Mastectomy or breast conserving surgery? Factors affecting type of surgical treatment for breast cancer – a classification tree approach

BACKGROUND: A critical choice facing breast cancer patients is which surgical treatment – mastectomy or breast conserving surgery (BCS) – is most appropriate. Several studies have investigated factors that impact the type of surgery chosen, identifying features such as place of residence, age at diagnosis, tumor size, socio-economic and racial/ethnic elements as relevant. Such assessment of "propensity" is important in understanding issues such as a reported under-utilisation of BCS among women for whom such treatment was not contraindicated. Using Western Australian (WA) data, we further examine the factors associated with the type of surgical treatment for breast cancer using a classification tree approach. This approach deals naturally with complicated interactions between factors, and so allows flexible and interpretable models for treatment choice to be built that add to the current understanding of this complex decision process. METHODS: Data was extracted from the WA Cancer Registry on women diagnosed with breast cancer in WA from 1990 to 2000. Subjects' treatment preferences were predicted from covariates using both classification trees and logistic regression. RESULTS: Tumor size was the primary determinant of patient choice, subjects with tumors smaller than 20 mm in diameter preferring BCS. For subjects with tumors greater than 20 mm in diameter factors such as patient age, nodal status, and tumor histology become relevant as predictors of patient choice. CONCLUSION: Classification trees perform as well as logistic regression for predicting patient choice, but are much easier to interpret for clinical use. The selected tree can inform clinicians' advice to patients

Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer

The generation of antitumour immunity depends on the nature of dendritic cell (DC)–tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n=137) and advanced (stage IV, n=36) disease compared to healthy controls (n=66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy

Human skin penetration of a copper tripeptide in vitro as a function of skin layer

We study a set of 28 GRB light-curves detected between 15 December 2002 and 9 June 2003 by the anti-coincidence shield of the spectrometer (SPI) of INTEGRAL. During this period it has detected 50 bursts, that have been confirmed by other instruments, with a time resolution of 50 ms. First, we derive the basic characteristics of the bursts: various duration measures, the count peak flux and the count fluence. Second, a sub-sample of 11 bursts with 12 individual, well-separated pulses is studied. We fit the pulse shape with a model by Kocevski et al. (2003) and find that the pulses are quite self-similar in shape. There is also a weak tendency for the pulses with steep power-law decays to be more asymmetric. Third, the variability of the complex light-curves is studied by analyzing their power-density-spectra (PDS) and their RMS variability.
The averaged PDS, of the whole sample, is a power-law with index of $1.60\pm0.05$ and a break between 1–2 Hz. Fourth, we also discuss the background and noise levels. We found that the background noise has a Gaussian distribution and its power is independent of frequency, i.e., it is white noise. However, it does not follow a Poisson statistic since on average the variance is ~1.6 larger than the mean. We discuss our results in context of the current theoretical picture in which GRBs are created in an anisotropic, highly relativistic outflow from collapsing massive stars. Finally, we note that the exact behaviour of the instrument is not yet known and therefore the above results should be treated as preliminary.

Human skin penetration of a copper tripeptide in vitro as a function of skin layer

Objective and designSkin retention and penetration by copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent.Materials and methodsFlow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. copper tripeptide as permeant was applied on isolated stratum corneum, heat-separated epidermis and dermatomed skin and receptor fluid collected over 48 h in 4 h intervals using inductively coupled plasma mass spectrometry to analyze for copper in tissues and receptor fluid.ResultsThe permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 97 ± 6.6 μg/cm(2) were retained as depot.ConclusionsCopper as tripeptide was delivered in potentially therapeutically effective amounts for inflammatory disease

Prognostic significance of tumor-infiltrating lymphocytes in ductal carcinoma in situ of the breast

Tumor-infiltrating lymphocytes (TILs) provide prognostic value in invasive breast cancer and guidelines for their assessment have been published. This study aims to evaluate: (a) methods of TILs assessment, and (b) their prognostic significance in breast ductal carcinoma in situ (DCIS). Hematoxylin and eosin sections from two clinically annotated DCIS cohorts; a training set (n = 150 pure DCIS) and a validation set (n = 666 comprising 534 pure DCIS and 132 cases wherein DCIS and invasive breast carcinoma were co-existent) were assessed. Seven different scoring methods were applied to the training set to identify the most optimal reproducible method associated with strongest prognostic value. Among different methods, TILs touching ducts' basement membrane or away from it by one lymphocyte cell thickness provided the strongest significant association with outcome and highest concordance rate [inter-cluster correlation coefficient = 0.95]. Assessment of periductal TILs at increasing distances from DCIS (0.2 , 0.5 , and 1 mm) as well as percent of stromal TILs were practically challenging and showed lower concordance rates than touching TILs. TILs hotspots and lymphoid follicles did not show prognostic significance. Within the pure DCIS validation set, dense TILs were associated with younger age, symptomatic presentation, larger size, higher nuclear grade, comedo necrosis and estrogen receptor negativity as well as shorter recurrence-free interval (p = 0.002). In multivariate survival analysis, dense TILs were independent predictor of shorter recurrence-free interval (p = 0.002) in patients treated with breast conservation. DCIS associated with invasive carcinoma showed denser TILs than pure DCIS (p = 9.0 × 10-13). Dense TILs is an independent prognostic variable in DCIS. Touching TILs provides a reproducible method for their assessment that can potentially be used to guide management

How are compassion fatigue, burnout, and compassion satisfaction affected by quality of working life? Findings from a survey of mental health staff in Italy

BACKGROUND: Quality of working life includes elements such as autonomy, trust, ergonomics, participation, job complexity, and work-life balance. The overarching aim of this study was to investigate if and how quality of working life affects Compassion Fatigue, Burnout, and Compassion Satisfaction among mental health practitioners. METHODS: Staff working in three Italian Mental Health Departments completed the Professional Quality of Life Scale, measuring Compassion Fatigue, Burnout, and Compassion Satisfaction, and the Quality of Working Life Questionnaire. The latter was used to collect socio-demographics, occupational characteristics and 13 indicators of quality of working life. Multiple regressions controlling for other variables were undertaken to predict Compassion Fatigue, Burnout, and Compassion Satisfaction. RESULTS: Four hundred questionnaires were completed. In bivariate analyses, experiencing more ergonomic problems, perceiving risks for the future, a higher impact of work on life, and lower levels of trust and of perceived quality of meetings were associated with poorer outcomes. Multivariate analysis showed that (a) ergonomic problems and impact of work on life predicted higher levels of both Compassion Fatigue and Burnout; (b) impact of life on work was associated with Compassion Fatigue and lower levels of trust and perceiving more risks for the future with Burnout only; (c) perceived quality of meetings, need of training, and perceiving no risks for the future predicted higher levels of Compassion Satisfaction. CONCLUSIONS: In order to provide adequate mental health services, service providers need to give their employees adequate ergonomic conditions, giving special attention to time pressures. Building trustful relationships with management and within the teams is also crucial. Training and meetings are other important targets for potential improvement. Additionally, insecurity about the future should be addressed as it can affect both Burnout and Compassion Satisfaction. Finally, strategies to reduce possible work-life conflicts need to be considered

Do serum biomarkers really measure breast cancer?

Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.United States. Dept. of Defense. Breast Cancer Research Program (Grant No. W81XWH-05-1-0292)National Institutes of Health (U.S.) (R01 CA-112437-01)National Institutes of Health (U.S.) (NIH CA 84955