Immune responses in primary and metastatic breast cancer

Abstract Breast Cancer is a heterogeneous disease, which affects one in ten women in the UK today. Developments in recent years have led to earlier diagnosis and improved treatments and survival. However, mortality is still high and metastatic disease remains incurable. The role of the immune system in breast cancer has been questioned for over 100 years and more recently has led to major developments most notably in the form of Herceptin. Current evidence suggests that the immune system is stimulated by tumours to manifest a response. Many breast cancers show evidence of this immune response in the form of tumour infiltrating lymphocytes. However contradictory opinions exist as to whether this response is favourable for the host or not. The significance of the findings of many of these studies is limited by several factors, including small patient numbers and the fact that qualitative rather than quantitative assessments of tumour infiltrating lymphocytes have been used. The aims of this study were twofold: Firstly, we set out to develop a practical and efficient method for quantifying immune responses in tissue specimens and secondly, the main aim was to establish the significance of this response, by quantifying the tumour infiltrating lymphocytes in a group of patients with breast cancer, using a well designed study. Our patient group was derived from the Greater Glasgow Health Board database, which was established in 1995 to keep a record of all patients diagnosed with breast cancer in greater Glasgow area. We designed a case-control study to include patients, who were matched on the basis of several factors, recognised as having prognostic significance in breast cancer. The hypothesis to be tested was that metastatic relapse would be less likely in women with breast cancers in which a significant immune infiltrate was present, than in women with cancers in which there was no significant immune-cell infiltrate. We established a reliable and efficient method for immune cell quantification, which will be of value in future studies looking at the immuno-phenotype of the cells that comprise the inflammatory cell infiltrate. Additionally we found that most breast cancers show evidence of an immune cell infiltrate and that this response is likely to be protective

To thine own self be true : Championing liberal arts education in the 21st century

Edited volume celebrating of the legacy of former UMM Chancellor Sam Schuman

Quantifying tumour-infiltrating lymphocyte subsets : a practical immuno-histochemical method

Background: Efficient histological quantification of tumour-infiltrating T and B lymphocyte (TIL) subsets in archival tissues would greatly facilitate investigations of the role of TIL in human cancer biology. We sought to develop such a method. Methods: Ten ×40 digital images of 4 μ sections of 16 ductal invasive breast carcinomas immunostained for CD3, CD4, CD8, and CD20 were acquired (a total of 640 images). The number of pixels in each image matching a partition of Lab colour space corresponding to immunostained cells were counted using the ‘Color range’ and ‘Histogram’ tools in Adobe Photoshop 7. These pixel counts were converted to cell counts per mm2 using a calibration factor derived from one, two, three or all 10 images of each case/antibody combination. Results: Variations in the number of labelled pixels per immunostained cell made individual calibration for each case/antibody combination necessary. Calibration based on two fields containing the most labelled pixels gave a cell count minimally higher (+ 5.3%) than the count based on 10-field calibration, with 95% confidence limits − 14.7 to + 25.3%. As TIL density could vary up to 100-fold between cases, this accuracy and precision are acceptable. Conclusion: The methodology described offers sufficient accuracy, precision and efficiency to quantify the density of TIL sub-populations in breast cancer using commonly available software, and could be adapted to batch processing of image files

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care