Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study.

PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

CXCL8 secretion by dendritic cells predicts contact allergens from irritants.

Monocyte-derived dendritic cell functions have been explored for identification of contact allergens in vitro. Current methods, including measurement of changes in cell surface marker expression (e.g. CD83, CD86) do not provide a sensitive method for detecting the sensitising potential of a chemical. In this study, we investigated whether chemokine production by monocyte-derived dendritic cells is increased upon maturation and whether chemokine production can provide methodology for the detection of allergens. Monocyte-derived dendritic cells were exposed to allergens (nickel sulphate, cobalt chloride, palladium chloride, copper sulphate, chrome-(III)-chloride, potassium dichromate, p-phenylenediamine and dinitrochlorobenzene) and irritants (sodium dodecyl sulphate, dimethylsulphoxide, benzalkoniumchloride and propane-1-ol). CD83 and CD86 expression was analysed by flow cytometry and chemokine production (CXCL8, CCL5, CCL17, CCL18, CCL19, CCL20, CCL22) was determined by ELISA. Significant up regulation of CD83 and CD86 expression could only be induced by three out of seven and five out of seven allergens, respectively. In contrast, CXCL8 production was significantly increased after stimulation with all allergens tested, whereas irritant exposure led to decreased CXCL8 production. All other chemokines tested, failed in identifying contact allergens. In conclusion, CXCL8 production, next to CD83 and CD86 up regulation, by monocyte-derived dendritic cells provides a promising in vitro tool for discrimination between allergens and irritants.

Accuracy of frozen-section analysis in the diagnosis of ovarian tumors: a systematic quantitative review.

A quantitative systematic review was performed to estimate the diagnostic accuracy of frozen sections in ovarian tumors. Studies that compared frozen sections and paraffin sections within subjects for diagnosis of ovarian tumors were included. Fourteen primary studies were analyzed, which included 3 659 women. For benign ovarian vs borderline/malignant tumor cases, the occurrence of a positive frozen-section result for benignity (pooled likelihood ratio [LR], 8.7; 95% confidence interval [CI], 7.3-10.4) and posttest probability for benign diagnosis was 95% (95% CI, 94-96%). A positive frozen-section result for malignant vs benign diagnosis (pooled LR, 303; 95% CI, 101-605) increased the probability of ovarian cancer to 98% (95% CI, 97-99%). In borderline vs benign ovarian tumor cases, a positive frozen-section result (pooled LR, 69; 95% CI, 45-106) increased the probability of borderline tumors to 79% (95% CI, 71-85%). In borderline vs malignant ovarian tumor cases, a positive frozen-section result (pooled LR, 18; 95% CI, 13-26) increased the probability of borderline tumors to 51% (95% CI, 42-60%). We conclude that diagnostic accuracy rates for frozen-section analysis is high for malignant and benign ovarian tumors, but the accuracy rates in borderline tumors remain relatively low.

Extended neoadjuvant chemotherapy in locally advanced breast cancer combined with GM-CSF: effect on tumour-draining lymph node dendritic cells.

The effect of long-term administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) on dendritic cell (DC) activation and survival in patients with locally advanced breast cancer (LABC) was studied. To this end, the number of activated DC (i.e. positive for the marker S100) in tumour-draining lymph nodes (TDLN) was determined and compared between LABC patients receiving neoadjuvant chemotherapy with GM-CSF (n=52) or without GM-CSF (n=11), and a control group of chemonaïve breast cancer patients (n=10). A significantly higher mean percentage of S100+ DC in the TDLN of the GM-CSF-treated patients (9.9%) was found compared with each of the respective control groups (5.3 and 5.1%, P=0.002). Moreover, intrapatient comparison before and after treatment showed that the percentage of S100+ DC significantly increased over the course of the GM-CSF treatment (P=0.018). In a univariate survival analysis with a median follow-up of 64 months, relatively high percentages of S100+ DC (> or =8%) were associated with a longer disease-free survival (DFS) (P=0.078). In patients with a high tumour load, where immunosuppressed conditions generally prevail, long-term administration of GM-CSF may thus contribute to survival through enhanced DC activation and consequently improved chances of effective antitumour immunity.

Mortalidade por câncer de colo uterino no Rio Grande do Sul / Mortality from uterine cervix neoplasm in Rio Grande do Sul

O objetivo deste estudo refere-se a mortalidade por câncer do colo uterino (Cid 180), através da verificaçäo dos coeficientes de mortalidade no Rio Grande os Sul e nas 24 microrregiöes que compöem o referido Estado, com estudo das tendências (regressäo linear simples), período de 1970 a 1989. Como objetivos secundários foram abordados a feqüência relativa desta neoplasia em relaçäo ao total de óbitos por neoplasias malignas, estudo comparativo com outras localidades e correlaçäo com fatores de risco. Os dados que permitiram este estudo foram obtidos na Secretaria de Saúde e Meio Ambiente do Rio Grande do Sul, Instituto Brasileiro de Geografia e Estatística IBGE), Ministério de Saúde e Organizaçäo Mundial de Saúde. A média dos coeficientes de mortalidade/100.000 mulheres no Rio Grande do Sul (1970-1989) foi de 3,8, com tendência ascendente. Observaram-se diferenças importantes na distribuiçäo dos coeficientes de mortalidade nas 24 microrregiöes do Estado, com médias oscilando entre 2,5 e 6,7. O câncer de colo uterino ocupou o 4§ lugar na mortalidade por neoplasias entre as mulheres do Rio Grande do Sul, em 1989. Vírus de papiloma humano e tabagismo säo importantes fatores de risco nesta neoplasia

[Mortality from uterine cervix cancer in Rio Grande do Sul]. / Mortalidade por câncer de colo uterino no Rio Grande do Sul.

The mortality from cervical cancer was studied by checking the death rates in Rio Grande do Sul (RS) and in its 24 microregions. Each tendency (linear regression), in the period from 1970 to 1989, was also investigated. We have also studied the relative rates of this kind of cancer, the comparison with the rate in other places and the risk factors. The data were obtained at the Office of Health in Rio Grande do Sul as well as in the Statistics and Geography Brazilian Institute and World Health Organization. The average mortality rates/100,000 women in RS (1970-1989) was 3.8, with ascending tendency. Important differences in the death rates in the 24 microregions in RS were observed and they ranged from 2.5 to 6.7. The cervical cancer was the fourth cause of death in women from RS (mortality by cancer), in 1989. Papillomaviruses and smoking were important factors in the development of cervical cancer.

[Smoking in Porto Alegre: prevalence and the role of health professionals in its prevention]. / Tabagismo em Porto Alegre: prevalência e o papel dos profissionais da saúde na prevenção.

This study was undertaken in 1988 in order to evaluate the prevalence of smoking, the degree of awareness of smokers and ex-smokers to risks of smoking, and the role of health professionals in the control of smoking in Porto Alegre. A total of 407 persons between 15 and 64 years were interviewed in a population-based survey. Of these, 170 (41.8%) smoked. Among ex-smokers, 85.7% stopped due to awareness of the harm that cigarettes can cause. Only 16.5% of smokers and ex-smokers were warned to the risks of smoking by health professionals before acquiring the habit. After becoming smokers, only 51.4% were warned. These indices are a cause for concern as we believe that prevention is the best approach to control of the smoking epidemic.