To be able to apply the newest genetic analysis technologies in breast cancer research, enough DNA material must be available to perform this analysis. Often this is impossible with the minute amounts of tissue obtained via fine needle aspiration or laser capture microdissection currently the best methods available for removal of small amounts of tissue. Therefore whole genome-based DNA amplification techniques (e.g. PCR) are essential. The aim of this proposal was to evaluate a newly developed method, balanced PCR, which overcomes the difficulty of non-linear PCR-amplification of complex genomes and faithfully retains the difference among corresponding genes or gene fragments. In the three years of work we demonstrated the application of balanced PCR in performing genomic profiling of breast CA cell lines and samples (part of Tasks 2 and 3). In the second year we demonstrated the application of the method for gene expression profiling of breast CA cell lines (Task 1). This report describes the work conducted over the three years.
Genetic and gene expression profiling based diagnosis promises to refine (1) and potentially revolutionize (2) the existing cancer staging system and the management of early disease. Microarray-based gene expression profiling and Array-based Comparative Genomic Hybridization (array-CGH) offers global views of cancer genomes and transcriptomes by detecting amplification or deletion of cancer genes (3-10), whereas techniques like real time PCR (11) can be used for validation and quantification of the identified genomic changes.
Assesses the evidence that three marketed gene expression-based assays improve prognostic accuracy, treatment choice, and health outcomes in women diagnosed with early stage breast cancer. Three gene expression assays were evaluated; Oncotype DX¿, MammaPrint® and the Breast Cancer Profiling (BCP or H/I ratio) test, and for gene expression signatures underlying the assays. They sought evidence on: analytic performance of tests; clinical validity; clinical utility; harms; and impact on clinical decision making and health care costs. Conclusions: Oncotype DX is furthest along the validation pathway, with retrospective evidence that it predicts distant spread and chemotherapy benefit to a clinically relevant extent over standard predictors. Illus.
Based on cutting-edge research with more than 1,000 married couples, "Love Me Slender" shows you how to bolster your resolve by strengthening your relationship, offering a fresh approach to weight loss that will turn your spouse from diet saboteur into your most loyal health ally. Eat right. Stay active. Good health follows from a few simple habits, yet millions of us struggle every day to put these habits into practice. "Love Me Slender" offers new solutions based on a remarkable insight: The powerful connection we share with our mate can influence what we eat, how much we exercise, how well we age, and ultimately how long we live. Strengthening this connection, and using it to influence our daily habits, holds the key to better health. Over the course of their twenty-year collaboration, Drs. Thomas Bradbury and Benjamin Karney have witnessed how difficult it is for partners to give each other the support they both really need--especially around emotionally loaded topics like unhealthy eating habits and weight loss. As codirectors of the Relationship Institute at UCLA, they have analyzed hundreds of conversations between partners seeking to change their eating and exercise habits, and they have identified the specific principles that determine whether couples struggle--or succeed--in their quest to improve their health. Featuring case studies, self-assessments, and sound practical advice, "Love Me Slender" is an eye-opening, uplifting guide that shows relationship partners how to discover the right ways--and avoid the pitfalls--of supporting one another in their lifelong pursuit of better health.
"Breast cancer is a very heterogeneous disease. This heterogeneity can be observed at many levels, including gene expression, chromosomal aberrations, and disease pathology. A clear understanding of these differences is important since they impact upon treatment efficacy and clinical outcome. Recent studies have demonstrated that the tumour microenvironment also plays a critical role in cancer initiation and progression. Genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer, and have identified gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer-related pathways and processes. However, little work has been done in this context to examine the role of the tumour microenvironment in determining breast cancer outcome, or in defining breast cancer heterogeneity. Additionally, little is known about gene expression in histologically normal tissue adjacent to breast tumour, if this is influenced by the tumour, and how this compares with non-tumour-bearing breast tissue. By applying laser--capture microdissection and gene expression profiling to clinical breast cancer specimens the research presented in this thesis addresses these questions. We have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty. We determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumour-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumour tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favourable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression data set for comparative studies of tumour expression profiles. We compared gene expression profiles of tumour stroma from primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumour--derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node--negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumour progression. We show that gene expression in the breast tumour microenvironment is highly heterogeneous, identifying at least six different classes of tumour stroma with distinct expression patterns and distinct biological processes. Two of these classes recapitulate the processes identified in the stroma-derived prognostic predictor, while the others are new classes of stroma associated with distinct clinical outcomes. One of these is associated with matrix remodelling and is strongly associated with the basal molecular subtype of breast cancer. The remainder are independent of the previously published molecular subtypes of breast cancer. Additionally, based on independent data from over 800 tumors, the combinations of stroma classes and breast cancer subtypes identify new subgroups of breast tumors that show better discrimination between good and poor outcome individuals than the molecular breast cancer subtypes or the stroma classes alone, suggesting a novel classification scheme for breast cancer. This research demonstrates an important role for the tumour microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes suggesting new avenues for individualized treatment."--
Cancer is a multifaceted disease in which genetic changes induce uncontrolled tumor growth. Genomic characterization of cancer is now leading to better diagnostic, prognostic and predictive biomarkers, and effective individualized management. 'Fast Facts: Comprehensive Genomic Profiling' provides a crash course in the science, methods and application of genomic profiling. Assuming only the most basic knowledge – or memory – of cell biology, the authors provide an overview of DNA and RNA biology and next-generation sequencing. This sets in context the descriptions of prognostic and predictive biomarkers for different cancer types and genomic-based treatments. Finally, but importantly, some of the practicalities of gaining and interpreting genomic information are described. Whether you need a primer or a refresher, this short colorful book demystifies this complex subject. Contents: • Genetic mutations and biomarkers • Understanding next-generation sequencing • Elements of comprehensive genomic profiles • Role in precision oncology • Predictive and prognostic biomarkers • Overcoming barriers to genotype-directed therapy
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
