Most Laboratory Testing For Cancer-Causing Gene Mutations Found Reliable

MedicalResearch.com Interview with:

Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115

Dr. Kim

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.

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Genetic Testing Reduces Risk Of Side Effects From Anticoagulation After Surgery

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

Dr. Bass

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.

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Mammaprint Profiling Improves Breast Cancer Adjuvant Treatment Decisions

MedicalResearch.com Interview with:

Dr. med. Rachel Würstlein</strong> Senior Specialist Clinic and Polyclinic for Obstetrics and Gynecology Klinikum der Ludwig-Maximilians-Universität München • Campus Innenstadt Munich

Dr. Rachel Wuerstlein

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.

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Cancer Susceptibility Genes Common In Early-Onset Colorectal Cancer

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

Heather Hampel

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.

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Prenatal Blood Tests For Down Syndrome Good But Not Perfect

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.

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Many Women With Breast Cancer Want to Discuss Genetic Testing

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.

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Study Examines Use Of Oncotype DX® Breast Cancer Test In Medicare Patients

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, node negative 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%.

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Many Breast Cancer Patients Do Not Understand Gene Expression Profiling

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.

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