Author Interviews, Cancer Research / 19.03.2016 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 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 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. 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 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 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 Interview with: Professor Nigel Bundred MD, FRCS Professor of Surgical Oncology Institute of Cancer Sciences University Hospital of South Manchester 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 Interview with: Hrishikesh Kale School of Pharmacy Virginia Commonwealth University 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 Interview with: Naveen Pokala, MD Division of Urology University of Missouri Columbia, MO 65212 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 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 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 Interview with: Dr. Zorana Andersen Department of Public Health Center for Epidemiology and Screening University of Copenhagen 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. 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 Interview with: Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret) 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 Interview with: Michele Orditura MD, PhD Associate Professor in Medical Oncology Faculty of Medicine, Second University of Naples Naples Italy 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 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 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. 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 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 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 Interview with: Dr Christina H Ruhlmann PhD Department of Oncology Odense University Hospital, Denmark 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. 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 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 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 Interview with: Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic 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 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 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. 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…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research / 06.03.2016 Interview with: Rong Li, Ph.D., Professor Holder of the Tom C. & H. Frost Endowment Department of Molecular Medicine Institute of Biotechnology Co-Leader, Cancer Development and Progression Program Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio What is the background for this study? What are the main findings? Dr. Li: The breast cancer susceptibility gene BRCA1 is well known for its function in double strand break DNA repair. However, the ubiquitous role of BRCA1 in DNA repair may not be sufficient to explain its tissue-specific tumor suppressor function in vivo. Using the “awesome power” of mouse genetics, we identified a previously unappreciated crosstalk between BRCA1 and a transcription regulator in mammary gland development. Importantly, we provide compelling evidence that this BRCA1 function is independent of its well-established DNA repair activity. What should clinicians and patients take away from your report? Dr. Li: The newly identified DNA repair-independent function of BRCA1 may provide new tools and targets for early prevention of BRCA1-associated breast cancer. (more…)
AACR, Author Interviews, Cancer Research, Lung Cancer, MD Anderson, Nutrition, Sugar / 05.03.2016 Interview with: Xifeng Wu, M.D., Ph.D Professor of Epidemiology and Dr. Stephanie Claire Melkonian  PhD Epidemiologist, Postdoctoral Research Fellow The University of Texas MD Anderson Cancer Center What is the background for this study? What are the main findings? Response: Glycemic index (GI) assigns foods an indexed value to show how quickly and how much carbohydrates in the food cause blood glucose levels to rise after eating and is a measure of overall carbohydrate quality. Glycemic load (GL) is a related measure that is calculated by multiplying Glycemic index by the amount of carbohydrates in grams in that specific food and by the amount consume, then dividing by 100. Previous studies have investigated the association of GI and GL with certain types of cancer, including colorectal, stomach, and pancreatic cancer, but there has been limited research into the association with lung cancer. We conducted a study using patients and control subjects from an ongoing case-control study of lung cancer conducted at MD Anderson. The patients were newly diagnosed and had not received treatment other than surgery. The healthy control subjects were selected from patient lists at Kelsey-Seybold Clinics, a large physician group in the Houston area. The study results encompass 1,905 cases and 2,413 controls. Using data collected from in-person interviews regarding health histories and dietary behaviors, we were able to categorize the study subjects according to their dietary Glycemic index and GL. What we found was that individuals in the highest category of GI were at an almost 50% increased risk for developing lung cancer as compared to those in the lowest group. This association was different based on different subtypes of cancer. Most interestingly, however, among those individuals that never smoked, high Glycemic index was associated with an almost 2 fold increased risk of lung cancer. In other words, we found a more profound association between GI and lung cancer in never smokers in this study. (more…)
Author Interviews, Cancer Research, Lancet, Leukemia, OBGYNE, Pediatrics / 04.03.2016 Interview with: Erin Marcotte, Ph.D. Assistant Professor Division of Epidemiology and Clinical Research Department of Pediatrics University of Minnesota What is the background for this study? What are the main findings? Dr. Marcotte: Recently there have been several studies that indicate a higher risk of immune-related disorders, such as type-I diabetes, asthma, and allergies, among children born by cesarean delivery. Our analysis used pooled data from 13 independent studies of childhood leukemia that were conducted in 9 different countries. We used data on over 33,000 children to investigate the relationship between birth by cesarean delivery and risk of childhood leukemia. We did not find an association between cesarean delivery overall and childhood leukemia. However, when we looked at emergency cesarean deliveries and pre-labor (planned) cesarean deliveries separately, we found a 23% increase in risk of acute lymphoblastic leukemia among children born by pre-labor cesarean delivery. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2016 Interview with: Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611 What is the background for this study? What are the main findings? Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.  (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology / 03.03.2016 Interview with: Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany What is the background for this study? Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients. For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk. What are the main findings? Dr. Gluz: The study has two major findings: We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67). Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up. (more…)
Author Interviews, Breast Cancer, Cancer Research, JNCI, Lymphoma / 03.03.2016 Interview with: David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Toronto, ON Canada What is the background for this study? Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance. What are the main findings? Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have "false positive" tests - abnormal findings that are not really cancer. (more…)
Author Interviews, Dental Research, Esophageal, Infections / 02.03.2016 Interview with: Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY What is the background for this study? What are the main findings? Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.  (more…)
Author Interviews, Cancer Research, Diabetes, Diabetologia / 01.03.2016 Interview with: Bendix Carstensen Department of Clinical Epidemiology Steno Diabetes Center Gentofte Medical Research: What is the background for this study? What are the main findings? Response: It has long been known that all diabetes patients have elevated risk of cancer (10-15%). Patients on insulin slightly more (20-25%). Type 1 patients is only a small fraction (10%) of all diabetes patients, but they ALL take insulin. If insulin has a role in cancer occurrence it would be expected to be particularly pronounced in type 1 patients, and increasing by duration. But it is not, the risk of cancer is 15% elevated (if we disregard prostate, breast and other cancers only occurring in one of the sexes), and there is no increase in the excess risk by duration of insulin use. Breast cancer risk is 10% lower and prostate cancer risk some 40% lower. Overall there is very little increased cancer risk - 1% for men 7% for women. (more…)
Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer / 01.03.2016 Interview with Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA What is the background for this study? What are the main findings? Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers. Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. (more…)
Author Interviews, Biomarkers, Cancer Research, Melanoma, Ophthalmology / 01.03.2016 Interview with: J. William Harbour, MD Professor & Vice Chairman Dr. Mark J. Daily Endowed Chair Director, Ocular Oncology Service Bascom Palmer Eye Institute Interim Associated Director for Basic Research Leader, Eye Cancer Site Disease Group Sylvester Comprehensive Cancer Center Member Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Biomedical Research Building, Room 824 Miami FL 33136 Medical Research: What is the background for this study? What are the main findings? Dr. Harbour: Gene expression profiling has become the predominant means of molecular prognostic testing in uveal melanoma, with primary tumors being divided into Class 1 (low metastatic risk, about two thirds of cases) and Class 2 (high metastatic risk, about one third of cases).  In this study, we identified a new biomarker for uveal melanoma that subdivides Class 1 tumors based on the mRNA expression of the oncogene PRAME. Class 1 tumors not expressing PRAME have an extremely low metastatic risk, whereas those expressing PRAME have an intermediate metastatic risk. (more…)
AACR, Author Interviews, Ovarian Cancer, Technology / 29.02.2016 Interview with: Janet A. Sawicki, Ph.D. Deputy Director and Professor Lankenau Institute for Medical Research 100 Lancaster Ave. Wynnewood, PA 19096 What is the background for this study? What are the main findings? Dr. Sawicki: This study addresses the need for a more effective therapy for ovarian cancer. HuR is an RNA-binding protein that is present in high amounts in ovarian tumor cells compared to amounts in normal cells. HuR regulates the expression of thousands of genes that promote the survival of tumor cells. Thus, it is an ideal therapeutic target to suppress ovarian tumor growth. In this study, we used a small interfering RNA (siRNA) to investigate the impact of suppressing HuR expression on ovarian tumor growth in an ovarian cancer mouse model. We made use of the ability to conjugate a novel DNA dendrimer nanocarrier, 3DNA®, to both siHuR and a tumor-targeting moiety to suppress HuR expression specifically in tumor cells following systemic administration while avoiding toxicity in healthy cells. Systemic administration of siHuR-conjugated FA-3DNA to ovarian tumor-bearing mice suppressed tumor growth and ascites development, and significantly prolonged lifespan. Gene expression analysis identified multiple HuR-regulated genes in tumor cells as evidenced by changes in their expression upon HuR inhibition. These HuR-regulated genes function in multiple essential cellular molecular pathways, a finding that sets this therapeutic approach apart from other therapies that target a single gene. (more…)
Author Interviews, Erectile Dysfunction, Prostate, Prostate Cancer, Surgical Research, Urology / 29.02.2016 Interview with: Dr. Pedro Recabal, MD and Memorial Sloan Kettering Cancer Center Department of Surgery, Urology Service New York, NY Urology service, Fundacion Arturo Lopez Perez, Santiago, Chile Dr. Vincent P. Laudone, Memorial Sloan Kettering Cancer Center Department of Surgery Urology Service New York, NY What is the background for this study? Response:  One of the most concerning adverse events that may arise following surgery for prostate cancer (radical prostatectomy) is postoperative erectile dysfunction. The loss of erectile function after surgery is most frequently caused by intraoperative injury to the neurovascular bundles, tiny packages of blood vessels and nerves that conduct the impulses responsible for erection. It is known that if both bundles are removed, patients seldom recover erectile function. Accordingly, neurovascular bundle preservation during Radical prostatectomy has proven benefits in terms of erectile function recovery. However, as these bundles are intimately associated with the posterolateral aspects of the prostate, they must be carefully separated from the surface of the prostate without cutting them, applying excessive traction, or using cautery, all of which could produce irreversible damage and the consequent loss of function. During this dissection, the surgeon risks cutting into the prostatic capsule , which could result in leaving tumor behind. In some cases, the tumor extends beyond the prostate into the neurovascular bundles, and an attempt to preserve these structures could also result in incomplete tumor removal, defeating the purpose of radical prostatectomy. Therefore, many urologists treating patients with “aggressive” tumors (such as the patients in our cohort) would try to avoid leaving cancer behind by removing not only the prostate but also the tissue around it, including the neurovascular bundles. In other words, if you had to chose between removing all the cancer but loosing erectile function, or preserving erectile function but risking an incomplete cancer removal, most patients and surgeons naturally lean towards the first option. Also, in many centers, patients with aggressive prostate cancers are managed with combined treatments (multimodal therapy), by adding hormonal therapy and/or radiotherapy, which could also result in erectile dysfunction. As such, many surgeons believe that there is no rationale for attempting to preserve the neurovascular bundles in these “high-risk” patients because most will end up with erectile dysfunction . However, with the advent of MRI (and integrating other clinical information such as location of the positive biopsies, and intraoperative cues), surgeons can now have a better idea of where the cancer is located, which may aid in surgical planning. For instance, if a tumor is located in the anterior prostate, removing the neurovascular bundles (located on the posterolateral aspects) would provide no oncologic benefit, regardless of the aggressiveness of the tumor. Similarly, if the tumor compromises only the left side, removing the right neurovascular bundle is unlikely to help the patient, but can instead result in harm. Moreover, neurovascular bundle preservation is not an all-or-none procedure; on each side, these bundles can be completely preserved (meaning dissecting exactly along the border between the prostate and the bundle); partially preserved (meaning preserving some of the nerves that are further away from the prostate, and removing the ones that are closer to the prostate); or completely removed along with the prostate (This has been graded in a scale from 1 to 4, where 1 represents complete preservation, and 4 represents complete removal of the neurovascular bundle, with 2 and 3 being partial preservation. This grade is recorded by the surgeon for each side, at the end of the procedure.) As such, sometimes it’s possible to preserve part of the bundle, even if there is a tumor on the same side We designed a retrospective study to look at how high volume surgeons at MSKCC performed radical prostatectomy in high risk patients (how frequently and to what extent where the neurovascular bundles preserved), and what were the outcomes in terms of positive surgical margins (a surrogate for “leaving tumor behind”); use of additional oncologic treatments such as hormone therapy or radiotherapy, and finally, erectile function recovery in patients with functional erections before the operation. The patients in our cohort had at least one NCCN-defined high risk criteria (Gleason score ≥ 8; PSA ≥ 20 ng/ml; Clinical stage ≥ T3). (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, University of Michigan / 28.02.2016 Interview with: Sarah T. Hawley PhD MPH Professor of Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Hawley: Research has shown that breast cancer patients do not have a good understanding of their risk of distant recurrence, and and that the fear of cancer spreading is one of the biggest concerns that patients have. The research that has been done shows that most patients over-esimate this risk, and think they have a bigger chance of the cancer coming back than they actually have. There has been relatively little done to investigate the association between patient over-estimation of risk and patient reported outcomes, specifically their quality of life. We therefore conducted our study to understand the extent of overestimation of risk in a population-based sample of breast cancer patients with very favorable prognosis (DCIS, low risk invasive breast cancer) using a numeric (number based) and descriptive (general understanding) measure, and to understand the association between over-estimation and quality of life. The main findings are that almost 40% of our sample of patients over-estimated their risk; 33% using a numeric measure and 15% using a descriptive measure. There was no clear “type” of patient who overestimated her risk of distant recurrence, though women with lower education more over overestimated numerically than those with higher education. Both numeric and descriptive over-estimation was associated with reduced quality of life outcomes, especially with frequency of worry about recurrence, however over estimating descriptively mattered the most. Women who overestimated their risk both numerically and descriptively had a nearly 10 fold odds of frequent worry compared to women who understood their risk. (more…)
Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016 Interview with: Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia  Medical Research: What is the background for this study? What are the main findings? Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.]. We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007. (more…)