Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer / 08.04.2016

MedicalResearch.com Interview with: Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital  MedicalResearch.com: What is the background for this study? Dr. Sacher: The aim of this prospective study was to determine the accuracy, turnaround time and robustness of ddPCR-based liquid biopsy for the detection of EGFR and KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC). The detection of these mutations is key to selecting optimal therapy for patients with this disease. Currently, the standard of care is to perform tissue biopsies on patients in order to obtain material to detect these mutations and make decisions about treatment. Frequently, patients undergo multiple tissue biopsies during the course of their treatment. We sought to determine if liquid biopsy could quickly and accurately detect these mutations with the ultimate goal of understanding how to use these tests to select treatment for patients. (more…)
Author Interviews, Breast Cancer, Endocrinology, Journal Clinical Oncology, Menopause / 08.04.2016

MedicalResearch.com Interview with: Karin Ribi, PhD, MPH Head of Quality of Life Office IBCSG International Breast Cancer Study Group Bern Switzerland  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ribi: This study investigated the quality of life (QoL) outcomes for women in the Suppression of Ovarian Function (SOFT) trial. SOFT investigated the value of adding ovarian suppression (OFS) to tamoxifen and to determine the role of the aromatase inhibitor exemestane+OFS as adjuvant (post-surgery) therapies for hormone-sensitive early breast cancer. SOFT was conducted by the International Breast Cancer Study Group (IBCSG) in over 3000 premenopausal women from more than 500 centers worldwide. The primary analysis of SOFT compared tamoxifen alone with tamoxifen+OFS in over 2000 women, and showed that adding OFS to tamoxifen did not provide a significant benefit in the overall population of premenopausal women. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of OFS improved disease outcomes.[1] With regard to the QoL main findings, patients on tamoxifen+OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen+OFS. Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy. Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period. (more…)
Author Interviews, Cancer, Cancer Research, End of Life Care / 06.04.2016

MedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medicine New York Presbyterian Hospital New York City, New York 10065  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Prigerson: Patients need to know their prognosis to be informed consumers of end-stage cancer care. We found that most patients have an overly optimistic view of their life-expectancy and that few patients base their life expectancy estimate on communications with their healthcare providers. It was striking that 0% of black patients said their prognostic estimate was based on a medical professional. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Brigham & Women's - Harvard, PNAS / 06.04.2016

MedicalResearch.com Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114

MedicalResearch.com: What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed.

MedicalResearch.com: What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years. (more…)
Author Interviews, Cancer Research / 05.04.2016

MedicalResearch.com Interview with: Katriina Heikkila, PhD Lecturer, London School of Hygiene and Tropical Medicine Honorary Researcher, the Finnish Institute of Occupational Health MedicalResearch.com: What is the background for this study? Dr. Heikkila:  Governments across the world have set regulations on working time, many recommending a maximum of 48- or 55-hour working week but many men and women today regularly work longer than recommended maximum hours. Working exceedingly hours is associated with many adverse health outcomes, such as an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer has so far been unclear. To address this gap in the knowledge, we investigated the association between weekly working hours and incident cancer using individual-level data from over 116 000 initially cancer-free men and women from 12 research studies from Finland, Denmark, Sweden, Germany, the Netherlands and the UK. (more…)
Author Interviews, Breast Cancer, JAMA, Nutrition, UCSD / 05.04.2016

MedicalResearch.com Interview with: Ruth E. Patterson, PhD Professor, Department of Family Medicine and Public Health Associate Director, Population Sciences Program Leader, Cancer Prevention Moores Cancer Center UC San Diego La Jolla, CA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Patterson: Our research team was intrigued with studies in mice showing that even when eating a high-fat diet, mice who were subjected to a 16-hour fasting regimen during the sleep phase were protected against abnormal glucose metabolism, inflammation and weight gain; all of which are associated with poor cancer outcomes. We had access to a study conducted in breast cancer survivors called the Women’s Healthy Eating and Living Study (WHEL).  Participants in this study completed food records, which give the time of eating meals and snacks.  We used the food records to estimate the average nightly fasting interval in 2413 breast cancer survivors.  Overall, we found that women who had a nightly fasting interval of less than 13 hours had a 36% increased risk of breast cancer recurrence and a nonsignificant increase in mortality.  We also found that women with a short nightly fast had poorer glucoregulation and worse sleep, both of which might explain the link to breast cancer. (more…)
Author Interviews, Cost of Health Care, JAMA, Prostate Cancer / 30.03.2016

MedicalResearch.com Interview with: HICOR portraits, Nov. 4, 2014 Joshua A. Roth, PhD, MHA Assistant Member AHRQ Patient-Centered Outcomes Research K12 Scholar Hutchinson Institute for Cancer Outcomes ResearchJoshua A. Roth, PhD, MHA Assistant Member AHRQ Patient-Centered Outcomes Research K12 Scholar Hutchinson Institute for Cancer Outcomes Research MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Roth: PSA prostate cancer screening is controversial because of uncertainty about the overall benefit-risk balance of screening and conflicting recommendations from a variety of prominent national panels. For example, there is debate about whether the cancer early-detection benefits of screening outweigh potential harms related to overdiagnosis of prostate cancer and associated overtreatment (for example, surgery and/or radiation therapy). However, this benefit-risk balance largely depends on how screening programs are structured (for example, the age range over which screening occurs, how often screened occurs, and the PSA level that triggers biopsies) and how screening detected prostate cancers are managed. With these factors in mind, we developed a simulation model to estimate the morbidity, mortality, and cost outcomes of many PSA screening approaches that have been proposed by national panels or discussed in the peer-reviewed literature. The model calculates these outcomes using inputs from national databases and major PSA screening clinical trials. The primary outcome of our model was the cost per quality-adjusted life year gained—a measure that reflects the value of medical interventions through impacts on cost, survival, and health-related quality of life. We don’t have explicit rules for willingness to pay per quality-adjusted life year in the United States, but interventions that cost $100,000 to $150,000 per quality-adjusted life year are generally considered to be of at least low to moderate value (whereas, for example, an intervention that costs $400,000 per quality-adjusted life year would be generally considered to be of very poor value). Using the model, we found that more conservative PSA screening strategies (that is, those with less frequent screening and higher PSA level thresholds for biopsy referral) tended to be more cost-effective than less conservative strategies. Importantly, we found that no strategy was likely to be of high value under contemporary treatment patterns where many men with low-risk prostate cancer (that is, those with a Gleason score lower than 7 and clinical T2a stage cancer or lower) receive treatment with surgery or radiation therapy, but several strategies were likely to be of at least moderate value (cost per qualityadjusted life-year=$70 831-$136 332) with increased use of conservative management (that is, treating only after clinical progression) for low-risk, screen-detected cancers. (more…)
Author Interviews, Cancer Research, Technology, UCLA / 26.03.2016

MedicalResearch.com Interview with: Dr. David Wong D.M.D, D.M.S.C Professor Associate Dean for Research Director for UCLA Center for Oral/Head & Neck Oncology Research (COOR) Felix and Mildred Yip Endowed Chair in Dentistry UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wong: The EFIRM technology is an electrochemical technology developed for the optimal detection of saliva targets for molecular diagnostics. It is a multiplexible platform (nucleic acid and proteins) that has sensitivity and specificity that comparable with PCR and luminex-based assays. It permits direct target detection in bio-samples without processing. (more…)
Author Interviews, Cancer Research, JAMA, Pediatrics / 25.03.2016

MedicalResearch.com Interview with: Lee J. Helman, MD Senior Investigator Pediatric Oncology Branch Head, Molecular Oncology Section Acting Director, Center for Cancer Research and CCR Scientific Director for Clinical Research National Cancer Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Helman: It was known that most gastrointestinal stromal tumors (GISTS) that occur in children and young adults do not contain cKIT or PDGFRA mutations that drive more than 90% of adult GIST tumors.  Since GISTs are quite rare in the pediatric and young adult population, we decided to establish a clinic at NIH that would allow us to study the most patients to try to define these tumors both clinically and molecularly. We were able to bring both patients and physicians interested in pediatric GIST from around the country to the NIH to begin to collect and study these patients. Of the 95 patients in this cohort study that lacked cKIT or PDGFRAmutations, 84 were found to have succinate dehydrogenase (SDH) deficient (SDH-deficient) GIST (75% due to SDH A, B, C, or D mutations, and 25% due to SDHC promoter hypermethylation. Since these tumors are driven by SDH loss and not due to KIT or PDGFR mutations, they do not generally respond to standard treatments for GIST that target these kinases. The mechanism of SDH-deficiency is important, since SDH mutations are commonly germ line and therefore require genetic counseling and family testing, while the SDHC promoter methylation is not a germ line alteration and therefore does not require genetic counseling.  Finally, any patient with SDH-deficient GIST is also at risk for development of paraganglioma and should be screened on a regular basis for these tumors.  (more…)
Annals Internal Medicine, Author Interviews, Breast Cancer / 21.03.2016

MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Elmore: Our team began studying diagnostic agreement among pathologists while interpreting breast biopsies in 2009. Early findings from the Breast Pathology Study (B-Path) were published in March 2015 in the Journal of the American Medical Association and indicated strong agreement among pathologists when diagnosing invasive breast cancer or benign breast tissue. Agreement, however, was much lower for ductal carcinoma in situ (DCIS) and atypia. Results from this study raised concerns that a high percentage of breast biopsies may be inaccurately diagnosed. These concerns were amplified in the media with statements like “as many as one-in-four biopsies are incorrectly diagnosed.” Statements like this inaccurately depicted the results of our study, which included a test set weighted heavily with DCIS and atypia cases. It is important to consider the percentage that each outcome category contributes to the overall number of biopsies in the U.S. population as we found that the agreement rate of pathologists varies drastically across these diagnostic categories. Atypia in Breast Tissue Elmore Image In the new work published in Annals of Internal Medicine, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates, In an effort to help physicians and patients better understand what the B-Path results mean for women, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates. When adjusted using population-based predictive value estimates, the B-Path results indicate that pathologists’ overall interpretations of breast biopsies would be confirmed by an expert panel 92 out of 100 biopsies, with more of the initial diagnoses over-interpreted rather than under-interpreted. Of concern, our results noted that among 100 breast biopsies given an initial diagnosis of atypia, less than half of these cases would be given a diagnosis of atypia after review by a panel of three experienced breast pathologists. Over half of the biopsies would be downgraded from atypia to a diagnosis of benign without atypia after review. (more…)
Author Interviews, Cancer Research, Imperial College / 21.03.2016

MedicalResearch.com Interview with: Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pardo: Metastatic dissemination, the ability of tumour cells to go and colonise organs distant from the primary disease site, is the principal cause for failing to cure patients with cancer. This is particularly true in the case of breast cancer where resection of local disease offers good chances of cure but metastatic dissemination that may appear at a later stage carries very poor prognosis. Surgical resection is also the only true curative strategy for localised lung cancer. Hence, a better understanding of the mechanisms controlling the dissemination of tumour cells is likely to propose novel targets for combination therapy that will improve the survival of cancer patients. Here, we showed that an enzyme, named MARK4, controls the ability of lung and breast cancer cells to move and invade. When we lower MARK4 levels, it prevents cancer cells from moving by changing their internal architecture, making them unfit to invade. Consequently, these cells were unable to efficiently form metastasis in mouse cancer models. Confirming the role of this enzyme in cancer, we show that breast and lung cancer patients with increased levels of MARK4 in their tumours have poorer prognosis. We found that what controls the levels of MARK4 in cells is miR-515-5p, a small oligonucleotide sequence called a microRNA. When present in the cells, miR-515-5p prevents the expression of MARK4. Incidentally, the loss of miR-515-5p correlates with increased metastasis and poorer prognosis in mouse cancer models and patients, respectively. (more…)
Author Interviews, Biomarkers, Breast Cancer / 20.03.2016

MedicalResearch.com Interview with: Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer. Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them. (more…)
Author Interviews, Cancer Research / 19.03.2016

MedicalResearch.com Interview with: Douglas.A. Lauffenburger PhD Ford Professor of Biological Engineering, Chemical Engineering, and Biology Head, Department of Biological Engineering Massachusetts Institute of Technology Cambridge, MA 02139  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lauffenburger: We aimed to advance understanding concerning causes of tumor resistance to kinase inhibitor drugs, which limits effectiveness for many therapeutics even when indicated by specific genetic mutations in the new ‘personalized medicine’ paradigm.  We discovered a new mechanism underlying this resistance at least for a number of otherwise promising drugs currently in clinical use as well as further clinical trials.  Our discovery was based on realizing that the same oncogenic signaling driving tumor cell proliferation and invasiveness at the same time activates proteolytic shedding of receptor tyrosine kinases not involved in the targeted oncogenic pathway, shutting down additional signaling inputs.  Thus, when the targeted pathway is inhibited by the intended drug, this shedding is concomitantly diminished — now permitting “bypass" pathways to be activated downstream of these alternative receptor inputs.  Moreover, we showed that measurement of a set of key shed receptors (primarily AXL and MET, in our examined case of MEK pathway inhibitors for melanoma and triple-negative breast tumors) in patient blood serum samples could predict effectiveness of these inhibitors: when the shed levels were high, the drugs were less effective because of the correspondingly great potential for bypass signaling upon drug treatment.  In follow-up mouse experiments, we demonstrated increased effectiveness of a MEK inhibitor when combined with either an AXL inhibitor or a proteolysis inhibitor, thereby confirming the mechanism and proving an avenue for overcoming it. (more…)
Author Interviews, Breast Cancer, Lancet / 18.03.2016

MedicalResearch.com Interview with: Professor Jack Cuzick, PhD, FMedSci, FRCP(hon) Director, Wolfson Institute of Preventive Medicine and Head, Centre for Cancer Prevention Queen Mary University of London. MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cuzick: Ductal carcinoma in situ (DCIS) is a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year. Our IBIS-II DCIS trial looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery. The two groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant. The similar NSABP B-35  trial found a 29% reduction with anastrozole and the combined analysis of the two trials indicated a significant 21% reduction. The key difference between the two groups were in the side effects of the medication. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However more fractures and musculoskeletal side effects were seen among those receiving anastrozole. (more…)
Alcohol, Author Interviews, Breast Cancer, Genetic Research, PLoS / 18.03.2016

MedicalResearch.com Interview with: Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) Houston, TX 77204-5056  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers. (more…)
Author Interviews, Breast Cancer / 14.03.2016

MedicalResearch.com Interview with: Professor Nigel Bundred MD, FRCS Professor of Surgical Oncology Institute of Cancer Sciences University Hospital of South Manchester MedicalResearch.com: What is the background for this study? Dr. Bundred: HER-2 is a cancer-causing gene which is expressed in some cells by having more copies of the gene and predicts for early relapse and metastasis from the tumour. Despite this, even in the absence of anything other than local treatment, some 50% of patients still survive for five years without relapse. Herceptin was discovered and licensed for use in 2006 because it improved survival when given with chemotherapy after surgery, from 66% at five years to 90% at five years. The use of Herceptin and chemotherapy before surgery to shrink the tumour indicates that around 30% of patients have a complete pathological response with this treatment. Combination of dual anti-HER-2 therapies and  Neoadjuvant chemotherapy given for six months before surgery has been shown to increase pCR rate to 50% and a single study utilising the combination of pertuzumab and trastuzumab (two anti-HER-2 monoclonal antibodies) given for four months revealed a 16.8% pCR rate. (more…)
Author Interviews, Cancer, Cancer Research, Cost of Health Care / 14.03.2016

MedicalResearch.com Interview with: Hrishikesh Kale School of Pharmacy Virginia Commonwealth University MedicalResearch.com: What is the background for this study? What are the main findings? Response: The cost of cancer care in the United States is extremely high and escalating every year. Because of increased cost sharing, patients are paying higher out-of-pocket costs for their treatments. Along with high medical expenses, cancer survivors face problems such as loss of employment and reduced productivity. It has been well-established in the literature that because of high out-of-pocket costs, many cancer survivors forgo or delay medical care and mental health-related services and avoid filling prescriptions. This puts their physical and mental health at risk. A related issue is the growing number of cancer survivors in the U.S. As of January 2014, there were approximately 14.5 million cancer survivors in the U.S. By 2024, this number is expected to reach 19 million as a result of improved survival among patients with cancer along with an aging population. Therefore, we decided to investigate the prevalence and sources of financial problems reported by a nationally representative sample of cancer survivors from the 2011 Medical Expenditure Panel Survey. We also studied the impact of cancer-related financial burden on survivors’ health-related quality of life and psychological health. (more…)
Author Interviews, Prostate Cancer, Surgical Research / 11.03.2016

MedicalResearch.com Interview with: Naveen Pokala, MD Division of Urology University of Missouri Columbia, MO 65212 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pokala: The main purpose of the study was to determine survival outcome following salvage prostatectomy in men that fail radiation therapy. Radiation and surgery are the main modalities utilized to treat localized prostate cancer. When patients fail radiation treatment, traditionally, only hormonal treatment was offered. With refinements in surgical techniques, a select few of these patients that have recurrence after radiation may benefit with salvage surgery. Salvage prostatectomy is a complex procedure because prior radiation makes this procedure tenuous, but this procedure is offered in most major tertiary medical centers. (more…)
Author Interviews, Cancer Research, JAMA / 11.03.2016

MedicalResearch.com Interview with: Joseph Unger, PhD, MS SWOG Statistical Center Assistant Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center Affiliate Assistant Professor, Health Services Research, University of Washington Seattle, WA  98109-1024 MedicalResearch.com: What is the background for this study? Dr. Unger: The rate at which trials are positive has previously been examined, and the relationship between trial results and publication rates in the context of publication bias has also been studied. But the comparative scientific impact of positive vs negative clinical trials using citation data has not been investigated We used the phase III trial database of SWOG, a major national cooperative clinical trials group, in combination with its trial publication database and citation data from Google Scholar, to compare the scientific impact of positive vs negative phase III cancer clinical treatment trials. (more…)
Author Interviews, Breast Cancer, Diabetes / 09.03.2016

MedicalResearch.com Interview with: Dr. Zorana Andersen Department of Public Health Center for Epidemiology and Screening University of Copenhagen  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Andersen: Diabetes is associated with increased risk of breast cancer, but exact mechanisms are unknown. The role of insulin has been debated. High mammographic density (MD) is one of the strongest predictors and a biomarker of breast cancer risk. Few studies have linked diabetes to mammographic density, finding none or weak inverse associations, but none had data on diabetes treatment. We examined whether diabetes and diabetes treatment are associated with mammographic density in a prospective cohort study of Danish women above age of 50 years. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Andersen: Women with diabetes, as well as clinicians working with diabetes and breast cancer and breast cancer screening, would have interest to know how different diabetes treatment can affect breast density, and hereby possibly breast cancer risk. For example, diabetic women taking insulin may possibly benefit from informing radiologists at breast cancer screening about their insulin use, due to increased breast density and increased risk of masking bias. (more…)
Author Interviews, BMJ, Cancer Research, Colon Cancer, Psychological Science / 09.03.2016

MedicalResearch.com Interview with: Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) MedicalResearch.com: What is the background for this study? Response: Randomised controlled trials have demonstrated that screening for colorectal cancer (CRC) can reduce CRC related mortality, but the total benefit and harm of national cancer screening programmes are under debate. Saving relatively few lives requires a large number of people to be screened. Most people who attend screening will never develop cancer, but may be exposed to potential psychological stress by participation. Cancer is one of the largest threats to peoples’ health, and participating in screening for cancer might therefore cause anxiety. In Norway, colorectal cancer incidence has nearly tripled since the 1950s, and currently a large randomised pilot study of a national screening programme (Bowel Cancer Screening in Norway) is investigating the effect of screening on reduction in CRC incidence and mortality. As part of an evaluation of the benefits and harms of the pilot, we investigated the psychological effect of screening participation in a large group of participants. Of particular interest to us were participants who received a positive screening result and were referred to colonoscopy. (more…)
Author Interviews, Biomarkers, Breast Cancer / 09.03.2016

MedicalResearch.com Interview with: Michele Orditura MD, PhD Associate Professor in Medical Oncology Faculty of Medicine, Second University of Naples Naples Italy  MedicalResearch.com: What is the background for this study? Prof. Orditura: In the last few years increasing evidence suggests that cancer-related inflammatory response plays a crucial role in the development and progression of several malignancies. Neutrophil to lymphocyte ratio (NLR), calculated as the neutrophil count divided by the lymphocyte count , may represent an easily measurable and inexpensive marker of systemic inflammation. Several studies have reported NLR as an unfavourable prognostic indicator for patients with gastrointestinal, lung, renal and gynaecological cancers. In the breast cancer setting, the results of published trials evaluating the relationship between NLR and outcome are controversial, and a recent meta-analysis including eight trials published between 2012 and 2014 has shown that elevated NLR is strongly associated with poor survival. In addition, the available data mainly concern women of Asian race and only three papers have included patients of Europe race. The main aim of this study was to clarify the correlation between pre surgery NLR and distant metastasis-free survival in a series of 300 Italian patients with early breast cancer. The propensity score-matched analysis was chosen for statistical evaluation to avoid risk of confounding bias. (more…)
Author Interviews, BMJ, Prostate, Prostate Cancer, Urology / 08.03.2016

MedicalResearch.com Interview with: Robert Nam, MD, FRCSC Ajmera Family Chair in Urologic Oncology Professor of Surgery University of Toronto Head, Genitourinary Cancer Site Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto, Ontario MedicalResearch.com: What is the background for this study? Response: Prostate cancer treatment is associated with a number of complications including erectile dysfunction and urinary incontinence. Two years ago, we published a paper examining other, previously undescribed complications. The most controversial finding was a significantly increased risk of secondary cancers among men treated with radiotherapy. We therefore wanted to assess this in a meta-analysis, examining all the research currently available on the topic. MedicalResearch.com: What are the main findings? Response: We found that, for patients with prostate cancer, radiotherapy treatment was associated with significantly increased rates of bladder cancer, colorectal cancer and rectal cancer. There wasn't an increased risk for other cancers such as lung and blood system cancer. However, the absolute rates of these cancers remained low (1-4% of patients). (more…)
Author Interviews, Brigham & Women's - Harvard, Melanoma, Ophthalmology / 08.03.2016

MedicalResearch.com Interview with: Ines Laines MD and Deeba Husain MD Associate Professor Ophthalmology Harvard Medical School Investigator Angiogenesis Laboratory Retina Service Massachusetts Eye and Ear Infirmary Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Uveal melanoma (UM) is the most common malignant tumor of the eye in adults. More than half of the patients are long-term survivors. It is well established for other malignancies that cancer survivors are especially prone to developing independent second primary neoplasms (SPNs) and that their characteristics vary according to the site of the first primary tumor. Multifactorial causes seem to be involved, including environmental exposures and genetic risk factors. The relevance of the treatment modalities applied to the first tumor also seem to play a role, in particular radiation therapy, which is currently the gold-standard treatment for most uveal melanoma. This risk is most pronounced in the organs within the irradiated fields, but has also been described in sites not directly exposed to radiation. Despite growing knowledge about treatment-induced effects on the occurrence of SPNs in patients with other malignancies, data is insufficient for uveal melanoma. We present a population-based analysis of the Surveillance, Epidemiology, and End Results (SEER) database, which is a well-validated public database with a case ascertainment rate of 98%. In this study, we evaluated whether patients with UM demonstrate an increased incidence of  second primary neoplasms compared to the general population, including an analysis on whether radiation therapy is associated with a higher risk of thesesecond primary neoplasms. (more…)
Author Interviews, Chemotherapy, Lancet / 08.03.2016

MedicalResearch.com Interview with: Dr Christina H Ruhlmann PhD Department of Oncology Odense University Hospital, Denmark  MedicalResearch.com: What is the background for this study? Response: The background for the GAND-emesis study is the result of a phase II study in patients with gynecological cancer receiving fractionated radiotherapy and concomitant weekly cisplatin 40 mg/m2. In that study, patients received weekly antiemetic prophylaxis with palonosetron and prednisolone, and we found that 57% of patients were continuously free from emesis (sustained no emesis) during 5 weeks of treatment. We hypothesized that the addition of a NK1 receptor antagonist could increase the number of patients with sustained no emesis, and we therefore planned the GAND-emesis study: a multinational, randomised, placebo-controlled, double-blind study that has recently been published. MedicalResearch.com: What are the main findings? Response: In the GAND-emesis study we compared efficacy of weekly antiemetic prophylaxis with fosaprepitant, palonosetron, and dexamethasone to placebo, palonosetron, and dexamethasone during 5 weeks of radiotherapy and concomitant weekly cisplatin 40 mg/m2 for cervical cancer. The primary endpoint was sustained no emesis during 5 weeks of treatment (competing risk analysis). We found that the proportion of patients with sustained no emesis was 48.7% for the placebo group compared with 65.7% for the fosaprepitant group, and the treatments were well tolerated. To our knowledge, this is the first study to investigate the efficacy of a NK1 receptor antagonist during 5 weeks of chemoradiotherapy. (more…)
Author Interviews, Breast Cancer, FASEB / 07.03.2016

MedicalResearch.com Interview with: Michelle L. Halls BBiomedSci(Hons), PhD NHMRC Career Development Fellow Drug Discovery Biology Theme Monash Institute of Pharmaceutical Sciences Monash University Parkville Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Halls: Stress causes an increase in the release of hormones including adrenaline. Previous studies have found a link between stress and metastases in triple negative breast cancer. However, what occurs inside a cancer cell in response to adrenaline to drive cancer progression was not known. We have found that adrenaline can directly act on triple negative breast cancer tumour cells via a cell surface receptor called the beta2-adrenoceptor. We identified changes in signalling within the cell that make the tumour cell highly invasive by mapping the signalling pathways that were activated in these cells in response to stress. We found that different signalling pathways converge to amplify the final signal. This ‘positive signalling loop’ was linked to the increased invasion of these cells in response to stress, and was not identified in less aggressive breast cancer cells. This may allow future research to identify new ways to intervene and slow cancer progression. New therapies are important for triple negative breast cancer, as it is particularly aggressive and currently has limited treatment options. (more…)
Author Interviews, Biomarkers, Cleveland Clinic, Genetic Research, Personalized Medicine, Prostate, Prostate Cancer, Urology / 07.03.2016

MedicalResearch.com Interview with: Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Klein: Prostate cancer is an enigma. While this tumor is the second leading cause of cancer death among American men, most newly diagnosed disease detected by PSA screening is biologically indolent and does not require immediate therapy. Currently, the main clinical challenge in these men is to distinguish between those who can be managed by active surveillance from those who require curative intervention. Current clinical and pathological tools used for risk stratification are limited in accuracy for distinguishing between these scenarios. An abundance of research in the last decade has provided evidence that genomics can offer meaningful and clinically actionable biological information to help inform decision making, and current National Comprehensive Cancer Network (NCCN) guidelines on prostate cancer endorse the use of commercially available genomic tools for men considering active surveillance.[1] It has been previously shown that the 22-gene genomic classifier, Decipher, accurately predicts the likelihood of metastasis and prostate cancer specific mortality when measured on tissue from radical prostatectomy specimens.[2] In multiple validation studies, it performed with higher accuracy and discrimination compared to clinical risk factors alone. The current study[3] is the first to examine whether the use of Decipher might aid decision making when measured on biopsy tissue at the time of diagnosis. Men with available needle biopsy samples were identified from a study cohort that previously had Decipher performed on their matched radical prostatectomy tissue. In this cohort of mixed low, intermediate and high risk men, Biopsy Decipher predicted the risk of metastasis 10 years post RP with high accuracy, outperforming NCCN clinical risk categorization, biopsy Gleason score and pre-operative PSA. Furthermore, this study showed that Decipher reclassified 46% of patients into lower or higher risk classification compared to NCCN classification alone. The study also showed that Biopsy Decipher can identify men that are at high risk for adverse pathology as defined by the presence of primary Gleason pattern 4 or greater. (more…)
Author Interviews, Chemotherapy, Pancreatic, Vanderbilt / 07.03.2016

MedicalResearch.com Interview with: Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN MedicalResearch.com: What is the background for this study? Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease. The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival. MedicalResearch.com: What are the main findings? Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival. (more…)