadas inoculando grande quantidade de veneno. As reações às picadas podem variar desde reação inflamatória local em indivíduos não sensibilizados, reação de hipersensibilidade e choque anafilático em indivíduos sensibilizados ou síndrome de envenenamento, quando devido a grande quantidade de veneno inoculado, os efeitos tóxicos se sobrepõem à reação anafilática. O atendimento a este tipo de acidente deve ser o mais precoce possível, com a realização de suporte clínico adequado e remoção mecânica dos ferrões. A estabilização hemodinâmica é de suma importância. BACKGROUND AND OBJECTIVES: Honeybees first used in the honey production came from Europe. They were gentle but their productivity was very low. In 1956 it was brought from Africa some species of honeybees that were more productible but also extremely aggressive. There was an accidental release of those bees, that proliferated by hybridizing with the European honeybees generating a new specimen of bees: the Africanized honeybees. The objective of this article is to suggest a pattern of treatment for this poisoning syndrome, because of the crescent number of these attacks and a few data about it. CASE REPORT: Male, 19 years old, soldier that in the course of his military training was attacked by a swarm of Africanized honeybees. CONCLUSIONS: As the Africanized honeybees are very aggressive, they attack their victims with lots of stings releasing a large quantity of venom. The reactions to the stings can vary from a local inflammatory reaction in non sensibilized people, hipersensibility reaction and anaphylactic shock in sensibilized people and poisoning syndrome when there is a big amount of inoculated venom. The medical attendance to this kind of accident must be as fast as possible. It must be done an adequate clinical support and a quick mechanical remotion of the stingers. The hemodynamic stabilization is a very important point.