Author Interviews / 11.05.2020

MedicalResearch.com Interview with: David Spetzler, M.S., Ph.D., M.B.A. President and Chief Scientific Officer Caris Life Sciences MedicalResearch.com: What is the background for this announcement (WES)? Response: The announcement is about the launch of Caris’ latest molecular profiling test, called MI ExomeTM.  MI Exome a next-generation sequencing-based assay analyzing the whole exome of 22,000 DNA genes.  It is unique in that it will be run on every patient and will deliver unprecedented detail into the genomic characteristics of cancers, which will greatly improve our ability to understand cancer and provide insights needed to help physicians and patients make more informed treatment decisions that improve outcomes. (more…)
Author Interviews, Cancer Research, Genetic Research / 04.10.2019

MedicalResearch.com Interview with: Dr Ranjit Manchanda MD, MRCOG, PhD Professor & Consultant Gynaecological Oncologist NHS Innovation Accelerator (NIA) Fellow Integrated Academic Training Programme Director London Specialty School of Obstetrics & Gynaecology, Health Education England Cancer Research UK, Barts Centre | Queen Mary University of London Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital London  MedicalResearch.com: What is the background for this study? Response: Current national and international guidelines recommend genetic-testing (for BRCA genes) in women with breast cancer (BC) who fulfil recognised/established clinical criteria which are based on a history of cancer in the patient and family. However 50% of BRCA carriers do not fulfil these criteria. Thus the current  family-history or clinical-criteria based approach misses half the people at risk. Additionally only 20%-30% of patients eligible tend to get referred for and access BRCA testing. Newer genes like PALB2 which cause breast cancer have been identified and can also be tested for. Knowing a patient’s mutation status (carrier identification) can have a number of benefits. After unilateral breast cancer, mutations carriers can choose contralateral prophylactic-mastectomy (CPM) or preventative mastectomy of the second breast to reduce their risk of developing contralateral breast cancer. Additionally they can opt for surgical prevention for ovarian-cancer (OC). Cancer affected carriers may become eligible for novel drugs (like poly-adenosine-diphosphate-ribose-polymerase (PARP) inhibitors) and other precision-medicine based novel drug therapies through clinical trials. A major advantage of genetic-testing is enabling testing relatives of breast cancer mutation carriers, to identify unaffected relatives carrying mutations who can benefit from early diagnosis and cancer prevention. Testing everyone instead of being restricted by family history will identify many more mutation carriers and their family members who can benefit from precision prevention. A large proportion of these cancers are preventable in known unaffected mutations carriers. (more…)
Antibiotic Resistance, Author Interviews, Cancer Research, Genetic Research, Journal Clinical Oncology, University Texas / 03.10.2019

MedicalResearch.com Interview with: Fangjian Guo, MD, PhD Department of Obstetrics and Gynecology Center for Interdisciplinary Research in Women’s Health University of Texas Medical Branch Galveston TX  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The identification of BRCA1/BRCA2 pathogenic variants in women susceptible to breast or ovarian cancer in the 1990s created an opportunity for targeted, individualized cancer prevention. BRCA testing in young women before cancer onset enables early detection of those with increased cancer risk and creates an opportunity to offer life-saving prophylactic procedures and medication. We used insurance claims data to assess the use of BRCA testing in unaffected young women <40 years of age between 2006 and 2017 and found that BRCA testing among cancer-free women under 40 has more than doubled in recent years. However, only about 25% of all BRCA testing done in 2017 was performed in unaffected young women under 40. (more…)
Author Interviews, Genetic Research, OBGYNE / 18.02.2019

MedicalResearch.com Interview with: Zhiyong Zhang PhD Key Laboratory for the Physics and Chemistry of Nanodevices Department of Electronics Peking University Beijing China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Down syndrome is caused by the presence of an extra 21st chromosome within the genome and is the most common birth defect (occurring in approximately 1 in 800 births). In the absence of a multiplexed quantitative diagnostic device, pregnant women have been examined with the ultrasound and the indirect biochemical markers (Alpha-fetoprotein, chorionic gonadotropin and free estriol) which are accompanied with a high misdiagnosis rate. And the diagnostic test (such as amniocentesis) following the wrong screening test results will bring harm to both the pregnant women and the fetuses. Through PCR (polymerization chain reaction) amplification of the fetal DNA in the pregnant mother’s peripheral blood and fluorescence read-out, whole-genome sequencing (WGS)-based non-invasive prenatal testing (NIPT) sequences all the genomic DNA segments in parallel and quantitatively compares the percentage of different chromosomes, which increases the sensitivity for prenatal detection of Down syndrome. However, the complex instrumental setups and the resulted high processing cost present challenges for the large-scale application of WGS-based diagnosis at the point of care in the urban and rural areas of developing countries. Hence, beside the costly WGS method, there is an urgent need to develop a cost-effective NIPT biochip with simple instrumental setting, fast detection speed, high sensitivity, and programmable to multiple disease markers. Taking advantages of we have developed a novel field effect transistor (FET) based biosensor that reveals a fast, ultra-sensitive, highly specific and cost-effective methods and someday can be used to detect fetal Down syndrome in NIPT.  (more…)
Author Interviews, Columbia, Genetic Research, Kidney Disease / 03.01.2019

MedicalResearch.com Interview with: Emily E. Groopman, B.A Departments of Medicine Hammer Health Sciences, and the Department of Epidemiology Columbia University, New York MedicalResearch.com: What is the background for this study? Response: Exome sequencing (ES), targeted capture of the protein-coding segments of the human genome, is quickly becoming a first-line diagnostic tool in clinical medicine, particularly for pediatric disorders and cancer. However, the utility of ES has not been investigated for the majority of constitutional disorders in adults, including for chronic kidney disease (CKD), which collectively affects more than 1 in 10 individuals worldwide. Thus, we performed ES in 3,315 patients with CKD drawn from two independent cohorts, and evaluated the diagnostic yield and the clinical implications of genetic findings. The cohort was predominantly adult (91.6% of patients aged >21 years), ethnically diverse, and encompassed the major CKD subtypes, broadly reflective of the demographic and clinical features of United States CKD patient population. (more…)
Author Interviews, Genetic Research, Osteoporosis, PLoS, Stanford / 29.07.2018

MedicalResearch.com Interview with: Stuart Kim PhD Professor of Developmental Biology, Emeritus Bio-X Affiliated Faculty James H. Clark Center Stanford University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoporosis is caused by a reduction in bone mass, and leads to a high incidence of bone fracture because the weakened bone is less able to withstand the stress of slips and falls. Osteoporosis affects millions of elderly, is responsible for as many as 50% of fractures in women and 25% of fractures in men over the age of 50, and accounts for $19 billion in annual health care costs in the US. Identification of people with an increased genetic risk for osteoporosis could reduce the incidence of bone fracture. Low BMD is also a risk factor for stress fractures. For athletes and military personnel undergoing harsh rigors of training, stress fractures are common injuries that limit playing time, military effectiveness and competitive success. Using data from UK Biobank, a genome-wide association study identified 1,362 independent SNPs that clustered into 899 loci of which 613 are new. These data were used to train a genetic algorithm using 22,886 SNPs as well as height, age, weight and sex as predictors. Individuals with low genetic scores (about 2% of those tested) showed a 17-fold increase in risk for osteoporosis and about a 2-fold increase in risk of fractures. (more…)
Author Interviews, Breast Cancer, Genetic Research / 19.02.2018

MedicalResearch.com Interview with: Amanda Toland, PhD, Cancer biology and genetics researcher of The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Breast Information Core (or BIC) is a database that catalogs BRCA1 and BRCA2 sequenced variants.  The BIC is hosted by the National Human Genome Research Institute at NIH and has a steering committee that oversees the BIC and has members from Europe, the middle East, Australia and the US.  In BIC SC discussions, we learned that there are differences in how BRCA1/2 clinical is testing between countries. To characterize this variation, we performed an international survey of 86 genetic testing labs from around the world. Our main findings are that there were many variations between testing laboratories.  These include: technologies differed for finding “large” genetic sequence variants, what parts of the genes were assessed, how genetic variants were classified as disease associated or not being associated with diseases, if genetic sequencing information was shared in public databases and testing volume. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, JAMA / 15.12.2017

MedicalResearch.com Interview with: Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The recent debate on laboratory developed tests (LDTs) and FDA-approved companion diagnostics (FDA-CDs) has centered upon both the regulatory and performance aspects of LDTs and we, at the College of American Pathologists (CAP), had the data through our proficiency testing (PT) programs to address the latter point, performance that we wanted to share with the community.  We analyzed almost 7000 PT responses on three molecular oncology tests, those for BRAF, EGFR, and KRAS mutations, and found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall. The second key finding of the study was that more than 60% of all laboratories in our study that were using an FDA-CD kit report using it with modifications from the FDA-approved protocol.  These modifications in fact render these test LDTs.  These modifications appear to be driven by the exigencies of real day-to-day clinical practice that requires adapting the assays to meet the needs of a variety of clinical situations that may not be accommodated by the FDA-approved protocol.  These modifications include, for example, the testing of other tumor types that may carry targetable variants, different types of input specimen preparations available in pathology such as cytology smears or other fresh specimens rather than paraffin blocks, and availability of different methods of DNA quantification that those mandated by the FDA approval based upon pre-existing technologies in the laboratories.  In the clinical laboratory, we are always acutely aware that there is a patient awaiting this result. Therefore, we validate our assays to ensure that we can provide reliable and accurate results from our laboratory under as many varied clinical situations as possible. These data support that practice. (more…)
Author Interviews, Clots - Coagulation, Genetic Research, JAMA, Surgical Research / 04.10.2017

MedicalResearch.com Interview with: Anne R. Bass, MD Associate Professor of Clinical Medicine Weill Cornell Medical College Rheumatology Fellowship Program Director Hospital for Special Surgery New York, NY 10021 MedicalResearch.com: What is the background for this study? Response: Blood thinners are used after orthopedic surgery to prevent blood clots from forming in the legs and traveling to the lungs. They are also used in patients with certain heart diseases to prevent strokes. Blood thinners, like warfarin, are effective but can be associated with serious bleeding complications, especially if the wrong dose is given. Genetic testing can help doctors predict the right warfarin dose to use in an individual patient. In this trial, ≈1600 elderly patients undergoing hip or knee replacement were randomly assigned to receive warfarin dosing based on genetics plus clinical factors (like height, weight and gender), or based on clinical factors alone. The specific genes tested wereVKORC1, CYP2C9, and CYP4F2 which influence warfarin metabolism and the body’s ability to produce clotting factors. (more…)
Author Interviews, Breast Cancer, Genetic Research / 16.02.2017

MedicalResearch.com Interview with: Dr. med. Rachel Würstlein Senior Specialist Clinic and Polyclinic for Obstetrics and Gynecology Klinikum der Ludwig-Maximilians-Universität München • Campus Innenstadt Munich MedicalResearch.com: What is the background for this study? Response: Gene expression profiles provide important information on the risk of recurrence, and subtyping in HR+ HER2- early breast cancer, in addition to conventional clinicopathological factors. The PRIMe study was performed by the West German Study Group (WSG) and prospectively investigated the impact of the gene expression tests MammaPrint, a 70-Gene Breast Cancer Recurrence Assay, and the corresponding 80-Gene Molecular Subtyping Assay, BluePrint, on adjuvant chemotherapy decisions for early-stage breast cancer patients. To do this, a risk assessment (chemotherapy followed by endocrine therapy, versus endocrine therapy alone) for distant metastasis was performed in 452 patients from 27 study centers using conventional clinicopathological factors such as tumour size and grade first, then compared to the results of the gene expression tests MammaPrint and BluePrint. Doctors and patients then reviewed the results and made a decision on the optimal treatment plan, namely in deciding whether or not patients would benefit from, and should therefore be treated with adjuvant chemotherapy. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 17.12.2016

MedicalResearch.com Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH 43221 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was part of the Ohio Colorectal Cancer Prevention Initiative, a statewide study being conducted at 50 hospitals that includes universal tumor screening for Lynch syndrome. For the subset of 450 colorectal cancer patients diagnosed under age 50, we performed multi-gene cancer panel testing regardless of the results of their tumor screening for Lynch syndrome since early age of diagnosis is a red flag that a cancer might be hereditary. (more…)
Author Interviews, Genetic Research, OBGYNE / 08.04.2015

Jeanne M. Meck, PhD FACMG Director, Prenatal Diagnosis & Cytogenomic GeneDx Gaithersburg, MD 20877MedicalResearch.com Interview with: Jeanne M. Meck, PhD FACMG Director, Prenatal Diagnosis & Cytogenomic GeneDx Gaithersburg, MD 20877 Medical Research: What is the background for this study? Dr. Meck: Non-invasive prenatal screening (NIPS) for fetal aneuploidy is a new test which requires only a blood sample from the pregnant mother to provide a risk estimate of whether or not her fetus has a chromosomal aneuploidy such as trisomy 21 (Down syndrome), trisomies 13 or 18, or a sex chromosome abnormality. This testing relies on the fact that circulating maternal blood contains cell free fetal DNA. Published studies have reported very high specificities and sensitivities. However, the more important question is what is the positive predictive value (PPV= #true positive results/#true positive + false positive results) since it answers the question of interest to physicians and patients: “Given an Non-invasive prenatal screening result that shows a high risk for a given fetal aneuploidy, what is the chance that the fetus is affected?” We attempted to answer this question by looking at the results of fetal chromosome analyses on chorionic villus samples (CVS) or amniotic fluid that were referred to our cytogenetics laboratories after Non-invasive prenatal screening in order to see if NIPS correctly predicted the fetal karyotype. (more…)
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, University of Michigan / 06.04.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer.  Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations. (more…)
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA, Personalized Medicine / 05.03.2015

Dr. Michaela A. Dinan Ph.D Department of Medicine Duke UniversityMedicalResearch.com Interview with: Dr. Michaela A. Dinan Ph.D Department of Medicine Duke University Medical Research: What is the background for this study? What are the main findings? Dr. Dinan: We wanted to examine how  Oncotype DX® Breast Cancer Test (ODX) was being used in real-world practice at the population level. ODX has been examined in clinical trials and limited academic settings but we know that these patients are often younger, have fewer medical comorbidities, and do not necessarily accurately reflect the majority patients with cancer.  In our study, we observed that Oncotype DX® Breast Cancer Test was being used predominately in accordance with guidelines which recommend the test for women with estrogen-receptor positive, disease. We also looked just at women under the age of 70 who met guideline criteria for testing, because this population would include those women who were more likely to be chemotherapy candidates, and we saw a rapid uptake of the test between 2005 and 2009, with use of the test increasing from 8% to 39%. (more…)
Author Interviews, Breast Cancer, Genetic Research / 29.04.2014

Dr. Yvonne Bombard, PhD Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of TorontoMedicalResearch.com Interview with: Dr. Yvonne Bombard, PhD Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto MedicalResearch.com: What are the main findings of the study? Dr. Bombard: The main finding of the study is that gene expression profiling tests play a critical role when women with early-stage breast cancer decide whether to have chemotherapy, but many of them do not fully understand what some of the test results mean. For many the gene expression profiling test was the main factor in their treatment decision. The women we interviewed understood the test would indicate whether chemotherapy would be beneficial to them. But many thought the test reflected their unique circumstances and did not understand that their test result was based on larger population statistics. Patients often viewed their gene expression profiling results as providing information that was more scientifically valid, uniquely personalized and emotionally significant than any other information they had received. For many, the test was a transformational element that empowered them, allowed them to feel confident in their decisions and may even have rescued them from unnecessary chemotherapy. Patients described emotionally and socially complex reasons why they valued gene expression profiling testing in making their treatment decisions. Patients valued the test because it provided them with certainty amidst confusion, with options and a sense of empowerment, and with personalized, authoritative information. (more…)