Resection rate, hospital procedure volume and survival in pancreatic cancer patients in England:Population-based study, 2005-2009

Objective: We assessed the association between population resection rates, hospital procedure volume and death rates in pancreatic cancer patients in England. Design: Patients diagnosed with pancreatic cancer were identified from a linked cancer registration and Hospital Episode Statistics dataset. Cox regression analyses were used to assess all-cause mortality according to resection quintile and hospital volume, adjusting for sex, age, deprivation and comorbidity. Results: There were 31,973 pancreatic cancer patients studied, 2580 had surgery. Increasing resection rates were associated with lower mortality among all patients (chi(2)(1df) = 176.18, p(trend) < 0.001), with an unadjusted hazard ratio (HR) of 0.78 95%CI [0.75 to 0.81] in the highest versus the lowest resection quintile. Adjustment changed the estimate slightly (HR 0.82, 95%CI [0.79 to 0.85], (chi(2)(1df) = 99.44, P-trend < 0.001)). Among patients that underwent surgery, higher procedure volume was associated with lower mortality (HR = 0.88 95%CI [0.75-1.03] in hospitals carrying out 30+ versus <15 operations a year, shared frailty model, chi(2)(1df) = 1.82, P-trend = 0.177). Conclusion: Higher population resection rates were associated with lower mortality. The association with hospital procedure volume was less clear possibly due to small number of patients who underwent surgery. Nevertheless these results suggest survival is higher in hospitals that carry out a greater number of operations a year, particularly those doing 30+ operations, supporting the benefit of centralising peri-operative expertise in specialist centres. Ensuring people are increasingly diagnosed when they are suitable candidates for surgery, and have access to these specialist centres may lead to an increase in the proportion of patients that undergo surgical resection which could plausibly increase survival of pancreatic cancer patients. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved

Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines

Breast cancer has for long been recognized as a highly diverse tumor group, but the underlying genetic basis has been elusive. Here, we report an extensive molecular characterization of a collection of 41 human breast cancer cell lines. Protein and gene expression analyses indicated that the collection of breast cancer cell lines has retained most, if not all, molecular characteristics that are typical for clinical breast cancers. Gene mutation analyses identified 146 oncogenic mutations among 27 well-known cancer genes, amounting to an average of 3.6 mutations per cell line. Mutations in genes from the p53, RB and PI3K tumor suppressor pathways were widespread among all breast cancer cell lines. Most important, we have identified two gene mutation profiles that are specifically associated with luminal-type and basal-type breast cancer cell lines. The luminal mutation profile involved E-cadherin and MAP2K4 gene mutations and amplifications of Cyclin D1, ERBB2 and HDM2, whereas the basal mutation profile involved BRCA1, RB1, RAS and BRAF gene mutations and deletions of p16 and p14ARF. These subtype-specific gene mutation profiles constitute a genetic basis for the heterogeneity observed among human breast cancers, providing clues for their underlying biology and providing guidance for targeted pharmacogenetic intervention in breast cancer patients