Author Interviews, COVID -19 Coronavirus, JNCI, Johns Hopkins, Respiratory, Vaccine Studies / 22.04.2021 Interview with: Joel N. Blankson, MD, PhD Department of Infectious Diseases Associate Professor Cellular and Molecular Medicine Program Johns Hopkins What is the background for this study? Which vaccines did you evaluate? Response: Prior studies from several groups including our own have found T cell cross-recognition of peptides from SARS-CoV-2 and the common cold coronaviruses. We asked whether as a result of this cross-reactivity, immunization with the SARS-CoV-2 vaccine would also enhance T cell responses to the common cold coronaviruses. Prior studies also suggested that antibodies elicited from the mRNA vaccines had a reduced ability to neutralize the emerging variants of concern. Most of the study participants had received the Pfizer vaccine, but a few had received the Moderna vaccine.  (more…)
Author Interviews, Breast Cancer, Cancer Research, JNCI / 09.11.2018 Interview with: Angela Mariotto PhD Chief of the Data Analytics Branch Surveillance Research Program (SRP) Division of Cancer Control and Population Sciences National Cancer Institute (NCI What is the background for this study? Response: Progressing to metastatic breast cancer (MBC) is one of the major concerns for women diagnosed with early-stage breast cancer. Before our study there were no reliable numbers on risk of metastatic breast cancer recurrence after a (non-metastatic) breast cancer diagnosis, as registries do not routinely collect this data. (more…)
Author Interviews, Colon Cancer, JNCI, NIH, Vitamin D / 09.07.2018 Interview with: Stephanie J. Weinstein, M.S., Ph.D.  Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics National Cancer Institute, NIH What is the background for this study?   Response: Vitamin D, known for its role in maintaining bone health, is hypothesized to lower colorectal cancer risk via several pathways related to cell growth and regulation. Previous prospective studies have reported inconsistent results for whether higher concentrations of circulating 25-hydroxyvitamin D, the accepted measure of vitamin D status, are linked to lower risk of colorectal cancer. The few randomized clinical trials of vitamin D supplementation and colorectal cancer completed thus far have not shown an effect; but study size, relatively short supplementation duration, and only moderate compliance may have contributed to their null findings. To address inconsistencies in prior studies on vitamin D, and to investigate associations in population subgroups, we harmonized and analyzed participant-level data from over 5,700 colorectal cancer cases who had blood collected before colorectal cancer diagnosis, and 7,100 matched cancer-free controls. Study participants were drawn from 17 prospective cohorts from the United States, Europe, and Asia and were followed for an average of 5.5 years (range: 1 – 25 years). We used a single, widely accepted assay and laboratory for new vitamin D measurements and calibrated existing vitamin D measurements. In the past, substantial differences between assays made it difficult to integrate vitamin D data from different studies. Our novel calibration approach enabled us to explore risk systematically over the broad range of vitamin D levels seen internationally.  (more…)
Author Interviews, Breast Cancer, JNCI, UT Southwestern / 16.04.2018 Interview with: Yingfei Wang, Ph.D. and Weibo Luo, Ph.D. Department of Pathology UT Southwestern Medical Center Dallas TX 75390 What is the background for this study? Response: Breast cancer is the most commonly diagnosed cancer in women. Tumor metastasis is frequently found in breast cancer patients and causes more than 90% of cancer death. There is currently no cure for this deadly disease. We have known that breast tumor is not supplied with sufficient oxygen (a phenomenon known as hypoxia), which makes breast cancer cells more aggressive and may be responsible for tumor recurrence, metastasis, and therapy resistance. Hypoxia-inducible factor (HIF) is a master regulator frequently detected in the hypoxic regions and switches on many oncogenes needed for breast cancer cells to grow and spread around the body. The role of HIF in gene regulation is precisely controlled and shutting down of HIF’s activity would be a promising strategy for the treatment of metastatic breast cancer. (more…)
Author Interviews, JNCI, Lung Cancer, UT Southwestern / 04.04.2018 Interview with: Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center What is the background for this study? Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR.  (more…)
Author Interviews, JNCI, Mental Health Research, Pharmacology, UT Southwestern, Weight Research / 23.08.2017 Interview with: Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077 What is the background for this study? Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma. On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief. (more…)
Author Interviews, JNCI, Lung Cancer, Smoking, Tobacco, Tobacco Research / 22.05.2017 Interview with: Peter G. Shields, M.D. Deputy Director, Comprehensive Cancer Center James Cancer Hospital Professor, College of Medicine Julius F. Stone Chair in Cancer Research The Ohio State University Columbus, OH What do we know about the health effects of cigarette filters?  Response:  The issue is that the design of the filters makes a cigarette even more dangerous, which can be regulated by the FDA. The issue is not about having a filter, but how they are made. And now we are changing the dialogue to the design of virtually all cigarettes. The holes on the filter are likely one reason the cigarettes of today are more dangerous. (more…)
Author Interviews, Cancer Research, JNCI / 20.12.2016 Interview with: Theodore Brasky, PhD The Ohio State University Comprehensive Cancer Center What is the background for this study? What are the main findings? Response: There is a significant amount of data to suggest that long-term, regular use of nonsteroidal anti-inflammatory drugs (NSAIDS; examples include aspirin and ibuprofen) are associated with reduced risks of several cancers. Although the data across studies are inconsistent, one such candidate is endometrial cancer, which is the most common gynecologic cancer. There is good evidence that the use of these medications is associated with improved prognosis among patients diagnosed with colon cancer. Despite the importance of inflammation in endometrial cancer progression, very few have examined whether use of NSAIDs is associated with risk of death or recurrence from the disease. The study we published is the first of its kind to examine NSAID use comprehensively and in a study of over 4,000 patients. (more…)
Author Interviews, Cancer Research, JNCI, Toxin Research / 14.05.2016 Interview with: Dr. Debra Silverman Sc.D Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics National Cancer Institute What is the background for this study? What are the main findings? Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor. A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:
  • Naturally occurring arsenic from geological sources (released from rock deep in the earth)
  • Leaching of arsenic-based pesticides used on food crops many years ago. From the 1920s through the 1960s there was extensive agricultural use of arsenic-based pesticides. These compounds were used on food crops such as blueberries, apples and potatoes. Residue from the treatments may have leached into the ground water.
Intake of water containing high levels of arsenic is an established cause of bladder cancer, largely based on studies conducted in highly exposed populations. However, emerging evidence suggests that low-to-moderate levels of exposure may also increase bladder cancer risk. To explore possible reasons for the excess incidence of bladder cancer in northern New England, we conducted a large, comprehensive population-based case-control study in Maine, New Hampshire and Vermont. We examined the role of known and suspected bladder cancer risk factors, with a focus on private well water consumption and arsenic levels in drinking water. The major cause of bladder cancer is cigarette smoking. Some occupational exposures (e.g., exposure to metalworking fluids such as that experienced by metalworkers and some types of machine operators) are also associated with elevated risk. However, smoking and occupational exposures do not appear to explain the New England bladder cancer excess. This study was funded and carried out by researchers in the NCI Division of Cancer Epidemiology and Genetics in collaboration with the Geisel School of Medicine at Dartmouth, the Departments of Health for Maine, New Hampshire, and Vermont, and the US Geological Survey. We reported that heavy consumption of drinking water from private dug wells (which are shallow—less than 50 feet deep—and susceptible to contamination from manmade sources than drilled wells), established prior to 1960 (when arsenic-based pesticides were widely used), may have contributed to the longstanding bladder cancer excess in northern New England. We saw that cumulative arsenic exposure from all water sources showed an increasing risk with increasing exposure (exposure-response relationship). Among the highest exposed participants, risk was twice that of the lowest exposure group. (Cumulative arsenic exposure is a measure of the average daily arsenic intake by number of days of arsenic exposure.) (more…)
Author Interviews, Cancer Research, Hepatitis - Liver Disease, HPV, JNCI, MD Anderson / 15.04.2016 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, 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, Genetic Research, JNCI, Melanoma / 21.02.2016 Interview with: Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599 Medical Research: What is the background for this study? Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways. Medical Research: What are the main findings? Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development. (more…)
Author Interviews, Breast Cancer, Depression, JNCI, Kaiser Permanente / 03.12.2015 Interview with: Reina Haque, PhD, MPH Research scientist Department of Research & Evaluation Kaiser Permanente Southern California Pasadena Calif Medical Research: What is the background for this study? What are the main findings? Dr. Haque: Tamoxifen is a commonly prescribed generic drug taken by women with breast cancer to reduce their chances of developing a recurrence. Tamoxifen is recommended for five years, but has notable side effects, including hot flashes, night sweats and depression. Since hormone replacement therapy is not recommended to alleviate these symptoms in breast-cancer survivors, antidepressants have been increasingly prescribed for relief. Almost half of the 2.4 million breast-cancer survivors in the U.S. take antidepressants. However, previous studies have suggested that antidepressants reduce tamoxifen's effectiveness in lowering subsequent breast-cancer risk. This study was conducted to determine whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, JNCI, Mayo Clinic, Race/Ethnic Diversity / 05.10.2015

Harry H. Yoon, MD Mayo Clinic Rochester, MN Interview with: Harry H. Yoon, MD Mayo Clinic Rochester, MN 55905 Medical Research: What is the background for this study? What are the main findings? Dr. Yoon: In the U.S., the survival of patients with colon cancer is known to differ by race, with individuals of black race having worse outcomes than those of white race. However, it has been difficult to tease apart why the differences in survival exist. It is generally believed that social or other non-biologic factors (eg, decreased access to care, suboptimal treatment) contribute to the discrepancy.  It’s also known that differences in the general medical condition of patients could affect how long a patient lives. However, it is unknown whether there are race-based differences in the biology of colon tumors themselves.  This biology can be reflected in the genetic composition of tumors, as well as by whether and how quickly the cancer returns after the patient has undergone surgery and chemotherapy. In addition, it is unknown whether race-based differences in biology may be related to the age of the patient at the time of diagnosis.  Blacks with colorectal cancer typically have an earlier age of onset than whites do. A major barrier to addressing these questions are that there are very few large populations of colon cancer patients where everyone had the same disease stage and received uniform treatment, and where patients were monitored for years afterward specifically to see whether the cancer returned.  It is much harder to measure whether cancer has returned (ie, cancer recurrence), as compared to simply knowing whether a patient is alive or dead.  This difference is important, because knowing about cancer recurrence sheds more light on cancer biology than only knowing about patient survival, since many factors unrelated to cancer biology (eg., heart disease) can affect whether a person is alive or dead. The most reliable data on cancer recurrence (not just patient survival) generally comes from patients who have enrolled in a clinical trial.  In the Alliance N0147 trial, all patients had the same cancer stage (ie, stage III), underwent surgery and received standard of care chemotherapy (ie, “FOLFOX”) after surgery.  Patients had uniform, periodic monitoring after chemotherapy to see if the cancer returned. In other words, examining racial outcomes in this cohort largely eliminates some of the key factors (eg, decreased access to care, suboptimal treatment) that are believed to contribute to racial discrepancies, and provides a unique opportunity to determine if differences in cancer biology between races may exist. This study was done to see if colon cancers are genetically different based on race, and whether race-based differences exist in cancer recurrence rates. The study found that tumors from whites, blacks, and Asians were different in terms of the frequency of mutations in two key cancer-related genes, BRAF and KRAS.  Tumors from whites were twice as likely to have mutated BRAF (14% in whites compared to 6% in Asians and 6% in blacks).  Tumors from blacks had the highest frequency of KRAS mutations (44% in blacks compared to 28% in Asians and 35% in whites).  Tumors from Asians were the mostly likely to have normal copies of both genes (67% in Asians compared to 50% in blacks and 51% in whites). Next, the study found that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites.  However, this discrepancy was only evident among young patients (ie, aged less than 50 years).  Almost 50% of younger black patients experienced colon cancer recurrence within 5 years, compared to ~30% of black patients over age 50, or compared to white or Asian patients regardless of age. The worse outcome among young blacks remained evident even after adjusting for many potential confounding factors, such as tumor grade, the number of malignant nodes, or the presence of BRAF or KRASmutations.  Because this question was examined in a clinical trial cohort of uniform stage and treatment, the role of multiple important potential confounders was diminished. To our knowledge, this is the first report indicating that colon cancers from young black individuals have a higher chance of relapsing after surgery and chemotherapy, compared to those from white individuals. (more…)
Author Interviews, Breast Cancer, JNCI / 21.09.2015

Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD Interview with: Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892  Medical Research: What is the background for this study? What are the main findings? Dr. Rosenberg: It has been previously reported that breast cancer burden (number of new cases diagnosed in a year) is expected to rise in the future, mostly due to the aging of the female population in the US. Also, it has been established that the age-adjusted breast cancer incidence rates (cases per 100,000 women per year) are increasing for invasive ER-positive cancers overall and decreasing for ER-negative cancers overall. When taken together, these two trends tend balance each other out, resulting in a somewhat flat breast cancer incidence rate overall.  Though the overall trends for invasive breast cancer have been previously reported, this study uses a more refined forecasting method by including recent birth cohort patterns to forecast breast cancer to 2030 by age group, estrogen receptor-status, and invasive vs. in situ tumors. New in this report are the findings for in situ tumors and the more granular break down by age, ER status, and invasive vs. in situ tumors both for rate and burden (number of cases). (more…)
Author Interviews, Cancer Research, JNCI / 08.07.2015

Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 Interview with: Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 Australia Medical Research: What is the background for this study? Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome. A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome. (more…)
Author Interviews, Cancer Research, JNCI, NIH, OBGYNE / 02.07.2015 Interview with: Ashley S. Felix, PhD Bethesda, MD MedicalResearch: What is the background for this study? What are the main findings? Dr. Felix: Endometrial cancer prognosis is strongly affected by disease stage, or the extent of spread from the primary site. Endometrial cancers can spread via the lymph nodes, blood vessels, through the uterine wall, or through the fallopian tube into the peritoneal cavity. The last of these mechanisms is poorly understood, but appears to be a more common mode of spread for aggressive histologic subtypes of endometrial cancer. We hypothesized that women who previously underwent tubal ligation (TL) and later developed endometrial cancer would have lower stage disease, possibly by blocking passage of tumor cells along the fallopian tubes. Further, we hypothesized that TL would be associated with better prognosis, due to its relationship with lower stage. We found that women in our study who previously had tubal ligation were more likely to have lower stage endometrial cancer compared with women who did not report a previous tubal ligation. Specifically, tubal ligation was inversely associated with stage III and stage IV cancer across all subtypes of the disease, including aggressive histologic subtypes. Further, in statistical models of tubal ligation, tumor stage, and mortality, we observed no independent association with improved survival, suggesting that tubal ligation impacts mortality mainly through its effects on stage. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, JNCI / 30.06.2015

Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts Interview with: Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114 MedicalResearch: What is the background for this study? What are the main findings? Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting. We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical models of spontaneous lymphatic metastasis, however there were no mechanistic data to explain these observations. Here, we developed a novel chronic lymph node window model to facilitate new discoveries in the mechanisms of growth and spread of lymph node metastases. Our new data provide pre-clinical evidence along with supporting clinical evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in adjuvant setting, particularly those involving lymph node metastases. (more…)
Author Interviews, Cancer Research, Chemotherapy, JNCI, MD Anderson, Ovarian Cancer / 26.05.2015

Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas Interview with: Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Zhang: Epithelial ovarian cancer remains the most lethal gynecological malignancy. The 5-year survival rate for patients with advanced ovarian cancer is only 30-40%, and acquired resistance to platinum is considered a major factor in disease relapse. A major challenge in cancer treatment is the resilient ability of cancer cells to repair DNA damage caused by chemotherapy agents.  In this study, we found that adding a molecule called miR-506 to standard chemotherapy can help cells overcome drug resistance, so that the chemotherapy drugs remain effective against ovarian cancer. This research supports a new combination approach, which may substantially benefit patients with this deadly disease. (more…)
Author Interviews, Breast Cancer, JNCI, Surgical Research / 11.05.2015

Bernadette A.M. Heemskerk-Gerritsen, Ph.D.		 Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the Interview with: Bernadette A.M. Heemskerk-Gerritsen, Ph.D. Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Heemskerk-Gerritsen: Women with a BRCA1 or BRCA2 mutation have substantially higher risks of developing both primary and contralateral breast cancer (BC) and ovarian cancer than women from the general population. Options to reduce these increased cancer risks include risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). The latter intervention obviously reduces the risk of developing ovarian cancer, but has been reported also to reduce the risk of developing a subsequent breast cancer with approximately 50%. However, studies on the efficacy of risk-reducing surgery in BRCA1/2 mutation carriers are confined to observational studies, thus challenging several methodological issues. Consequently, previous studies on breast cancer risk-reduction after RRSO may have been influenced by bias associated with selection of study subjects, bias associated with start of follow-up, or by confounding, and breast cancer risk-reduction may have been overestimated. In the current study, we revisited the association between risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1/2 mutation carriers, focusing on the impact of different analytical methods and potential types of bias. First, we replicated the analyses of four previously performed studies, to examine if our Dutch cohort was comparable with the cohorts used in the previous studies. We replicated the approximately 50% breast cancer risk reduction after RRSO in the Dutch cohort. Second, we estimated the effect of RRSO on breast cancer risk in the Dutch cohort using a revised analytical approach for observational studies in BRCA1/2 mutation carriers in order to minimize bias as much as possible. Using this method of analysis, we found no evidence of first BC risk-reduction after RRSO in BRCA1/2 mutation carriers. (more…)
Author Interviews, Breast Cancer, Cancer Research, Cognitive Issues, JNCI / 19.04.2015

Dr. Kerstin Hermelink Senior psychologist  Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Interview with: Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Munich MedicalResearch: What is the background for this study? What are the main findings? Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all. Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained. Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis. We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms. Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer. (more…)
Author Interviews, Coffee, JNCI, Melanoma, NIH, Yale / 21.01.2015 Interview with: Erikka Loftfield Doctoral student at the Yale School of Public Health Fellow at the National Cancer Institute Medical Research: What is the background for this study? What are the main findings? Response: Previous studies have reported conflicting results on the association between coffee drinking and melanoma. We sought to clarify this relationship using data from the large NIH-AARP Diet and Health Study. We followed over 400,000 retirees aged 50 to 71 years at study entry for an average of 10 years. Participants were asked to report typical coffee intake. During the course of follow-up nearly 3,000 cases of malignant melanoma occurred. In our study, we observed that individuals who reported the highest total coffee intake (4 cups/day) had about 20% lower risk of malignant melanoma compared with those who did not consume coffee. (more…)
Author Interviews, Breast Cancer, JNCI / 11.01.2015 Interview with: Hazel B. Nichols, PhD Assistant Professor, Department of Epidemiology University of North Carolina Gillings School of Global Public Health MedicalResearch:What is the background for this study? Dr. Nichols: Tamoxifen, a drug that is often used to treat breast cancer, has also been approved to prevent breast cancer in women who may be at high risk for developing the disease. Taking tamoxifen for 5 years can lower breast cancer risk by up to 48%. The United States Federal Drug Administration (FDA) approved tamoxifen for breast cancer prevention more than 15 years ago (in 1998) for women ages 35 and older who are at high risk of breast cancer and who are at low risk for serious side effects. National estimates show that <1% of women who are eligible to use tamoxifen actually use it for breast cancer prevention. While tamoxifen lowers breast cancer risk it does cause hot flashes and may lead to serious side effects such as cataract, stroke, and uterine cancer. Women who start taking tamoxifen may also stop taking it before the recommended 5-years due to side effects. We used a tool developed by scientists at the National Cancer Institute (NCI) to calculate whether the benefits of tamoxifen outweighed the risks for women in the Sister Study, a study of more than 50,000 U.S. and Puerto Rican women with a family history of breast cancer. The tool uses information on a woman’s age, race, breast cancer risk, menopausal status, and whether she had a hysterectomy (surgical removal of the uterus) to estimate whether there is no, moderate or strong evidence that the benefits of tamoxifen will outweigh the risks. (more…)
Author Interviews, Breast Cancer, JNCI / 21.12.2014 Interview with: Dr Ranjit Manchanda Consultant Gynaecological Oncologist, St Bartholomew’s Hospital, London, UK Honorary Sr Lecturer, Women’s Cancer, EGA Institute for Women's Health, University College London, UK  and Professor Ian Jacobs Vice President, The University of Manchester Dean & Head School of Medicine Faculty of Medical & Human Sciences, Director MAHSC (Manchester Academic Health Science Centre) Medical Research: What is the background for this study? What are the main findings? Dr. Jacobs:  Background- Women carrying a BRCA1/2 gene alteration have a very high risk of developing breast and ovarian cancer and men carrying this alteration have an increased risk of prostate and breast cancer. Approximately 45-65% women who have this inherited genetic change will develop breast cancer and 15-35% ovarian cancer. They also have a 50% chance of passing these genes on to their children. At risk individuals can access available options of screening and prevention through the National Health Service (NHS). Some population groups across the world are known to have a higher frequency of BRCA 1/2 gene alterations than others. One example is Ashkenazi Jews who have a 1 in 40 likelihood of having a BRCA1/2 gene alteration. This is 10-20 times higher than in the general non-Jewish population. At present in the UK, genetic testing is available within the NHS to individuals who have a strong family history of cancer. However, many people are not aware of their family history or its significance and do not seek advice. Many other individuals with BRCA1/2 gene alterations do not have a family history at all. The current approach misses a large number of people at risk who could benefit from knowing about their BRCA 1/2 mutation status and the ability to access opportunities for prevention or screening. In order to address this the GCaPPS study has investigated the best method of screening for risk of inherited (familial) cancer by exploring the alternative approach of offering the genetic test to all men and women >18 years in the Ashkenazi Jewish population. It does so by comparing the benefits and disadvantages of: (i) The current system of testing only those with a family history and (ii) The new option of testing everyone in the population. Main Findings: Over half of the BRCA1/BRCA2 carriers detected did not give a strong family history of cancer and would not have been identified by current family history based testing criteria used in the NHS (National Health Service) in the UK and most health systems internationally. Reassuringly population-based genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life. A health economic analysis indicated that population-based screening for BRCA-mutations in Ashkenazi Jewish women ≥30years would be highly cost-effective compared to the traditional family history based approach. Such an approach if implemented could reduce the incidence of and deaths from breast and ovarian cancer as well as reducing cost and save the NHS funds. (more…)
Author Interviews, Breast Cancer, JNCI, Mayo Clinic / 14.12.2014

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo Interview with: Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Dr. Goetz: There has been conflicting data with regard to the importance of tamoxifen metabolism as measured by CYP2D6 genetic variation.   Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy.   Our findings demonstrated that these studies were flawed in part based on analytical validity issues.  In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples. (more…)
Author Interviews, Cancer Research, JNCI, Lung Cancer, UT Southwestern / 02.10.2014

Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical Interview with: Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical Center Medical Research: What are the main findings of the study? Dr. Gerber: Fewer than 3% of adult cancer patients in the United States are enrolled in clinical trials.  Increasingly numerous and stringent eligibility criteria are a major factor limiting participation in clinical trials.  We examined the longstanding and widespread practice of excluding patients with prior cancer from oncology clinical trials.  This policy presumably reflects concerns that a prior cancer would interfere with the conduct, outcomes, or interpretation of a clinical trial, although there is no clear evidence supporting that assumption. We examined more than 50 National Cancer Institute (NCI)-sponsored lung cancer clinical trials.  We found that 80% excluded patients with prior cancers.  This exclusion criterion was applied broadly, including to more than two-thirds of trials with non-survival endpoints.  We then examined national Surveillance Epidemiology and End Results (SEER)-Medicare linked data to estimate the proportion of patients who would be excluded from these trials due to prior cancer.  We found that up to 18% of potential patients are excluded for this reason alone.  In large phase 3 clinical trials, that corresponds to more than 200 patients. (more…)
Author Interviews, JNCI, Weight Research / 25.07.2014

Sean Davies PhD Department of Pharmacology Vanderbilt Interview with: Sean Davies PhD Department of Pharmacology Vanderbilt University Medical Research: What are the main findings of the study? Dr. Davies: N-acyl phosphatidylethanolamine (NAPE) is a fat-like molecule normally produced by small intestine of mammals in response to eating high fat foods that helps signal a feeling of fullness to the brain.  This sensation of fullness is what normally helps us decide to stop eating, but in obese people it appears that not enough NAPE is produced so that not enough of that signal gets sent to the brain.  So we wanted to find a way to increase the amount of NAPE made in the intestinal tract, with the hope that this would help protect against obesity. Our approach was to engineer a probiotic bacteria that normally colonizes the gut of humans and other mammals so that it would make NAPE.  Our hope was that when this gut bacteria made the NAPE, it would be absorbed by the intestine and help supplement the NAPE already being made by the intestine so that a more complete sensation of fullness would be send to the brain. What we found was that our engineered bacteria made a significant amount of NAPE and that when fed to mice, the bacteria would colonize the gut like normal and that the intestinal cells could absorb this NAPE.  Most importantly, we found that mice that received this bacteria ate less of the high fat diet than mice that were not treated or that received bacteria that did not make NAPE. Because the mice ate less of the high fat diet, and also because they burned the fat they had more effectively, the mice receiving the bacteria producing NAPE had only 50% of  the body fat of the control mice.  While the control mice showed the early signs of developing diabetes, the mice that received the NAPE producing bacteria showed almost no signs of developing diabetes. So the presence of these NAPE producing bacteria protected the mice from the harmful effects of the high fat diet. Another key findings was that because the bacteria live in the GI tract and keep producing the NAPE for many weeks, we didn’t have to keep administering the bacteria to the mice to keep up the protective effect.  Even a month after we stopped giving the bacteria producing NAPE, the mice were still protected from the effects of the high fat diet.  Eventually after about six weeks, the bacteria died out and the mice started eating the same amount of food as the control mice, but even for at least another six weeks after this, they still weighed less than the control mice. (more…)
Author Interviews, Breast Cancer, JNCI, MD Anderson, Weight Research / 02.07.2014

Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine The University of Texas MD Anderson Cancer Center Department of Emergency Medicine Department of Endocrine Neoplasia & Hormonal Disorders Houston, Texas Interview with Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine The University of Texas MD Anderson Cancer Center Department of Emergency Medicine Department of Endocrine Neoplasia & Hormonal Disorders Houston, Texas  77230-1402 MedicalResearch: What are the main findings of the study? Dr. Yeung: We believe that this study has bridged a significant gap in knowledge between epidemiological data (the association of obesity and poor breast cancer prognosis) and biological mechanisms mediating the impact of obesity on cancer. This study provides an important mechanistic insight into the causal relationship between obesity and breast cancer growth.
  1. Direct evidence for the links between obesity-associated changes in the biological processes and hallmarks of cancer in human estrogen receptor-positive (ER+) breast cancer. 
It is well known that obesity is associated epidemiologicaly with decreased survival in ER+ breast cancer patients. Although a body of experimental literature exists to suggest important roles for estrogen, insulin/IGF-1 and adipokine signaling and inflammation in the mechanisms mediating the impact of obesity on cancer, direct evidence for these mechanisms and their importance relative to one another is lacking in cancers from obese humans. Functional transcriptomic analysis of a prospective observation cohort with treatment-naïve ER+ breast cancer samples identified the insulin/PI3K signaling and secretion of cytokines among the top biological processes involved. Many of the obesity-associated changes in biological processes can be linked to cancer hallmarks.  Upstream regulator analysis identified estrogen (?-estradiol), insulin (INS1), insulin-like growth factor-1 (IGF1), and adipokines [vascular endothelial growth factor A (VEGFA), tissue necrosis factor (TNF), interleukin-6 (IL6), oncostatin-M (OSM), chemokine ligand 5 (CCL5), leptin (LEP), leukemia inhibitory factor (LIF), C-reactive protein (CRP), adiponectin (ADIPOQ), and interleukin-10 (IL10)] in mediating the impact of obesity on human ER+ breast cancer.
  1. Experimental evidence that obesity causes accelerated oncogene-driven ER+ breast cancer carcinogenesis.
While it is not possible to conduct a human experiment to prospectively examine the causal relationship between obesity and breast cancer, we created a transgenic mouse model with genetically induced obesity and oncogene-driven breast cancer.  With this model we found strong in vivo evidence using both longitudinal experiments and cross-sectional experiments that obesity accelerated oncogene-driven breast carcinogenesis. (more…)
Author Interviews, Colon Cancer, JNCI / 01.07.2014

Kaspar Truninger, MD, FMH Gastroenterology and Internal Medicine Langenthal, Interview with: Kaspar Truninger, MD, FMH Gastroenterology and Internal Medicine Langenthal, Switzerland MedicalResearch: What are the main findings of the study? Dr. Truninger: In our study, we investigated the effect of lifestyle exposure on DNA methylation. We measured genome-wide promoter CpG methylation in 1092 normal colon biopsies from 546 healthy females. We observed that fewer CpGs acquired age-dependent methylation in users of aspirin and hormonal replacement therapy compared with nonusers, whereas more CpGs were affected in smokers and individuals with a body mass index > 25 compared with nonsmokers and less obese females. Half of the CpGs showing age-dependent methylation gain were hypermethylated in tissue of colorectal cancer. These loci gained methylation with a higher rate and were particularly susceptible to lifestyle exposure compared to age-only methylated CpGs. In addition, these CpGs were enriched for polycomb regions.  Finally, all effects were different according to the anatomic location along the colon. (more…)