Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.

Implantation of a synthetic midurethral sling (SMUS) is the most commonly performed anti-incontinence operation in women worldwide. The effectiveness of the SMUS is comparable to that of the historical gold standards--autologous fascial slings and the Burch colposuspension. Much controversy, however, has evolved regarding the safety of this type of sling. Overall, the quality of the studies with respect to assessing risks of SMUS-associated complications is currently poor. The most common risks in patients with SMUS include urethral obstruction requiring surgery (2.3% of patients with SMUS), vaginal, bladder and/or urethral erosion requiring surgery (1.8%) and refractory chronic pain (4.1%); these data likely represent the minimum risks. In addition, the failure rate of SMUS implantation surgery is probably at least 5% in patients with stress urinary incontinence (SUI). Furthermore, at least one-third of patients undergoing sling excision surgery develop recurrent SUI. Considering the additional risks of refractory overactive bladder, fistulas and bowel perforations, among others, the overall risk of a negative outcome after SMUS implantation surgery is ≥15%.

BackgroundBreast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays.Methods and FindingsDifferential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment.ConclusionsUsing quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.