Author Interviews, Cancer Research, Hepatitis - Liver Disease, HPV, JNCI, MD Anderson / 15.04.2016

MedicalResearch.com Interview with: Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers. (more…)
Author Interviews, Cancer Research, Inflammation, Microbiome, PLoS, UCLA / 15.04.2016

MedicalResearch.com Interview with: Robert H. Schiestl PhD Department of Environmental Health Sciences, Fielding School of Public Health, Department of Pathology Department of Radiation Oncology Geffen School of Medicine University of California Los Angeles, Los Angeles, California Medical Research: What is the background for this study? What are the main findings? Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation. (more…)
Author Interviews, Breast Cancer, Fertility, Gender Differences, Karolinski Institute, Mammograms, Radiology / 14.04.2016

MedicalResearch.com Interview with: Frida Lundberg | PhD Student Dept. of Medical Epidemiology and Biostatistics Karolinska Institutet Medical Research: What is the background for this study? Response: Fertility treatments involve stimulation with potent hormonal drugs that increase the amount of the sex hormones estrogen and progesterone. These hormones have been linked to breast cancer risk. Further, as these treatments are relatively new, most women who have gone through them are still below the age at which breast cancer is usually diagnosed. Therefore we wanted to investigate if infertility and fertility treatments influences mammographic breast density, a strong marker for breast cancer risk that is also hormone-responsive. Medical Research: What are the main findings? Response: We found that women with a history of infertility had higher absolute dense volume than other women. Among the infertile women, those who had gone through controlled ovarian stimulation (COS) had the highest absolute dense volume. The results from our study indicate that infertile women, especially those who undergo COS, might represent a group with an increased risk of breast cancer. However, the observed difference in dense volume was relatively small and has only been linked to a modest increase in breast cancer risk in previous studies.  As the infertility type could influence what treatment the couples undergo, the association might also be due to the underlying infertility rather than the treatment per se. (more…)
Author Interviews, JAMA, Thyroid / 14.04.2016

MedicalResearch.com Interview with: Dr. Luc G. T. Morris, MD, MSc Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York Medical Research: What is the background for this study? What are the main findings? Dr. Morris:  Over the past 30 years, the incidence of thyroid cancer in the US has tripled. It used to be a mystery why this was happening. But recently, many researchers have shown that this is mainly happening because of improvements in medical technology that allow us to better identify and biopsy small nodules in the thyroid gland. Many of these small nodules turn out to be thyroid cancers. In fact, up to 30% of healthy persons have small cancers in their thyroid glands, and nearly all of these would not go on to cause any problems for the person if the cancer were never discovered. In other words, a large reservoir of small thyroid cancers has always been present, like a huge submerged iceberg, but we are just getting better at finding them. Therefore, the dramatically rising incidence of thyroid cancer is best characterized as an "epidemic of diagnosis," not an epidemic of disease. This is highly relevant to patients found to have these small thyroid cancers, because it means that many of these cancers would not have caused problems for the patient, and that there would be no benefit (only potential harm) to diagnosing and surgically removing them. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Menopause / 14.04.2016

MedicalResearch.com Interview with: Giorgia Razzini, PhD Unit of Medical Oncology Civil Hospital Carpi Italy; MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Razzini: Hot flashes experienced by breast cancer patients is a significant clinical problem because there are few reliable treatment that are free of side effects and it sometime reduces compliance with endocrine therapy for prevention of cancer recurrence. Menopausal symtoms overall  heavily impact on quality of life.. Acclimat found that acupuncture combined with self-care for 3 months, is associated with significantly lower hot flash scores, compared to self-care alone ( advices on diet, physical exercise and psycoloigical support if needed). Beneficial effects persisted up to 6 months follow-up. These effects were not associated with significant adverse events. MedicalResearch.com: What should clinicians and patients take away from your report?  Dr. Razzini:  Research suggests that breast cancer women do not receive adequate care for menopausal symptoms in the clinical practice of most oncology department. Our study showed that oncologists can offer them specific integrative management strategy for menopausal symptoms including acupuncture and enhanced self-care to women with breast cancer, particularly in younger women when treatment with hormonal treatment is recommended, in order to help women to stay on their therapy and improve their quality of life. (more…)
Author Interviews, Chemotherapy, Lancet, Leukemia / 13.04.2016

MedicalResearch.com Interview with: Prof Jeffrey H Lipton, PhD, MD, FRCPC Princess Margaret Cancer Centre Toronto, ON Canada MedicalResearch.com: What is the background and purpose for this study? Dr. Lipton: Ponatinib is a third generation tyrosine kinase inhibitor that has been shown to be extremely effective in treating patients with chronic myeloid leukemia resistant to other drugs.  Because of this, it was decided to look at it in newly diagnosed patients in a randomized study against imatinib.  The study was terminated prematurely because of evidence of vascular toxicity that became evident in the phase 1 and 2 studies of ponatinib in previously treated patients with resistant disease.   (more…)
Aging, Author Interviews, Melanoma, Nature, Wistar / 08.04.2016

MedicalResearch.com Interview with: Ashani T. Weeraratna, Ph.D. Associate Professor Melanoma Research Center The Wistar Institute Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Weeraratna: The background for this study is the fact that advancing age remains the greatest risk factor for the development of many cancers, and melanoma is no exception. We found that age-related changes in normal skin, specifically dermal fibroblasts, increase both the metastatic potential and therapeutic resistance of melanoma cells. The most fascinating thing is that even targeted therapy, which should depend solely on the interaction between the drug and the target within the tumor cell is affected by the age of the microenvironment. (more…)
Author Interviews, BMJ, Cancer Research, Education / 08.04.2016

MedicalResearch.com Interview with: Dr Alex Ghanouni Research Associate UCL Research Department of Epidemiology and Public Health Health Behaviour Research Centre London MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ghanouni: This study comes out of growing concern among academics, doctors, and policymakers about the unintended harms of healthcare interventions. One prominent issue in the ongoing debate is ‘overdiagnosis’, that is detection of disease that would not have caused symptoms or death if it had remained undetected. There are many contexts in which overdiagnosis can occur but one of the most prominent is cancer screening, in which asymptomatic individuals undergoing testing may have slow-growing cancers detected that would never have otherwise come to light. However, because it is impossible to be sure which cancers are slow-growing and which are aggressive, most are treated. This means that overdiagnosis can lead to harm through the anxiety caused by a disease label and the negative effects of treatment (e.g. surgery) that is actually unnecessary. Despite professional concern about overdiagnosis, previous research has found that the public is mostly unaware that it exists. One study that was particularly relevant to our research was an Australian survey in which members of the public were asked whether they had encountered the term before and what they thought it meant. Although around half the sample stated that they had heard or seen the term before, only 41% were able to provide a definition that was approximately correct. We tested the extent to which this was true as part of an online survey of adults aged 50-70 years in the UK. We found that recognition of the term was very low (only 30%) and almost no-one (3%) gave an answer that was strictly accurate. Responses often indicated misconceptions (e.g. “misdiagnosis”, “false positive diagnosis”, or being “overly health conscious”). (more…)
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: DrDavid 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 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…)