Author Interviews, Breast Cancer, JAMA, Mediterranean Diet / 14.09.2015

MedicalResearch.com Interview with: Miguel Ángel Martínez González MD Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid IdiSNA, Navarra Institute for Health Research, Pamplona, Navarra, Spain Medical Research: What is the background for this study? Response: ​Several observational studies and mechanistic experiments in animal models and cell lines suggested that the Mediterranean diet and minor components of extra-virgin olive oil may reduce the risk of developing breast cancer. The PREDIMED study was a randomized primary prevention trial for cardiovascular disease among high risk patients initially free of cardiovascular disease. The participants were 7,447 men and women (60-80 years old). We have used the data from women in this trial to assess the effect of the randomized diets on the occurrence of new cases of breast cancer. Medical Research: What are the main findings? Response: Among 4,152 women randomized to 3 different diets (1.- Mediterranean diet with free provision of extra-virgin​ olive oil; 2.- Mediterranean diet with free provision of tree nuts; and 3.- Advice to follow a low-fat diet, i.e. control group) We confirmed 35 new cases of invasive breast cancer during 4.8 of follow-up. A statistically significant 68% relative reduction in the risk of breast cancer in the Mediterranean diet with free provision of extra-virgin​ olive oil versus the control group was found. There was a significant trend of risk reduction associated with progressive increments in the intake of extra-virgin olive oil during the trial (with repeated yearly measurements of diet) when the 3 groups were assessed together.
Author Interviews, Pancreatic, Stem Cells / 14.09.2015

Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London EC1M 6BQMedicalResearch.com Interview with: Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London Medical Research: What is the background for this study? What are the main findings? Dr. Sancho: Cancer cells commonly rely on glycolysis, the type of metabolism that does not use oxygen to generate their energy however, we have now found that not all cancer cells are alike when it comes to metabolism. Pancreatic Cancer Stem cells (PancCSCs) can make use of a more efficient form of metabolism, called oxidative phosphorylation or OXPHOS, which does use oxygen. OXPHOS uses a part of the cell called mitochondria and it is this which can be targeted with anti-diabetic drug, metformin. Some PancSCs are however able to escape this treatment by being much more flexible in their metabolism, leading to a recurrence of the cancer, but we also found a way to prevent such resistance and force all Pancreatic Cancer Stem cells to keep using OXPHOS.
Author Interviews, Mayo Clinic, Thyroid / 09.09.2015

Juan P. Brito Campana, MBBS Division of Diabetes, Endocrinology, Metabolism, and Nutrition, Department of Medicine Mayo Clinic , Rochester, MinnesotaMedicalResearch.com Interview with: Juan P. Brito Campana, MBBS Division of Diabetes, Endocrinology, Metabolism, and Nutrition, Department of Medicine Mayo Clinic , Rochester, Minnesota Medical Research: What is the background for this study? Dr. Brito: The occurrence of thyroid cancer is increasing faster than any other cancer in the United States. If this trend continues, thyroid cancer will become the third most frequent cancer in women in the next five years. Despite this increase, death related to thyroid cancer has not increased.  The reason is that the majority of the new cases of thyroid cancer are small papillary thyroid cancers. These cancers are the most benign variant of thyroid cancer and most patients diagnosed with this type of cancer never experience any symptoms or other negative effects. To better understand how these new cases of thyroid cancer are diagnosed we studied every case of thyroid cancer diagnosed in Olmsted, County, MN from 1935-2012. Medical Research: What are the main findings? Dr. Brito: We found that almost half the new cases of thyroid cancer were found among people who did not have any symptoms related to thyroid cancer. The most frequent reasons for identifying these patients presenting were review of thyroid tissue removed for benign conditions; incidental discovery during an imaging test ; and investigations of patients with symptoms or palpable nodules that were clearly not associated with thyroid cancer, but triggered the use of imaging tests of the neck.
Author Interviews, Breast Cancer, Genetic Research, UCSF / 04.09.2015

Dr. Elisa Long PhD Assistant professor UCLA Anderson School of ManagementMedicalResearch.com Interview with: Dr. Elisa Long PhD Assistant professor UCLA Anderson School of Management Medical Research: What is the background for this study? What are the main findings? Dr. Long: The study was motivated by my own diagnosis of triple-negative breast cancer last year, at the age of 33. I also learned that I carried a BRCA1 mutation, despite no family history. As a patient, I would have benefitted tremendously from a universal BRCA screening program, but as a health services researcher, I had to ask if indiscriminate screening of all women in the U.S.—where only 1 in 400 carry a mutation—is a good use of resources. Using a previously published decision analytic model, we calculated the cost-effectiveness of universal BRCA screening. We find that compared to screening based on family history, it is not cost-effective, assuming a test price of $2,000 to $4,000. However, as the price of genetic testing continues to fall, as indicated by the $249 test now offered by Color Genomics, universal BRCA screening becomes much more affordable. Additionally, population screening of Ashkenazi Jewish women—among whom 1 in 50 carry a BRCA mutation—is very cost-effective, because the chances of finding a carrier are much higher.
Author Interviews, Chemotherapy, Genetic Research, Melanoma / 04.09.2015

Rutao Cui M. D., Ph. D. Vice Chair, Professor, Department of Pharmacology and Experimental Therapeutic Associate Professor of Pharmacology and Dermatology, and Member The Cancer Center Director The Laboratory of Skin Cancer Therapeutics (LSCT) Boston UniversityMedicalResearch.com Interview with: Rutao Cui M. D., Ph. D.  Vice Chair, Professor Department of Pharmacology and Experimental Therapeutic Associate Professor of Pharmacology and Dermatology, and Member The Cancer Center Director The Laboratory of Skin Cancer Therapeutics (LSCT) Boston University Medical Research: What is the background for this study? What are the main findings? Dr. Cui: Recent studies have revealed that the APC/CCdh1 E3 ubiquitin ligase may function as a tumor suppressor. However, the tumor suppressor role of APC/CCdh1 in melanoma remains largely unclear. Here, we report sporadic mutations occurring in APC components, including Cdh1 in human melanoma samples and that loss of APC/CCdh1 may predispose human melanomagenesis.
Author Interviews, Dermatology, JAMA, Melanoma / 03.09.2015

Simone Ribero, M.D., Ph.D. University of Turin Department of Medical Sciences Turin Italy and King’s College London Department of Twin Research and Genetic Epidemiology St Thomas’ campus London, UKMedicalResearch.com Interview with: Simone Ribero,  M.D., Ph.D.  University of Turin Department of Medical Sciences Turin Italy and King’s College London Department of Twin Research and Genetic Epidemiology St Thomas’ campus London, UK Medical Research: What is the background for this study? What are the main findings? Response: The histologic regression is a discussed feature and its prognostic role is debated in literature. Our group has previously described a favorable prognostic role of histological regression in stage I-II melanoma patients. Some clinicians still perform Sentinel Lymph Node biopsy on the basis of regression in thin melanoma considering this feature as able to underestimate Breslow Thickness. In this study we described in a metanalyses with more then 10000 melanoma patients that histological regression is inversely associated with Sentinel Lymph Node positivity.
Author Interviews, Biomarkers, Cancer Research / 03.09.2015

Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY MedicalResearch.com Interview with: Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY     Medical Research: What is the background for this study? What are the main findings? Dr. Shroyer: Patients that appear to have the same type of cancer often respond very differently to treatment; while some patients appear to go into long-term regression or are cured, others follow a rapid downhill course and ultimately die of their disease. This suggests that there are fundamental differences between tumors at the biologic level that are not detected by current clinical measures. In this study, we report the unexpected finding that cancer patients that have high levels of a protein called Keratin 17 (K17) have decreased long-term survival when compared to patients that express little to no K17 in their tumors. In addition, we found that K17 enters the nucleus of tumor cells to mediate the degradation of the master regulator of cell division and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17 increases the resistance of tumor cells to chemotherapy. These are critical findings because this is the first report that a keratin is an oncoprotein that can enter the nucleus to promote the development of cancer and resistance to chemotherapy.
Author Interviews, Cancer Research, Melatonin, Sleep Disorders / 03.09.2015

MedicalResearch.com Interview with: Charlotte Lund Rasmussen Research Unit, Department of Palliative Medicine Bispebjerg Hospital, Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Response: We see that patients with advanced cancer often suffer from fatigue, pain, depression, insomnia and other symptoms, which can have a profound impact on quality of life. Melatonin is a neurohormone and its secretion is closely tied to the circadian rhythm making it a regulator of the sleep-cycle. Studies have shown that cancer patients have lower levels of melatonin than healthy controls, which may contribute to their fatigue and lowered quality of life. Furthermore, previous studies have found a possible effect of melatonin in cancer therapy, and non-clinical trials have shown melatonin to inhibit cell division in tumors. To our knowledge, no trials to date have investigated the effects of melatonin on fatigue. Given the role of melatonin in the sleep cycle, the lowered levels of melatonin noted among cancer patients, and results from previous studies, we wanted to investigate melatonin’s effect on fatigue among patients with advanced cancer. The primary objective of our study was to determine whether oral melatonin administered at night would reduce physical fatigue in patients with advanced cancer who were being treated in a palliative care facility. The effect of melatonin on other cancer-related symptoms including mental fatigue, insomnia, pain, emotional function, loss of appetite, and overall QoL were also investigated. In this trial we tested a dose of 20 mg of melatonin taken orally at night. However, melatonin did not improve physical fatigue in patients with advanced cancer. Furthermore, we were unable to identify improvements in any other cancer-related symptoms.
Author Interviews, Cancer Research, Genetic Research / 02.09.2015

Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology, College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State UniversityMedicalResearch.com Interview with: Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Roychowdhury: Precision cancer medicine is a new paradigm to match patients to therapies based on the molecular alterations in their cancer. Novel genomic testing of cancer using next generation sequencing can reveal numerous mutations for each patient across many genes and types of cancer, and this requires detailed time-intensive interpretation. Driver mutations can confer a selective growth or survival advantage to cancer cells, while passenger mutations do not. Cancer Driver Log, or CanDL, is meant to aid interpretation of mutations by providing the latest literature evidence for individual driver mutations, and thereby aiding pathologists, lab directors, and oncologists in interpreting mutations found in their patient’s cancer.
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research / 02.09.2015

Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C. Medicalresearch.com Interview with: Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C.   MedicalResearch: What is the background for this study? What are the main findings? Dr. Packer: The background is that medulloblastoma is the most common childhood malignant brain tumor. It carries with it a variable prognosis. For some subsets of patients, with current available treatment which includes surgery, radiation and chemotherapy, we see survival rates as high as 90% (and often cures) 5 years following diagnosis and treatment. However, for some subsets of patients, survival rates are much poorer, in those with higher risk characteristics as low as 40% at 5 years. Current treatment also carries with it a significant risk for long term sequelae, including intellectual loss secondary to radiation therapy and persistent, at times devastating neurologic complications such as unsteadiness. To try to improve our understanding and ultimately our therapy for medulloblastoma, an international working group has shared patient specimens and patient information to attempt to determine what the molecular predictors of outcome are for children with medulloblastoma and if such molecular genetic findings can be used to develop better, safer therapies. Children’s National is part of this international collective of institutions, which published this and other studies. The main findings of this study are that complex, integrated genetic analysis of tumor specimens can be used to better understand and set the scene for better treatment of medulloblastoma.  Medulloblastoma can be broken into relatively distinct, molecular subtypes each with its own prognosis and potential therapy. A major finding of this study was that within a given tumor, different areas showed the same molecular genetic pattern. The importance of this is that since the tumors are relatively the same in different areas, molecularly-targeted therapies have an excellent chance of working on the entire tumor, resulting in better tumor control and safer treatments.
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Surgical Research / 01.09.2015

Dr. Rachel A Freedman MD MPH Assistant Professor of Medicine Harvard Medical SchoolMedicalResearch.com Interview with: Dr. Rachel A Freedman MD MPH Dana-Farber Cancer Institute Assistant Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Despite a lack of medical benefit for most patients, the rates for bilateral mastectomy (double mastectomy) are on the rise in the U.S. Many factors have been cited as potential reasons for this increase, such as one’s race/ethnicity, education level, family history, and use of MRI. Cancer stage has not consistently been a factor in past studies. In this study, we surveyed 487 women who were treated for breast cancer in Northern California within the California Cancer Registry, we examined factors associated with the type of surgery a woman received. In our study, we found strong associations for stage III cancer with receipt of unilateral and bilateral mastectomy. In addition, higher (vs. lower) income and older age were associated with lower odds of having bilateral surgery.
Author Interviews, Breast Cancer, NIH, Weight Research / 31.08.2015

Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health ScienceMedicalResearch.com Interview with: Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health Science MedicalResearch: What is the background for this study? Dr. White: Many studies have shown that being overweight or obese is a risk factor for postmenopausal breast cancer. We know less about how obesity impacts breast cancer risk in premenopausal women. About a third of U.S. adults are obese, which is defined as having a body mass index (BMI) greater than 30. Similarly, the prevalence of abdominal obesity, measured by a person’s waist circumference, has increased by 10% in the last decade. In 2012, more than two-thirds of U.S. women had a waist circumference that indicated abdominal obesity. Abdominal obesity may be a better predictor than BMI for breast cancer risk and other chronic diseases, because it is related to insulin resistance and can reflect metabolically active fat stores. In order to understand how different types of obesity (overall vs. abdominal) influence breast cancer risk, we used information from >50,000 participants in the Sister Study. The Sister Study, led by scientists at the National Institute of Environmental Health Sciences, part of the National Institutes of Health investigates environmental and genetic risk factors for breast cancer.
Author Interviews, Biomarkers, Pancreatic / 28.08.2015

Jenny Permuth Wey, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Cente MedicalResearch.com Interview with: Jenny Permuth Wey, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Center   Medical Research: What is the background for this study? What are the main findings? Dr. Wey: Pancreatic cancer is one of the deadliest cancers world-wide. It is currently the fourth leading cause of cancer-related deaths in the United States, and is predicted to become the second leading cause by 2030. Currently there are no accurate methods to diagnose pancreatic cancer early when a patient may be eligible for surgery to remove the tumor and hopefully survive longer. To beat this disease, early detection is key, and our team has dedicated efforts to studying pancreatic cancer in its ‘precancerous’ state because we and other researchers believe that the identification and treatment of precancerous pancreatic lesions offers a promising strategy to reduce the number of people losing their lives to this disease. Similar to how colon polyps can progress into colon cancer, we now know that certain types of pancreatic cystic lesions can progress into pancreatic cancer. Pancreatic cancer precursors/pre-cancers known as intraductal papillary mucinous neoplasms (IPMNs) account for nearly one-half of the estimated 150,000 asymptomatic pancreatic cysts detected as ‘incidental findings’ on computed tomography (CT) scans or magnetic resonance imaging (MRI) scans each year during the clinical work-up for an unrelated condition.  Imaging alone cannot reliably distinguish between benign, pre-cancerous, and cancerous cysts, and cannot differentiate ‘low-risk’intraductal papillary mucinous neoplasms' (defined as low- or moderate-grade disease) that can be monitored from ‘high-risk’ IPMNs (defined as high-grade or invasive disease) that should be surgically removed.  The decision to undergo pancreatic surgery is not trivial for the patient and medical team since pancreatic surgery can be associated with an estimated 40% chance of complications and a 4% chance of death. Noninvasive tests are needed to accurately detect precancerous lesions of the pancreas so that personalized risk assessment and care can be provided. microRNAs (miRNAs) are small molecules that act as ‘master-regulators’ of cancer-related processes in the body. One of the main purposes of our ‘proof of principle’ study was to measure miRNAs in the blood and determine whether a set of miRNAs could distinguish patients with IPMNs from healthy individuals. We then sought to determine whether a set of miRNAs could distinguish patients known to have ‘low-risk’ IPMNs from those with ‘high-risk’ IPMNs.  We show that new, relatively inexpensive digital technology could reliably measure miRNAs in blood plasma (the pale yellow liquid component of blood) from individuals newly-diagnosed with pancreatic cancer precursors (IPMNs) and healthy individuals.  Thirty miRNAs out of 800 tested showed higher levels in IPMN patients compared to healthy individuals, providing a preliminary ‘miRNA signature’ that may be found only in people with early pancreatic disease, suggesting it could serve as an early diagnostic tool.  Furthermore, we also provide preliminary data to suggest that a 5-miRNA signature can partially distinguish high-risk IPMNs that warrant resection from low-risk IPMNs that can be watched.  This is important clinically because it would be opportune to personalize care such that high-risk IPMNs that warrant resection are properly identified while individuals with low-risk IPMNs are spared the substantial  risks of mortality and morbidity associated with overtreatment from unnecessary surgery.
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 27.08.2015

Michaela Ann Dinan Ph.D. Assistant Professor in Medicine Member of Duke Cancer Institute Duke University School of MedicinMedicalResearch.com Interview with: Michaela Ann Dinan Ph.D. Assistant Professor in Medicine Member of Duke Cancer Institute Duke University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Dinan: For many years we have known that overall, women with early stage, hormone receptor positive breast cancer show an overall survival benefit from the receipt of adjuvant chemotherapy.  However, depending on the age of the patient, we have also known that between 3 to 10% of patients appear to be truly experiencing this survival benefit and that we are treating a lot of women unnecessarily.  The use of the Oncotype DX assay has provided additional information for patients to assess who at low risk of disease progression and can forgo chemotherapy. In this study we looked to see whether the adoption of this assay was associated with reduce rates of chemotherapy in women over the age of 65.  We found that somewhat surprisingly, there was no overall association with receipt of the assay and use of chemotherapy.  However, in women who had high risk disease, receipt of the assay was associated with reduced rates of chemotherapy use.  In patients with low risk disease, receipt of the assay was associated with increased chemotherapy use.
Author Interviews, Cancer Research, Pain Research / 27.08.2015

Dr. Sebastiano Mercadante MD Director, Anesthesia and Intensive Care Unit and Pain Relief and Palliative Care Unit La Maddalena Cancer Center, Palermo, ItalyMedicalResearch.com Interview with: Dr. Sebastiano Mercadante MD Director, Anesthesia and Intensive Care Unit and Pain Relief and Palliative Care Unit La Maddalena Cancer Center, Palermo, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Mercadante:  Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background (1). Breakthrough cancer pain is a common problem in patients with cancer and is associated with significant morbidity. In a recent report in which a pragmatic definition of breakthrough cancer pain was used (2), the prevalence of BTcP was 75% (3). Oral morphine (OM) has been traditionally offered as a breakthrough cancer pain medication in doses of about 1/6 of the daily opioid regimen for years, although this approach has never been supported by any evidence. Different technologies have been developed to provide a rapid onset of effect with potent opioid drugs such as fentanyl (rapid onset opioids, ROOs) delivered by non-invasive routes. Fentanyl products have been shown to be significantly superior to oral opioids, but it has been suggested that the dose of fentanyl should be individually titrated in order to enable effective analgesia to be delivered while minimizing the risk of clinically significant adverse effects. The need of dose titration with rapid onset opioids has never been appropriately assessed and this statement is derived by a series of weaknesses of papers published for regulatory issues. Indeed, the only existing study comparing dose titration and proportional doses, reported that proportional doses of (Fentanyl buccal tablet) FBT are more effective and safe over dose titration method. NICE guidelines did not provide evidence for that, at least at certain time intervals after administration. To scientifically compare rapid onset opioids and oral morphine, we used a similar approach and made a strict selection of patients, according to a more specific algorithm for a diagnosis o fbreakthrough cancer pain. Thus, patients were randomized to receive in a crossover design Fentanyl buccal tablet and oral morphine, both given in doses proportional to opioid daily doses, for the management of breakthrough cancer pain. This comparative study has shown that, when giving the drugs for breakthrough cancer pain in doses proportional to the opioid regimen for background pain, Fentanyl was clearly superior for efficacy and rapidity in comparison with oral morphine. The analgesic effect was more intense either at 15 and 30 minutes after study medications were given. A larger number of episodes treated with Fentanyl buccal tablet  presented a decrease in pain intensity of ≥33% and ≥50% in comparison with episodes treated with oral morphine, and a relevant difference in SPID30 was reported. Of interest, adverse effects commonly observed in patients receiving opioids were not severe and did not differ between the treatments, suggesting that the use of proportional doses of both drugs are safe, reflecting what is derived by the long-lasting experience with oral morphine.  
Author Interviews, Breast Cancer, Genetic Research, Race/Ethnic Diversity / 26.08.2015

Tuya Pal MD Division of Population Sciences Department of Health Outcomes and Behavior Moffitt Cancer Center Tampa, Florida MedicalResearch.com Interview with: Tuya Pal MD Division of Population Sciences Department of Health Outcomes and Behavior Moffitt Cancer Center Tampa, Florida   Medical Research: What is the background for this study? Dr. Pal:  Young Black women bear a disproportionate burden associated with breast cancer incidence and mortality compared to their White counterparts. Given that inherited mutations in the BRCA1 and BRCA2 genes are more common among young breast cancer survivors, we questioned to what extent mutations in these genes might contribute to the racial disparity in breast cancer incidence among young women. Medical Research: What are the main findings? Dr. Pal:  Through conducting the largest U.S. based study of BRCA mutation frequency in young black women diagnosed with breast cancer at or below age 50, we discovered they have a much higher BRCA mutation frequency than that previously reported among young white women with breast cancer.  Specifically, of the 396 Black women with breast cancer diagnosed at or below age 50, 12.4% had mutations in either BRCA1 or BRCA2.  Furthermore, over 40 percent of those with a mutation had no close relatives with breast or ovarian cancer, which suggests that family history alone may not identify those at risk for carrying a BRCA mutation. 
Author Interviews, Chemotherapy, Journal Clinical Oncology / 25.08.2015

Anna Lin, MBA, PHD Senior Epidemiologist, Health Services Research American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303MedicalResearch.com Interview with: Anna Lin, MBA, PHD Senior Epidemiologist, Health Services Research American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 Medical Research: What is the background for this study? Dr. Lin: Evidence-based guidelines recommend the use of adjuvant chemotherapy in patients with Stage III colon cancer within 90 days of colectomy to improve disease-free and overall survival; however, a substantial proportion of patients do not receive this treatment.  Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. Medical Research: What are the main findings? Dr. Lin: The main findings of this study indicate that patients traveling more than 50 miles were less likely to receive adjuvant chemotherapy for Stage III node-positive colon cancer.  In addition, patients who had either no insurance or public (non-private) insurance and resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy.
Annals Internal Medicine, Author Interviews, Colon Cancer / 25.08.2015

Søren Friis, Senior Scientist, Associate Professor, MD Danish Cancer Society Research Center Danish Cancer Society Department of Public Health University of Copenhagen Faculty of Health Institute of Clinical Medicine Department of Clinical Epidemiology Aarhus University DenmarkMedicalResearch.com Interview with: Søren Friis, Senior Scientist, Associate Professor, MD Danish Cancer Society Research Center Danish Cancer Society Department of Public Health University of Copenhagen Faculty of Health Institute of Clinical Medicine Department of Clinical Epidemiology Aarhus University Denmark Medical Research: What is the background for this study? Dr. Friis: Although laboratory, clinical, and epidemiological studies have all provided strong evidence for protection against colorectal cancer from regular use of aspirin, the optimal dose and duration of use for cancer prevention remain to be established. Medical Research: What are the main findings? Dr. Friis: Continuous use of low-dose aspirin for five or more years was associated with a reduced risk of colorectal cancer, but overall long-term use (continuous or non-continuous) was not. Long-term, high-intensity use (average of ≥0.3 daily doses) of non-aspirin NSAIDs was associated with a substantially reduced risk of colorectal cancer, particularly for NSAIDs with the highest COX-2 selectivity. The results for long-term continuous users of low-dose aspirin should be interpreted cautiously, since these patients comprised only a small proportion of the low-dose aspirin users and might have a risk profile different from that of the general population.
Author Interviews, Baylor College of Medicine Houston, Cancer Research, Electronic Records, Journal Clinical Oncology / 25.08.2015

Hardeep Singh, MD MPH Chief, Health Policy, Quality and Informatics Program, Houston Veterans Affairs Health Services Research Center for Innovations Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine Houston TX 77030 MedicalResearch.com Interview with: Hardeep Singh, MD MPH Chief, Health Policy, Quality and Informatics Program, Houston Veterans Affairs Health Services Research Center for Innovations Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine Houston TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Singh: Missed or delayed diagnoses are among the most common patient safety concerns in outpatient settings, and measuring and reducing them is a high priority. Our computerized triggers scanned huge amounts of patient data in the electronic health record and flagged individuals at risk for delays in follow-up of cancer-related abnormal clinical findings.  Records of all patients flagged by the computerized trigger algorithm in the intervention group were reviewed to determine the presence of delay and if delay was confirmed, we communicated this information to their clinicians. We found that patients seeing clinicians who were notified of potential delays had more timely diagnostic evaluation for both prostate and colon cancer and more patients in the intervention part of the study had received diagnostic evaluation by the time we completed our final review.
Author Interviews, Colon Cancer, Nutrition / 23.08.2015

MedicalResearch.com Interview with: Dr Andrew Kunzmann & Dr Helen Coleman Joint first authorsCentre for Public Health Queen’s University Belfast Northern Ireland Medical Research: What is the background for this study? Response: There is now a large amount of evidence to suggest that individuals who consume diets high in fiber tend to be at a lower risk of bowel (colorectal) cancer. However, it is not known whether this association begins at the early stages of bowel cancer development or at later stages, in individuals with polyps (adenomas) that can lead to bowel cancer if left untreated. The best source of dietary fiber (cereals, fruit or vegetables) for bowel adenoma and cancer prevention is also debatable. We analysed data from individuals taking part in a large U.S trial assessing bowel screening, who completed a dietary questionnaire and received sigmoidoscopy screening at the start of the trial and received further screening 3 to 5 years later. This allowed us to investigate whether individuals with higher fiber diets had a lower risk of developing their first left-sided adenoma, but also for having adenomas recur at a later time, or indeed risk of bowel cancer, than individuals with diets low in fiber. By analysing only the screened participants, everyone had an equal opportunity to have their recurrent adenomas diagnosed – something that previous studies of dietary fiber have been unable to address.
Author Interviews, Biomarkers, Brain Cancer - Brain Tumors, Chemotherapy, Neurology, Radiation Therapy / 20.08.2015

Jorg Dietrich, MBA MMSc MD PhD Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical SchoolMedicalResearch.com Interview with: Jorg Dietrich, MBA MMSc MD PhD  Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an important issue in oncology. Specifically, management of acute and delayed neurotoxicity of chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet clinical need to better characterize the effects of standard cancer therapy on the normal brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and promote repair of treatment-induced damage. In this study, we demonstrate that standard chemotherapy and radiation in patients treated for glioblastoma is associated with progressive brain volume loss and damage to gray matter – the area of the brain that contains most neurons. A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to, during and following standard chemoradiation to characterize the pattern of structural changes that occur as a consequence of treatment.
Alcohol, Author Interviews, BMJ, Brigham & Women's - Harvard, Cancer Research / 19.08.2015

Dr. Yin Cao MPH, ScD Postdoctoral Fellow, Department of Nutrition Harvard T. H. Chan School of Public HealthMedicalResearch.com Interview with: Dr. Yin Cao MPH, ScD Postdoctoral Fellow, Department of Nutrition Harvard T. H. Chan School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Cao: Light-to-moderate drinking, defined as up to 1 drink (roughly corresponds to a 355ml bottle of beer, or a small [118-148 ml] glass of wine or 44ml of liquor) for women and up to 2 drinks for men, is prevalent in many western countries. It is believed that light-to-moderate drinking may be healthy for the heart. However, the influence of light-to-moderate drinking on risk of overall cancer is less clear, although it is well known that heavy alcohol intake increases risk of several cancers, including cancers of colorectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. Also because drinkers are more likely to be smokers, and smoking is the major risk factor for all of the alcohol-related cancers (mentioned above) except breast cancer, it is thus difficult to tease out the influence of alcohol on cancer in studies among a mixed population of ever and never smokers. In particular, it is important to know how light and moderate drinking would affect cancer risk particularly among never smokers, who now make up the majority of the population in many western countries. Our main findings are that, light-to-moderate drinking minimally increases risk of overall cancer. For men, the association with alcohol related cancers was primarily observed among smokers, and light to moderate drinking did not appreciably increase risk in never smokers. Among women, even consumption of up to one drink per day was associated with increased risk of alcohol-related cancers (mainly breast cancer) for both never and ever smokers.
Anesthesiology, Author Interviews, Breast Cancer, Journal Clinical Oncology, Surgical Research / 19.08.2015

Jaclyn Bradley Palmer, MM, MT-BC University Hospitals Of Cleveland Cleveland, OHMedicalResearch.com Interview with: Jaclyn Bradley Palmer, MM, MT-BC University Hospitals Of Cleveland Cleveland, OH  Medical Research: What is the background for this study? What are the main findings? Response: Patients awaiting breast cancer surgery may be understandably anxious. While pharmacologic intervention may reduce anxiety, higher doses of preoperative drugs can depress circulation and respiration, making alternative measures a particular interest. Music therapy is the clinical use of music interventions to accomplish individualized goals within a therapeutic relationship by a board-certified music therapist. While music in surgery has been researched under the label of "music therapy", many of the studied investigations illicit recorded music provided by non-music therapy staff, making it truly "music medicine" practices instead. In this investigation, the effect of both live and recorded music therapy on anxiety, anesthesia requirements, recovery time and patient satisfaction were studied perioperatively. Breast cancer surgery patients were engaged in a brief music therapy session which consisted of one live or recorded preferred song choice, followed by discussion and processing of emotions. Compared to usual care, both live and recorded music therapy groups experienced significantly greater reductions in anxiety (p<.001) with point reductions of 27.5 (42.5%) and 26.7 (41.2%), respectively. During surgery, both music groups listened to music-therapist selected recorded, instrumental harp music, chosen for it's evidence-based therapeutic value of smooth lines, consistent volumes and stable melodies. In measuring the amount of interoperative drug (propofol) needed to reach moderate sedation, the intraoperative music was not found to have an effect in this trial. Patient satisfaction was universally high in all three study groups. Those who received live music preoperatively were discharged an average of 12.5 minutes sooner than those who received recorded music preoperatively, although neither music group was dischanged significantly sooner than the control group. Subjective reactions to the music interventions relayed that music therapy in surgery was an enjoyable addition.
Author Interviews, Ovarian Cancer / 18.08.2015

Oleh Taratula,PhD Assistant Professor Oregon State University/Oregon Health & Science University College of PharmacyMedicalResearch.com Interview with: Oleh Taratula, PhD Assistant Professor Oregon State University/Oregon Health & Science University College of Pharmacy MedicalResearch: What is the background for this study? Dr. Taratula: The background for the study consists of previous work we had published in the lab using photodynamic therapy (PDT) as the stand alone treatment modality. We were successful in synthesizing and incorporating the photodynamic nanoplatform in the treatment for ovarian cancer, but our current graduate student, Canan Schumann said he could make the therapy more efficient using his current research on gene therapy. The gene therapy he is currently working on is the delivery of siRNA targeted to the multifaceted oncogenic protein DJ-1 which has been implicated in antioxidative stress defense as well as the overall survival of ovarian cancer. Cancer is highly intelligent able to adapt quickly to new insults that it comes across, even ROS formed inside the cell. Cancer cells can even upregulate a whole host of antioxidant stress response proteins to combat the formation of or scavenge already created ROS. The idea was can we combine our currently used PDT, which uses the generation of reactive oxygen species (ROS) as its cytotoxic mechanism of action, coupled with gene therapy targeted to DJ-1, in hope to drastically increase ROS inside the cell leading to a more pronounced cell death.
Author Interviews, Chemotherapy, Lancet / 17.08.2015

Bernardo L. Rapoport M. D. The Medical Oncology Centre of Rosebank Johannesburg, South AfricaMedicalResearch.com Interview with: Bernardo L. Rapoport M. D. The Medical Oncology Centre of Rosebank Johannesburg, South Africa Medical Research: What is the background for this study? What are the main findings? Dr. Rapoport: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared side effects of chemotherapy, and can lead to dose reductions or discontinuations of life-extending anti-cancer therapy. In the past, the serotonin (5-HT3) receptor antagonists, such as granisetron, palonosetron , and ondansetron, have shown effectiveness in preventing acute CINV (0-24 hours after chemotherapy administration), but many chemotherapies, such as cisplatin, carboplatin, and anthracycline/cyclophosphamide combinations, can cause delayed chemotherapy-induced nausea and vomiting that occurs from >24 hours to 5 days or more after chemotherapy. Neurokinin-1 receptor antagonists (NK-1 RAs) work though the substance P signaling pathway and are effective at preventing the delayed phase of chemotherapy-induced nausea and vomiting. Aprepitant was the first NK-1 RA to come to market in 2003, followed by a fixed dose of netupitant plus palonosetron late last year.
Author Interviews, Biomarkers, Pancreatic / 17.08.2015

Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary, University of London London UKMedicalResearch.com Interview with: Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary University of London London UK  Medical Research: What is the background for this study? What are the main findings? Dr. Crnogorac-Jurcevic: Pancreatic adenocarcinoma (PDAC) is one of the most difficult cancers to detect. More than 80% of patients usually present at a late stage, with either locally advanced or with already metastatic disease. This is one of the major reasons for a bleak prognosis of this malignancy, which is typically 3-6 months and with <5% five-year survival. However, if patients are diagnosed with stage II disease, the survival rate is 20%, and at stage I, in patients with very small tumours, the five-year survival can increase up to 60%. In order to find biomarkers for early detection of this disease, we have performed in depth GeLC/MS/MS (SDS-PAGE-liquid chromatography-tandem mass spectrometry) analysis of 18 proteomes of urine samples collected from healthy controls, chronic pancreatitis, and patients with Pancreatic adenocarcinoma and obtained around 1500 non-redundant proteins. From these, three proteins, LYVE-1, REG1A, and TFF1, were selected for further analysis based on their known biological functions and statistical difference in comparisons of the experimental groups. These biomarkers were subsequently validated using ELISA assays in a multicenter cohort of urine samples: 87 from healthy people, 92 from patients with chronic pancreatitis, and 192 from PDAC patients. Multiple logistic regression was then applied: when comparing Pancreatic adenocarcinoma with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the three biomarkers combined into a panel were 0.89 (95% confidence interval: 0.84–0.94) in the training dataset (70% of the data) and 0.92 (95% confidence interval: 0.86–0.98) in the validation dataset (30% of the data). When the results from the analysis of PDAC stage I–II (n=71) urine samples were compared with the healthy urine specimens, the panel achieved AUCs of 0.90 (95% confidence interval: 0.84–0.96) and 0.93 (95% confidence interval: 0.84–1.00) in the training and validation datasets, respectively. In comparison to matching plasma CA19.9 values, the only Pancreatic adenocarcinoma biomarker in widespread clinical use (albeit mostly for monitoring of the disease), the panel achieved a higher AUC of 0.97 (95% confidence interval: 0.94–0.99) than CA19.9 (AUC 1/4 0.88; 95% confidence interval: 0.81–0.95, P=0.005). When combined with CA19.9, increased AUC of 0.99 (95% confidence interval: 0.97–1.00, P=0.04) was achieved, but this was not seen in a panel combined with plasma CA19.9 in stage I–IIA PDAC (n =17) vs. healthy sample comparison.
Author Interviews, Lung Cancer, Outcomes & Safety, Surgical Research, University of Michigan / 15.08.2015

Tyler Grenda, MD House Officer VI Section of General Surgery Department of Surgery University of Michigan MedicalResearch.com Interview with: Tyler Grenda, MD House Officer VI Section of General Surgery Department of Surgery University of Michigan   Medical Research: What is the background for this study? What are the main findings? Dr. Grenda: The main purpose for this study was to better understand the factors underlying differences in mortality rates for hospitals performing lung cancer resection.  The methodology we used included only the highest and lowest mortality hospitals (Commission on Cancer accredited cancer programs) so the sampling frame was specific. There are wide variations in mortality rates across hospitals performing lung cancer resection (overall unadjusted mortality rates were 10.8% vs. 1.6%, respectively.
Author Interviews, Breast Cancer, NEJM, Radiation Therapy / 14.08.2015

MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes. Medical Research: What are the main findings? Dr. Poortmans: We found a decreased risk for development of distant metastases of 3% at 10 years, translated in a 3% overall improved overall disease free survival. Up to now, It leads to an improvement of 1.6% in overall survival at 10 years, which is, in contrast to the earlier 2 findings, just not statistically significant (borderline at p = 0.06). On the other hand, breast cancer related mortality is significantly improved and we did not see an increase in non breast cancer related causes of death. Overall toxicity was limited with only a significant increase in pulmonary toxicity, however to a low grade in the big majority of those patients. The benefit in overall survival is in a similar order of magnitude than adding for example taxanes to anthracycline-based adjuvant chemotherapy for a similar patient population as ours. Medical Research: What should clinicians and patients take away from your report? Dr. Poortmans:  First, we should appreciated that the regional (lymph node) recurrence rate is a poor endpoint for evaluation of also locoregional treatment. This can be explained by the fact that once distant metastases are found, no further search for local (breast) or regional (lymph nodes) recurrences is performed any more, as this is not relevant anymore for treatment or prognosis. However, the spread of distant metastases might occur from cancer involvement of the lymph nodes, explaining why we saw the effect of the lymph node irradiation basically only on the rate of development of distant metastases.  As a second message, we can appreciate that the 3% decreased distant metastases rate did not yet fully translate into a survival benefit, which can be explained by the need for even longer follow-up than 10 years. The explanation lies simply in the fact that even after development of distant metastases, patients can live for quite some more years with, however, only very little chance for definitive cure.  Thirdly, we demonstrated with the quality assurance programme linked to this trial that radiation treatment as used those days (the accrual phase was from 1996 until January 2004) radiation therapy techniques should be nowadays considered as suboptimal with a lack of full coverage of the target volumes and delivery of a too high dose to the organs at risk. With modern techniques, we expect that the results will even be quite better.  And finally, that the overall outcome of breast cancer improved a lot: at the start of the trial, we estimated overall survival at 10 years being 50%, which we revised in 2000 to 75% and we ended up with more than 80%. Thereby, it becomes more of a challenge to demonstrate benefits of further improving treatment as the same relative improvement will be translated into a lower absolute improvement. Nevertheless, by more effectively preventing the development of distant metastases by improved systemic therapy (or even better by earlier detection with a lower basal rate of distant metastases) the importance of optimizing locoregional control becomes even higher. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Poortmans: o First of all we have to improve our ability to define which patients will gain most from this treatment. o Secondly, we have to further investigate how to optimize the technical aspects of this loco regional treatment and … o Thirdly how to optimally integrate all treatment aspects including locoregional ones and systemic ones. o Based on all this, we can develop and then provide the patients with shared decision making tools. Citation: Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer Philip M. Poortmans, Ph.D., Sandra Collette, M.Sc., Carine Kirkove, Ph.D., Erik Van Limbergen, Ph.D., Volker Budach, Ph.D., Henk Struikmans, Ph.D., Laurence Collette, Ph.D., Alain Fourquet, Ph.D., Philippe Maingon, M.D., Mariacarla Valli, M.D., Karin De Winter, M.D., Simone Marnitz, M.D., Isabelle Barillot, Ph.D., Luciano Scandolaro, M.D., Ernest Vonk, M.D., Carla Rodenhuis, Ph.D., Hugo Marsiglia, Ph.D., Nicola Weidner, Ph.D., Geertjan van Tienhoven, Ph.D., Christoph Glanzmann, Ph.D., Abraham Kuten, M.D., Rodrigo Arriagada, M.D., Harry Bartelink, Ph.D., and Walter Van den Bogaert, Ph.D. for the EORTC Radiation Oncology and Breast Cancer Groups N Engl J Med 2015; 373:317-327 July 23, 2015 DOI: 10.1056/NEJMoa1415369 MedicalResearch.com is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Philip.Poortmans@radboudumc.nl MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands   Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.
Annals Internal Medicine, Author Interviews, Cancer Research / 14.08.2015

Thomas F. Imperiale, MD Indiana University Medical Center Regenstrief Institute Indianapolis, IN 46202 MedicalResearch.com Interview with: Thomas F. Imperiale, MD Indiana University Medical Center Regenstrief Institute Indianapolis, IN 46202   Medical Research: What is the background for this study? Dr. Imperiale: The background is that colorectal cancer (CRC) screening is effective and cost-effective, but it is underutilized (35% of eligible persons in the U.S. are not current with screening; 28% have never been screened) and inefficient (persons at low risk have colonoscopy; persons at high risk have stool blood testing or nothing). We know about several risk factors for colorectal cancer and advanced, precancerous polyps. We wanted to see how those factors perform together in stratifying (or separating) risk among the 85% of the U.S. population that is considered to be “average-risk”. Medical Research: What are the main findings? Dr. Imperiale: We found that age, sex, whether a first-degree relative has or had colorectal cancer, cigarette smoking, and waist circumference do a good job in separating risk into the 4 categories described in the paper.  When tested in the validation subgroup, the risk estimates reproduced themselves fairly well. 
Author Interviews, Breast Cancer, Genetic Research, JAMA, Ovarian Cancer / 13.08.2015

Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114MedicalResearch.com Interview with: Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific. Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families.  Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family.
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