Avoiding breast cancer surgery in a select cohort of complete responders to neoadjuvant chemotherapy: The long-term outcomes.

BACKGROUND: Lately, there has been a resurgence of interest in de-escalation of breast surgery in complete responders to neoadjuvant chemotherapy (NAC). Advanced cytotoxic & targeted therapies have improved tumour response.This study evaluates long-term outcomes of post-NAC breast cancer patients, in relation to their surgical management dictated by the NAC response. MATERIALS AND METHODS: Post-NAC breast cancer patients from January 2000 to December 2010 were divided into "No surgery", "WLE" and "Mastectomy" groups. ANOVA and Kaplan-Meier statistical analyses were used to compare overall survival (OS) and disease-free-survival (DFS) in these groups. RESULTS: This retrospective study included 121 patients with a long median follow-up of 11.5 years. At 10 years the OS was 66.10% and DFS was 59.82%. Complete NAC-responders did not undergo breast surgery but received radiotherapy. Patients were divided into No surgery (n = 28), WLE (n = 44), Mastectomy (n = 49) groups.Comparisons of OS and DFS between groups showed statistically significant differences (p = 0.0003, p = 0.0007 respectively). The no surgery group showed low local recurrence (7.14%). CONCLUSION: The observed slightly better long-term outcomes with low local recurrences in complete NAC-responders who did not undergo breast surgery but received radiotherapy could be linked to cautious response assessment and meticulous patient selection with early, biologically favourable breast cancer.Importance of PCR assessment cannot be underestimated if breast surgery were to be de-escalated or even omitted in complete NAC-responders.Considering the study limitations, avoiding surgery in all complete NAC-responders may still not be the preferred option. Future appropriate clinical trials with well-defined protocols may pave the way forward.

Using Zoo Welfare Assessments to Identify Common Issues in Developing Country Zoos.

Zoo animal welfare is a high priority for many institutions worldwide, with modern zoos now ensuring that animals are housed and cared for to the highest standards. However, in countries where this knowledge is not as available or understood, standards may be lower. The aim of this research was to investigate if there were common zoo welfare concerns across developing country zoos. Wild Welfare is a charity working globally to improve welfare for zoo animals and has an independent welfare audit that is carried out before any intervention occurs. The Wild Welfare Audit, consisting of 110 questions, covering nine topics, was completed at 11 zoos in seven developing countries (Brazil, Egypt, Libya, Indonesia, Thailand, Malaysia and Vietnam) following a Likert scale score (1-3). A principal component analysis was also performed to evaluate the audit questions. The results suggest that common areas of concern were animal behaviour, positive animal mental states and human health and safety. These themes were likely due to the lack knowledge and understanding that may be linked to historical and cultural differences. This research has helped to revise the welfare audit as well as inform future intervention strategies for improving developing country zoo animal welfare.

Mass spectrometry protein expression profiles in colorectal cancer tissue associated with clinico-pathological features of disease.

BACKGROUND: Studies of several tumour types have shown that expression profiling of cellular protein extracted from surgical tissue specimens by direct mass spectrometry analysis can accurately discriminate tumour from normal tissue and in some cases can sub-classify disease. We have evaluated the potential value of this approach to classify various clinico-pathological features in colorectal cancer by employing matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). METHODS: Protein extracts from 31 tumour and 33 normal mucosa specimens were purified, subjected to MALDI-Tof MS and then analysed using the 'GenePattern' suite of computational tools (Broad Institute, MIT, USA). Comparative Gene Marker Selection with either a t-test or a signal-to-noise ratio (SNR) test statistic was used to identify and rank differentially expressed marker peaks. The k-nearest neighbours algorithm was used to build classification models either using separate training and test datasets or else by using an iterative, 'leave-one-out' cross-validation method. RESULTS: 73 protein peaks in the mass range 1800-16000Da were differentially expressed in tumour verses adjacent normal mucosa tissue (P < or = 0.01, false discovery rate < or = 0.05). Unsupervised hierarchical cluster analysis classified most tumour and normal mucosa into distinct cluster groups. Supervised prediction correctly classified the tumour/normal mucosa status of specimens in an independent test spectra dataset with 100% sensitivity and specificity (95% confidence interval: 67.9-99.2%). Supervised prediction using 'leave-one-out' cross validation algorithms for tumour spectra correctly classified 10/13 poorly differentiated and 16/18 well/moderately differentiated tumours (P = < 0.001; receiver-operator characteristics - ROC - error, 0.171); disease recurrence was correctly predicted in 5/6 cases and disease-free survival (median follow-up time, 25 months) was correctly predicted in 22/23 cases (P = < 0.001; ROC error, 0.105). A similar analysis of normal mucosa spectra correctly predicted 11/14 patients with, and 15/19 patients without lymph node involvement (P = 0.001; ROC error, 0.212). CONCLUSIONS: Protein expression profiling of surgically resected CRC tissue extracts by MALDI-TOF MS has potential value in studies aimed at improved molecular classification of this disease. Further studies, with longer follow-up times and larger patient cohorts, that would permit independent validation of supervised classification models, would be required to confirm the predictive value of tumour spectra for disease recurrence/patient survival.

Analysis of post-operative changes in serum protein expression profiles from colorectal cancer patients by MALDI-TOF mass spectrometry: a pilot methodological study.

BACKGROUND: Mass spectrometry-based protein expression profiling of blood sera can be used to discriminate colorectal cancer (CRC) patients from unaffected individuals. In a pilot methodological study, we have evaluated the changes in protein expression profiles of sera from CRC patients that occur following surgery to establish the potential of this approach for monitoring post-surgical response and possible early prediction of disease recurrence. METHODS: In this initial pilot study, serum specimens from 11 cancer patients taken immediately prior to surgery and at approximately 6 weeks following surgery were analysed alongside 10 normal control sera by matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). Using a two-sided t-test the top 20 ranked protein peaks that discriminate normal from pre-operative sera were identified. These were used to classify post-operative sera by hierarchical clustering analysis (Spearman's Rank correlation) and, as an independent 'test' dataset, by k-nearest neighbour and weighted voting supervised learning algorithms. RESULTS: Hierarchical cluster analysis classified post-operative sera from all six early Dukes' stage (A and B) patients as normal. The remaining five post-operative sera from more advanced Dukes' stages (C1 and C2) were classified as cancer. Analysis by supervised learning algorithms similarly grouped all advanced Dukes' stages as cancer, with four of the six post-operative sera from early Dukes' stages being classified as normal (P = 0.045; Fisher's exact test). CONCLUSIONS: The results of this pilot methodological study illustrate the proof-of-concept of using protein expression profiling of post-surgical blood sera from individual patients to monitor disease course. Further validation on a larger patient cohort and using an independent post-operative sera dataset would be required to evaluate the potential clinical relevance of this approach. Prospective data, including follow-up on patient survival, could in the future, then be evaluated to inform decisions on individualised treatment modalities.

Case report: Metaplastic carcinoma presenting as a breast abscess.

Metaplastic breast carcinoma (MBC) is a rare neoplasm containing a mixture of epithelial and mesenchymal elements. The epithelial component is usually ductal carcinoma but may include other variants of breast carcinomas including squamous carcinoma and osteogenic sarcoma. There is a relative paucity of data regarding such tumours. Metaplastic carcinoma carries a prognosis not dissimilar to that of comparable ductal carcinoma. This is the case of a 57 year old patient with MBC presenting with a breast abscess. A thorough literature search has not revealed any previous reports of MBC presenting as a breast abscess.