Population attributable fractions for ovarian cancer in Swedish women by morphological type

Using the Swedish Family-Cancer Database, among a total of 1 030 806 women followed from 1993 through 2004, invasive and borderline epithelial ovarian cancer was identified in 3306 and 822 women respectively, with data on family history, reproductive variables, residential region and socioeconomic status. Relative risks and population-attributable fractions (PAFs) were estimated by Poisson regression. The overall PAFs of invasive epithelial ovarian cancer for family history and for reproductive factors were 2.6 and 22.3%, respectively, for serous/seropapillary cystadenocarcinoma (3.0 and 19.1%), endometrioid carcinoma (2.6 and 26.6%), mucinous cystadenocarcinoma (0.5 and 23.9%) and clear-cell carcinoma (2.6 and 73.9%). The corresponding PAFs of borderline tumours due to family history were lower, but higher due to reproductive factors. Family history, low parity and young age at first birth were associated with elevated risks. The risks for women with a family history were among the highest, but these women accounted for the smallest proportion of the cases, giving the lowest PAFs

Socio-demographic and clinical characteristics of re-presentation to an Australian inner-city emergency department: implications for service delivery

BACKGROUND: People who have complex health care needs frequently access emergency departments for treatment of acute illness and injury. In particular, evidence suggests that those who are homeless, or suffer mental illness, or have a history of substance misuse, are often repeat users of emergency departments. The aim of this study was to describe the socio-demographic and clinical characteristics of emergency department re-presentations. Re-presentation was defined as a return visit to the same emergency department within 28 days of discharge from hospital. METHODS: A retrospective cohort study was conducted of emergency department presentations occurring over a 24-month period to an Australian inner-city hospital. Characteristics were examined for their influence on the binary outcome of re-presentation within 28 days of discharge using logistic regression with the variable patient fitted as a random effect. RESULTS: From 64,147 presentations to the emergency department the re-presentation rate was 18.0% (n = 11,559) of visits and 14.4% (5,894/40,942) of all patients. Median time to re-presentation was 6 days, with more than half occurring within one week of discharge (60.8%; n = 6,873), and more than three-quarters within two weeks (80.9%; n = 9,151). The odds of re-presentation increased three-fold for people who were homeless compared to those living in stable accommodation (adjusted OR 3.09; 95% CI, 2.83 to 3.36). Similarly, the odds of re-presentation were significantly higher for patients receiving a government pension compared to those who did not (adjusted OR 1.73; 95% CI, 1.63 to 1.84), patients who left part-way through treatment compared to those who completed treatment and were discharged home (adjusted OR 1.64; 95% CI, 1.36 to 1.99), and those discharged to a residential-care facility compared to those who were discharged home (adjusted OR 1.46: 95% CI, 1.03 to 2.06). CONCLUSION: Emergency department re-presentation rates cluster around one week after discharge and rapidly decrease thereafter. Housing status and being a recipient of a government pension are the most significant risk factors. Early identification and appropriate referrals for those patients who are at risk of emergency department re-presentation will assist in the development of targeted strategies to improve health service delivery to this vulnerable group

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies

Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users

A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer

BACKGROUND: Sequential biopsy of breast cancer is used to assess biomarker effects and drug efficacy. The preoperative "window of opportunity" setting is advantageous to test biomarker changes in response to therapeutic agents in previously untreated primary cancers. This study tested the consistency over time of paired, sequential biomarker measurements on primary, operable breast cancer in the absence of drug therapy. METHODS: Immunohistochemistry was performed for ER, PR and Ki67 on paired preoperative/operative tumor samples taken from untreated patients within 2 weeks of each other. Microarray analysis on mRNA extracted from formalin fixed paraffin embedded cores was performed using Affymetrix based arrays on paired core biopsies analysed using Ingenuity Pathway Analysis (IPA) and Gene Set Analysis (GSA). RESULTS: In 41 core/resection pairs, the recognised trend to lower ER, PR and Ki67 score on resected material was confirmed. Concordance for ER, PR and Ki67 without changing biomarker status (e.g. ER+ to ER-) was 90, 74 and 80 % respectively. However, in 23 paired core samples (diagnostic core v on table core), Ki67 using a cut off of 13.25 % was concordant in 22/23 (96 %) and differences in ER and PR immunohistochemistry by Allred or Quickscore between the pairs did not impact hormone receptor status. IPA and GSA demonstrated substantial gene expression changes between paired cores at the mRNA level, including reduced expression of ER pathway analysis on the second core, despite the absence of drug intervention. CONCLUSIONS: Sequential core biopsies of primary breast cancer (but not core versus resection) was consistent and is appropriate to assess the effects of drug therapy in vivo on ER, PR and Ki67 using immunohistochemistry. Conversely, studies utilising mRNA expression may require non-treatment controls to distinguish therapeutic from biopsy differences

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe