Author Interviews, Cancer Research, Radiology / 29.12.2014

Ulas Sunar, Ph.D. Research Assistant Prof. Dept of Biomedical Engineering SUNY-University at BuffaloMedicalResearch.com Interview with: Ulas Sunar, Ph.D. Research Assistant Prof. Dept of Biomedical Engineering SUNY-University at Buffalo Medical Research: What is the background for this device? What are the main implications? Dr. Sunar: Most of ovarian cancer cases are not diagnosed until after the disease has spread in the abdominal cavity. A major challenge is to detect and remove dozens or hundreds of metastatic tumor nodules within the abdominal cavity. Fluorescence endoscopy can utilize the high sensitivity and specificity of fluorescence contrast and high resolution of endoscopic imaging. We are developing a clinically-relevant, fiber-based endoscopy system that allows both accurate fluorescence imaging and for projecting adaptive-shaped light for light-induced chemodrug delivery. The system can provide high contrast for improved demarcation and trigger drug release to destroy micrometastases. The system utilizes a highly sensitive camera and structured light illumination scheme with a projector for accurate fluorescence imaging of drug distribution, as well as allows light-triggered drug release and adaptive light delivery for optimized treatment of micrometastases. We expect that our novel illumination and drug release strategy will permit lower doxorubicin doses to be administered while simultaneously achieving more specific drug delivery in order to destroy the micrometastases and improve survival rates.
Author Interviews, Breast Cancer / 29.12.2014

Dr. SikovMedicalResearch.com Interview with: William M. Sikov, MD Associate Chief of Clinical Research Program in Women's Oncology Women & Infants Rhode Island Associate professor of Medicine The Warren Alpert Medical School of Brown University Medical Research: What is the background for this study? What are the main findings? Dr. Sikov: The data presented at San Antonio this year are the first results from correlative studies performed on pretreatment tissue samples from patients treated on CALGB 40603, a 2 x 2 factorial randomized phase II study which tested the addition of carboplatin or bevacizumab to a standard neoadjuvant chemotherapy regimen consisting of weekly paclitaxel followed by dose-dense AC in patients with stage II-III triple breast cancer. Last year at San Antonio (and subsequently published in the JCO) we presented the primary endpoint of the study - pathologic complete response (pCR) - and reported that the addition of either carboplatin or bevacizumab significantly increased pCR rates compared to the control regimen. This year we reported results of a preplanned analysis which assessed the impact of intrinsic subtype (based on mRNA expression analysis) - especially the basal-like subtype - on the impact of the two agents on pCR rates. We also reported the effects of a number of previously published mRNA expression signatures on pCR rates and the benefits of adding carboplatin or bevacizumab. The findings reported were as follows: We had a higher percentage of basal-like cancers than we anticipated when the study was designed (87% vs. 70-80% expected), which we hypothesize is due to improvements in the ways we assess hormone receptor and HER2 status, and thus define triple-negative breast cancer, compared to 10-15 years ago. When we limit our analysis to the subset of patients with basal-like cancers, we continue to see a statistically significant increases in pCR rates with both carboplatin and bevacizumab. However, while the 13% of patients with non-basal-like cancers get essentially the same increase in pCR rates with carboplatin as do the basal-likes, non-basal-likes actually had a reduction in their pCR rates with the addition of bevacizumab - thus, there was a significant interaction between subtype and pCR benefit for bevacizumab but not for carboplatin. Among the mRNA signatures we assessed, higher expression of immune signatures  (indicating more tumor-infiltrating lymphocytes) correlated with higher pCR rates, but not greater pCR increments with either carboplatin or bevacizumab. Higher proliferation, lower estrogen, and higher TP53 mutation signaturss also correlated with higher pCR rates overall, and also with greater pCR increments with bevacizumab, but not carboplatin.
Author Interviews, Breast Cancer, Johns Hopkins, Journal Clinical Oncology, Leukemia / 28.12.2014

MedicalResearch.com Interview with: Dr. Judy Karp, Dr. Antonio Wolff and  Dr. Kala Visvanathan Breast Cancer Program Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, MD 21287 Medical Research: What is the background for this study? What are the main findings? Response: The background for this study was the clinical observation from the Johns Hopkins Leukemia Program that a significant number of women with newly diagnosed acute myeloid leukemia had a personal history for breast and/or ovarian cancers.  This observation led to our examination of the large NCCN breast cancer database in a multidisciplinary and multi-institutional study.  The overarching finding in our study is that the risk of developing some form of leukemia following chemotherapy with or without radiation therapy, while small, continues to increase over at least 10 years without a plateau and is roughly twice what we thought it to be from previous breast cancer studies.
Author Interviews, Breast Cancer, JNCI / 21.12.2014

MedicalResearch.com 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.
Breast Cancer / 20.12.2014

Thomas Rogers PhD Candidate- Cancer Biology Graduate Program Laboratory of Jennifer Richer Department of Pathology University of Colorado-Anschutz Medical Campus Laboratory of CU Cancer Center investigator, Jennifer Richer, PhD.MedicalResearch.com Interview with: Thomas Rogers PhD Candidate- Cancer Biology Graduate Program Laboratory of Jennifer Richer Department of Pathology University of Colorado-Anschutz Medical Campus Laboratory of CU Cancer Center investigator, Jennifer Richer, PhD. Medical Research: What is the background for this study? What are the main findings? Response: Background: Survival while detached from a basement membrane is a critical trait of cancer cells progressing through the metastatic cascade. This is particularly important for the triple-negative breast cancer (TNBC) subtype, which lacks estrogen and progesterone receptors and does not have amplification of HER2, and has a peak risk of recurrence within the first three years post-diagnosis. Triple-negative breast cancer also has the highest mortality rate in the first five years as compared to other breast cancer subtypes. We performed global profiling of TNBC cells in adherent versus forced suspension culture conditions after24 hours. These data revealed that triple-negative breast cancer cells surviving in suspension upregulate multiple genes involved in tryptophan catabolism, also known as the kynurenine pathway, including the rate limiting enzyme tryptophan 2,3,-dioxygenase (TDO2) and kynureninase (KYNU). Kynurenine, a key intermediate metabolite of this pathway activates the aryl hydrocarbon receptor (AhR), which was also up-regulated in TNBC cells grown in forced-suspension culture. Main Findings: Critical enzymes of the kynurenine pathway, TDO2 and KYNU, are upregulated in triple-negative breast cancer cells grown in forced-suspension culture. Furthermore, secreted kynurenine doubles in TNBC cells in forced-suspension culture as measured by high performance liquid chromatography (HPLC). Kynurenine activates the aryl hydrocarbon receptor in triple-negative breast cancer cells grown in forced-suspension culture. Targeting TDO2 and AhR with small molecule inhibitors or short hairpin RNAs decreased survival in suspension, migration/invasion, and proliferation of TNBC cells. Lastly, TDO2 gene expression is higher in invasive ductal breast carcinoma as compared to normal breast tissue and is significantly higher in estrogen receptor negative tumors as compared to estrogen receptor positive tumors. In addition, patients with higher (above-median) TDO2 expression in their primary tumor had significantly shorter overall survival than those with low TDO2. Conclusions: The kynurenine pathway is activated in TNBC cells in forced suspension and facilitates the invasive/metastatic phenotype of this aggressive breast cancer subtype. Our findings support further investigations into targeting the enzyme TDO2 in TNBC as a novel therapeutic strategy with potential to reduce TNBC mortality rates. Kynurenine is well-known to suppress immune cell function via activation of AhR.
Author Interviews, Cancer Research, Nature / 19.12.2014

Dr Catherine Olsen | Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029MedicalResearch.com Interview with: Dr Catherine Olsen  |  Senior Research Officer QIMR Berghofer Medical Research Institute Royal Brisbane Hospital, QLD 4029 Medical Research: What is the background for this study? What are the main findings? Response: Squamous cell carcinomas (SCCs)are the second most common skin cancer occurring in white skinned populations. They cause significant morbidity as they can invade local structures (often the nose or ears) and they also have the potential to metastasize although most are successfully treated before any spread occurs. They are also very expensive cancers to treat because they are so common, posing a significant burden on health care budgets. NSAIDS have been shown to be protective for other cancers (e.g. colorectal and oesophageal cancer). This prompted use to evaluate all of the available evidence on NSAIDs use and SCC by conducting a systematic review and meta-analysis of the association.
Author Interviews, Dermatology, JAMA, Melanoma, Occupational Health, UCSF / 18.12.2014

Martina Sanlorenzo, MD Department of Dermatology Mount Zion Cancer Research Center University of California, San FranciscoMedicalResearch.com Interview with: Martina Sanlorenzo, MD Department of Dermatology Mount Zion Cancer Research Center University of California, San Francisco Medical Research: What is the background for this study? Dr. Sanlorenzo: We recently performed a meta-analysis and found an increased risk of melanoma in pilots and cabin crew. One of the possible occupational hazards responsible for this risk is UV radiation. Medical Research: What are the main findings? Dr. Sanlorenzo: We performed UV measurements in airplane cockpits during flight and we found that windshields blocked UV-B but allowed UV-A transmission. We compared the UV-A dose in airplanes with the UV-A dose in tanning beds, whose use is a known risk factor for melanoma. Pilots flying for 56.6 minutes at 30,000 feet received the same amount of UV-A carcinogenic effective radiation of a 20-minute tanning beds session.
Author Interviews, Colon Cancer, Erasmus / 17.12.2014

MedicalResearch.com Interview with: Reinier G.S. Meester, M.Sc Department of Public Health, ErasmusMC, Rotterdam, Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Despite decreasing death rates from colorectal cancer over the past decades, it still ranks as the second leading cause of cancer deaths in the U.S. Screening for colorectal cancer is highly effective, but only 58% of the eligible population reported up-to-date with screening. This suggests that a substantial proportion of current colorectal cancer deaths in the U.S. are avoidable. We found that approximately 60% (32,200 deaths) of current deaths from colorectal cancer may be due to not receiving screening.
Author Interviews, Breast Cancer, University of Pittsburgh / 17.12.2014

Dr. Ryan Hartmaier PhD Postdoctoral Associate Magee-Womens Research Institute (MWRI) and the University of Pittsburgh Cancer InstituteMedicalResearch.com Interview with: Dr. Ryan Hartmaier PhD Postdoctoral Associate Magee-Womens Research Institute (MWRI) and the University of Pittsburgh Cancer Institute Medical Research: What is the background for this study? What are the main findings? Response: The inhibition of signaling through the estrogen receptor is a major target in breast cancer therapy. However, within recurrent disease others have recently identified point mutations within the estrogen receptor as a mechanism of resistance to this therapy. We undertook a comprehensive study of breast cancer progression by applying many next-generation sequencing technologies to a collection of paired primary-metastasis tissue samples from 6 patients. We placed special emphasis on the identification of structural variants (i.e. translocations, duplications, inversions, and deletions) acquired in metastatic breast cancer. In one patient with recurrent disease while on endocrine therapy, we identified a fusion gene between ESR1 (estrogen receptor alpha) and DAB2 (disabled-2). In vitro functional studies indicate that this fusion is constitutively active and hormone independent.
Author Interviews, Breast Cancer, Imperial College / 17.12.2014

Fiona Larner, PhD Postdoctoral Research Associate Department of Earth Sciences, University of Oxford, South Parks Road, Oxford, UK Department of Earth Science & Engineering, Imperial College London, Exhibition Road, South Kensington, London, UKMedicalResearch.com Interview with: Fiona Larner, PhD Postdoctoral Research Associate Department of Earth Sciences, University of Oxford, South Parks Road, Oxford, UK Department of Earth Science & Engineering, Imperial College London, Exhibition Road, South Kensington, London, UK Medical Research: What is the background for this study? What are the main findings? Response: Zinc has been identified to have a role in breast tissue and breast cancer for over a decade. Zinc has several isotopes (different versions of zinc due to varying numbers of neutrons), which require slightly different amounts of energy to go through biological processes. By measuring the changes in the zinc isotopic signature, we can probe it's behaviour to a greater resolution to that currently available in medical institutions. We looked at the isotopic signatures in different tissues of healthy patients and those with breast cancer in order to understand the mechanisms involved in more detail and in search for a biomarker that uses these signatures to diagnose breast cancer. We found that preferentially retains the lighter isotopes of zinc to a greater extent than healthy breast tissue. This means that the partnering heavy isotopes must be ejected from the cell, and may provide a biomarker for cancer in the future.
Author Interviews, Breast Cancer, NEJM / 16.12.2014

Prudence A. Francis, M.D Associate Professor , Peter MacCallum Cancer Centre Melbourne, AustraliaMedicalResearch.com Interview with: Prudence A. Francis, M.D Associate Professor, Peter MacCallum Cancer Centre Melbourne, Australia Medical Research: What is the background for this study? What are the main findings? Response: The background for this study was the observation that premenopausal women diagnosed with hormone receptor positive breast cancer under age 35, had an increased risk of recurrence, as compared with older premenopausal women. We postulated that this might be because this age group was less likely to enter menopause after receiving chemotherapy, and so their ovaries were continuing to produce estrogen, which might have the effect of stimulating any remaining cancer cells. The main findings were that while not all premenopausal women benefit from the addition of treatment with ovarian function suppression to , the women who underwent chemotherapy and remained premenopausal (median age 40) did have improved breast cancer outcomes. This same group of women had even further improvement in recurrence rates if the ovarian suppression was combined with an aromatase inhibitor exemestane, as compared with tamoxifen. The effects of including ovarian suppression were particularly striking in women under 35 years of age. Those premenopausal women who did not receive chemotherapy (median age 46) after discussion with their doctor, did well with tamoxifen alone and do not appear to benefit from ovarian suppression currently.
Author Interviews, Breast Cancer, JNCI, Mayo Clinic / 14.12.2014

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo ClinicMedicalResearch.com 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 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.
Author Interviews, Breast Cancer, Yale / 12.12.2014

Dr. James Yu Yale School of Medicine Cancer Outcomes, Public Policy, and Effectiveness Research Center Yale School of Medicine Department of Therapeutic Radiology New Haven, Connecticut MedicalResearch.com Interview with: Dr. James Yu Yale School of Medicine Cancer Outcomes, Public Policy, and Effectiveness Research Center Yale School of Medicine Department of Therapeutic Radiology New Haven, Connecticut Medical Research: What is the background for this study? What are the main findings? Response: Hypo fractionated radiation has been shown to be safe and effective, and more convenient for women with early stage breast cancer after lumpectomy.  It also has been identified by ASTRO as a practice that physicians can adopt to reduce healthcare expenses for patients and for society.  We looked at the National Cancer Database, a database created by the American College of Surgeons for trends in the use of hypo fractionated radiation for breast cancer through 2011.  We found that the use of hypofractionated radiation had increased to 22.8% in 2011.  I found this remarkable as it predated the ASTRO choosing widely guidelines, and indicated to me that physicians were already thinking of ways of making treatment more convenient and affordable for patients and insurers.
Author Interviews, Breast Cancer, Cancer, Duke / 12.12.2014

Rachel Blitzblau, M.D., Ph.D. Butler Harris Assistant Professor Department of Radiation Oncology Duke University Medical Center Durham, NC 27710MedicalResearch.com Interview with: Rachel Blitzblau, M.D., Ph.D. Butler Harris Assistant Professor Department of Radiation Oncology Duke University Medical Center Durham, NC 27710

Medical Research: What is the background for this study? What are the main findings? Dr. Blitzblau: Radiation reduces the risk of loco-regional recurrence. Data from the CALGB 9343 study suggests that the local benefit from adjuvant radiation is less in older women with small, . The potential acute and late toxicities of radiotherapy, patient inconvenience and healthcare costs must be considered given the small clinical benefit associated with adjuvant radiotherapy in this patient group. We looked at rates of radiotherapy in women fitting the entry criteria of this trial before and after publication of 5 year results of the CALGB trial. We found an approximately 5% decrease in use of radiotherapy overall, and noted that there seemed to be a small but significant shift in the type of radiotherapy used for these patients. Less patients received standard whole breast radiotherapy, and more received a short course of treatment to just the tumor bed plus margin called accelerated partial breast irradiation. We concluded that the publication of the trial therefore had only a very small impact on practice patterns.
Breast Cancer / 11.12.2014

Tina J. Hieken, M.D.MedicalResearch.com Interview with: Tina J Hieken, MD Department of Surgery Associate Professor of Surgery Mayo Clinic College of Medicine Rochester, MN 55905 MedicalResearch.com: What is the background for this study? Dr. Hieken: Many newly diagnosed breast cancer patients undergo breast MRI; Breast MRI includes a component of axillary imaging. However, there is limited data on MRI staging of axilla.
Annals Internal Medicine, Author Interviews, Breast Cancer, Radiology / 09.12.2014

Brian L. Sprague, PhD Office of Health Promotion Research, University of Vermont, Burlington, VT MedicalResearch.com Interview with:  Brian L. Sprague, PhD Office of Health Promotion Research, University of Vermont, Burlington, VT MedicalResearch: What is the background for this study? Dr. Sprague: Mammographic breast density refers to the appearance of breast tissue on a mammogram.  High breast density means that there is a greater amount of glandular tissue and connective tissue, which appears white on a mammogram.  It is more difficult to detect breast cancer on a mammogram when there is greater breast density.  It has also been shown that women with dense breasts are at a higher risk of developing breast cancer.  Because of these two factors, women with dense breasts have a greater chance of developing breast cancer after a normal screening mammogram than women whose breasts are not dense.  Many states have now passed laws that require mammography facilities to inform women with dense breasts so that they are aware of this.  Similar legislation is now under consideration at the national level.  More than 40% of women undergoing mammography screening have dense breasts. Researchers are trying to determine whether supplemental breast cancer screening with other tools would improve outcomes for women with dense breasts.  One possible approach is to use ultrasound imaging to screen for breast cancer in women with dense breasts after they have had a normal mammogram.  We wanted to estimate the benefits, harms, and cost-effectiveness of this approach compared to mammography screening only.  No randomized trials or observational studies have assessed long term outcomes after ultrasound screening for women with dense breasts, but we have short term data on how often cancer is diagnosed by ultrasound screening and how often false positive exams occur.  We used computer simulation modeling to estimate long term outcomes by combining the currently available data on mammography and ultrasound screening with the best available data on breast cancer risk and survival.
Author Interviews, Cancer Research, University of Michigan / 04.12.2014

MedicalResearch.com Interview with: Silvana Papagerakis M.S., M.D., Ph.D. Research Assistant Professor, Department of Otolaryngology-Head and Neck SurgeryDirector, Oral, Head and Neck Cancer Invasion and Metastasis Laboratory Ann Arbor MI Silvana Papagerakis M.S., M.D., Ph.D. Research Assistant Professor, Department of Otolaryngology-Head and Neck Surgery Director, Oral, Head and Neck Cancer Invasion and Metastasis Laboratory, Ann Arbor MI MedicalResearch: What is the background for this study? What are the main findings? Dr. Papagerakis: We had suspicions that these medications somehow had a favorable impact on patient outcomes. This led us to review our large cohort of patients and screen them for common medications, focusing on antacids. In fact, our study did show that people taking antacids are doing better. What this study makes clear is that these medications may be more beneficial to the patients than just controlling side effects of chemotherapy or radiation treatment for head and neck cancer.
Breast Cancer, UCSF / 04.12.2014

Elissa R. Price, MD Assistant Professor of Clinical Radiology Director of Clinical Operations, Breast Imaging Breast Imaging Fellowship Program Director Department of Radiology and Biomedical Imaging University of California, San Francisco San Francisco, CA 94115MedicalResearch.com Interview with: Elissa R. Price, MD Assistant Professor of Clinical Radiology Director of Clinical Operations, Breast Imaging Breast Imaging Fellowship Program Director Department of Radiology and Biomedical Imaging University of California, San Francisco San Francisco, CA  94115 MedicalResearch: What is the background for this study? What are the main findings? Dr. Price: Screening mammography recommendations for the 40 - 49 age group is very controversial. 2009 USPTF guidelines emphasized taking patient context into account when making decisions for these young women. Recent publications have suggested risk-based screening strategies.  Family history and breast density are important are easily accessible risk factors. Had we been using this risk-based approach to screening mammography at our institution, we would have missed more than 3Ž4 of the screen detected breast cancers in the 40-49 age group, thereby foregoing most of the survival benefit from screening mammography.
Author Interviews, Lung Cancer, PLoS / 03.12.2014

dr_Martin_C_TammemägiMedicalResearch.com Interview with: Dr. Martin C. Tammemägi Professor (Epidemiology), Brock University Department of Health Sciences St. Catharines, Ontario, Canada L2S 3A1 Medical Research: What is the background for this study? What are the main findings? Dr. Tammemägi: Lung cancer is the leading cause of cancer death in North America and the world. Lung cancer survival following diagnosis is generally poor, in the range of 10% to 15%, and has improved little over the last four decades. The biggest recent breakthrough for reducing lung cancer mortality came with the findings of the National Lung Screening Trial (NLST), a large, well-conducted randomized screening trial, which demonstrated that low dose computed tomography (LDCT) screening versus chest X-ray (CXR) screening can reduce lung cancer mortality by 20%. Currently, most guidelines for selecting screenees for lung screening use the NLST enrolment criteria of 30 or more pack-years smoked, former smokers must have quit smoking within 15 years and ages between 55 and 74, or use a variant of the NLST criteria. The US Preventive Services Task Force (USPSTF) essentially recommends using the NLST criteria but extended the inclusion age to 80 years. The current study applied the PLCOm2012 lung cancer risk prediction model1 to NLST data and identified that the risk above which lung cancer mortality is consistently lower in the LDCT arm compared to the CXR arm, is ≥1.51% 6-year risk (65th percentile). The USPSTF and the PLCOm2012 risk ≥0.0151 criteria were then applied to the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) intervention arm smokers (the PLCOm2012 was developed in PLCO controls) to determine who would be selected for lung cancer screening. Compared to USPSTF criteria, the PLCOm2012 risk ≥0.0151 threshold selected 8.8% fewer individuals, but identified 12.4% more lung cancers (sensitivity 80.1% vs. 71.2%), and had fewer false positives (specificity 66.2% vs. 62.7%). 26% of smokers who were USPSTF criteria positive had risks below the PLCOm2012 risk ≥0.0151 threshold. Of PLCO former smokers who quit more than 15 years ago, 8.5% had PLCOm2012 risk ≥0.0151, suggesting that they might benefit from screening (2.9% of them developed lung cancer in 6 year). None of 65,711 never-smokers in the PLCO had PLCOm2012 risk ≥0.0151, indicating that never-smokers should not be screened. Individuals age ≥65–80 years had significantly higher risks and more lung cancers than those 55-64 years.
Author Interviews, Cancer Research / 02.12.2014

Dr. Pan Pantziarka Anticancer Fund, Brussels Belgium The George Pantziarka TP53 Trust, London, UKMedicalResearch.com Interview with: Dr. Pan Pantziarka Anticancer Fund, Brussels Belgium The George Pantziarka TP53 Trust, London, UK MedicalResearch: What is the background for this study? Dr. Pantziarka: The background of this study is that it is part of a series of investigations by the Repurposing Drugs in Oncology (ReDO) project into well-known non-cancer drugs which have evidence of activity that may be useful in cancer therapies. These drugs include mebendazole, itraconazole, diclofenac, nitroglycerin and cimetidine.
Author Interviews, Cancer Research / 30.11.2014

Charles Brenner, PhD Roy J. Carver Chair & Head of Biochemistry Departments of Biochemistry & Internal Medicine Carver College of Medicine University of Iowa Iowa City, IA 52242MedicalResearch.com Interview with: Charles Brenner, PhD Roy J. Carver Chair & Head of Biochemistry Departments of Biochemistry & Internal Medicine Carver College of Medicine University of Iowa Iowa City, IA  52242 Medical Research: What is the background for this study? What are the main findings? Dr. Brenner: KRAS mutations are extremely common in human malignancies. The KRAS gene is an oncogene that drives cell growth pathways and that leads to silencing and inactivation of tumor suppressor genes. It was known that KRAS mutant cancer cells silence tumor suppressor genes but the precise mechanism for gene silencing was not known. In this study, we discovered that KRAS mutations turn off the TET1 gene. TET1 functions as an "eraser" of gene silencing marks. When KRAS mutations occur, the TET1 eraser isn't expressed any longer, and a series of tumor suppressor genes become silenced. This is an essential part of the aggressiveness of KRAS-dependent cancers and is controlled by the ERK pathway that is turned on by KRAS. In short, KRAS turns on ERK, which turns off TET1. When TET1 is off, a set of tumor suppressor genes are also turned off, which drives cancer formation.
Author Interviews, Prostate, Prostate Cancer, Testosterone / 29.11.2014

MedicalResearch.com Interview with: Prof. h.c.* Dr. Farid Saad on behalf of Dr. Haider and co-authors Global Medical Affairs, Andrology c/o Bayer Pharma AG, D-13342 Berlin *Gulf Medical University, Ajman, UAE Medical Research: What is the background for this study? Response: In early 1940s Dr. Charles Huggins demonstrated that in few men with metastatic prostate cancer, castration reduced tumor growth and androgen administration promoted tumor growth. This observation became the corner stone of androgen deprivation therapy (ADT) in men with prostate cancer for the past 7 decades without any clinical evidence to the contrary. Indeed, normal prostate growth depends on androgens and therefore testosterone and its metabolite DHT are responsible for the biochemical signaling in the prostate cells through interaction with the androgen receptor. Since tumor cells have been transformed from normal epithelial cells, it is no surprise that they retained the expression of the androgen receptor and continue to depend on their growth on the androgen signal. For the past 7 decades, physicians thought that testosterone is a carcinogen for the prostate, despite lack of any biochemical or clinical data. This long period of training physicians on this unproven concept, has precipitated in the minds of many clinicians that testosterone (T) causes prostate cancer. Based on a plethora of clinical data, there is no evidence to support such myth. In fact, many recent studies have debunked this hypothesis based on longitudinal and prospective studies. A newly advanced hypothesis was formulated suggesting that “T therapy does not pose a greater risk for development of PCa.” However this hypothesis is met with considerable skepticism. Interestingly, however, no new compelling evidence is available to discredit or dismiss this newly advanced hypothesis.
Author Interviews, Breast Cancer / 28.11.2014

Ben Ho Park, M.D., Ph.D. Associate Professor of Oncology, Breast Cancer Program Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD 21287MedicalResearch.com Interview with: Ben Ho Park, M.D., Ph.D. Associate Professor of Oncology, Breast Cancer Program Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD  21287 Medical Research: What is the background for this study? What are the main findings? ​Dr. Park: To discover genetic mediators of tamoxifen resistance in breast cancers, we used genetic screening of breast cancer cell line models and patient data to ​identify a new gene that can mediate drug resistance. We found that amplification and overexpression of this gene in estrogen receptor positive breast cancers results in resistance and is associated with worse outcomes in patients whose tumors demonstrate amplification/overexpression of this gene.
Author Interviews, Cancer Research, Lancet / 28.11.2014

Dr Claudia Allemani PhD FHEA MFPH Senior Lecturer in Cancer Epidemiology Cancer Research UK Cancer Survival Group Department of Non-Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine, London UKMedicalResearch.com Interview with: Dr Claudia Allemani PhD FHEA MFPH Senior Lecturer in Cancer Epidemiology Cancer Research UK Cancer Survival Group Department of Non-Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine, London UK Medical Research: What is the background for this study? Dr. Allemani:  Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. The first CONCORD study was published in 2008.1 It brought together data from 101 cancer registries in 31 countries, and included 1.9 million patients diagnosed during 1990-94 with a cancer of the colon, rectum, breast or prostate and followed up to the end of 1999. It revealed very wide international differences in five-year survival, and it confirmed the well-known racial discrepancy in cancer survival in the USA. CONCORD-2 is the most comprehensive international comparison of trends in population-based cancer patient survival to date. It extends the first study in three ways:
  • it covers 10 common cancers: collectively, these account for almost two-thirds (63%) of all cancer patients diagnosed each year in both developed and developing countries
  • it includes data on more than 25 million cancer patients, provided by 279 cancer registries in 67 countries, in 40 of which the data provide complete (100%) coverage of the national population
  • it examines trends in cancer survival for patients diagnosed over the 15-year period 1995-2009
Author Interviews, Breast Cancer / 25.11.2014

MedicalResearch.com Interview with Dr. Jonathan Myles Centre for Cancer Prevention, Queen Mary, University of London Wolfson Institute of Preventive Medicine, Charterhouse Square, London Medical Research: What is the background for this study? What are the main findings? Dr. Myles: Breast cancer screening uptake is low in areas of high social deprivation and large populations of some ethnic groups.  The main  finding of this study is that an intervention in the form of contacting women by telephone a few days before the date of their screen, reminding them of their appointment and answering any queries they may have, significantly increases uptake.
Author Interviews, Cancer Research, JAMA, Surgical Research, Toxin Research / 24.11.2014

MedicalResearch.com Interview with: Naveed Nosrati MD Indiana University School of Medicine Staff Surgeon, Roudebush VAMC Medical Research: What is the background for this study? Dr. Nosrati: We originally began this study as a broader project investigating the effect of trauma induced by biopsies on the spontaneous clearance of a non-melanoma skin cancer. As part of that, we created a large database with many patient variables. Since we undertook this project at our local VA hospital, one of the variables available to us was Agent Orange exposure. Shortly after completing the study, Clemens et al published their study linking Agent Orange exposure to higher rates of invasive non-melanoma skin cancer. Their study was a pilot study of only 100 patients. As we had well over 1,000 patients, we decided to pursue a side project of how Agent Orange specifically affects our results. Our study was operating under the hypothesis that trauma induced by biopsies led to an inflammatory response that often led to the immunologic clearance of the remaining skin cancer. We actually coined the term “SCORCH” lesion, or spontaneous clearance of residual carcinoma histologically, for this phenomenon. With that mind, we would expect patients exposed to Agent Orange to theoretically have a more invasive form of malignancy and thus have lower rates of spontaneous clearance.
Author Interviews, Melanoma / 23.11.2014

Gery P. Guy Jr., PhD, MPH, Health economist CDC: Division of Cancer Prevention and Control’s Epidemiology and Applied Research Branch.Medical Research.com Interview with: Gery P. Guy Jr., PhD, MPH, Health economist CDC: Division of Cancer Prevention and Control’s Epidemiology and Applied Research Branch. Medical Research: What is the background for this study? Dr. Guy: Skin cancer is the most commonly diagnosed cancer in the United States and is a growing public health problem. Melanoma, the deadliest form of skin cancer, is responsible for more than 12,000 deaths each year and is diagnosed in over 70,000 people per year. The number of skin cancer cases continues to increase every year, however little is known about the economic burden of treatment. The purpose of our study was to examine trends in the number of people treated for skin cancer and the cost of treatment.
Author Interviews, Breast Cancer, JAMA, Surgical Research, Vanderbilt / 20.11.2014

MedicalResearch.com Interview with: Dr. Kristy Lynn Kummerow MD Division of Surgical Oncology and Endocrine Surgery Vanderbilt University Medical Center Tennessee Valley Healthcare System, Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Center Nashville, Tenn Medical Research: What is the background for this study? What are the main findings? Dr. Kummerow: This study looked at how we are currently treating early stage breast cancer in the US – early stage breast cancer includes small cancers with limited or no lymph node involvement and no spread to other body site – it was prompted by something we observed an our own cancer center, which is that more and more women seem to be undergoing more extensive operations than are necessary to treat their cancer.  It is helpful to understand the historical context of how we treat early breast cancer.  Prior to the 1980s, the standard of care for any breast cancer was a very extensive procedure, which involved removal of the entire breast, as well as underlying and overlying tissues and multiple levels of lymph nodes drained by that area.  Informative clinical trials were completed in the 1980s demonstrated that these extensive procedures were unnecessary, and that equivalent survival could be achieved with a much more minimal operation, by removing only the tumor, with a margin of normal breast tissue around it, and performing radiation therapy to the area; this technique is now known as breast conservation surgery, also known as lumpectomy with radiation.  In the 1990s, breast conservation was established by the national institutes of health and was embraced as a standard of care for early stage breast cancer; performance of breast conservation surgery also became a quality metric – accredited breast centers in the US are expected to perform breast conservation surgery in the majority of women who they treat for breast cancer.  However, what our research team observed at our institution didn’t fit – over time it appears more aggressive surgical approaches are being used for more women.  This has been found in other institutions as well, and is supported by smaller national studies.  We wanted to understand how surgical management of early breast cancer is changing over time at a national level using the largest data set of cancer patients in the United States.
Author Interviews, Biomarkers, Lung Cancer / 20.11.2014

Marie-Christine Aubry, M.D. Professor of Laboratory Medicine and Pathology Consultant, Department of Laboratory Medicine and Pathology, Mayo Clinic in Rochester, Minn.MedicalResearch.com Interview with: Marie-Christine Aubry, M.D. Professor of Laboratory Medicine and Pathology Consultant, Department of Laboratory Medicine and Pathology, Mayo Clinic in Rochester, Minn.   Medical Research: What is the background for this study? What are the main findings? Dr. Aubry: Up to 20% of patients will present with multifocal lung cancer or will develop a second lung cancer.  The main clinical issue is distinguishing between independent primaries from true intrapulmonary metastases since this distinction will drive the therapy of the patient.  Currently no ancillary studies allows for this distinction and the distinction is provider specific based on a combination of clinical, radiologic and pathologic assumptions. Based on our prior research using a method called mate pair sequencing , we observed that the probability of detecting identical chromosomal breakpoints in two unrelated tumors, from 2 different patients was basically zero. Similarly, when assessing different components within a single tumor, we always found identical chromosomal breakpoints between these components.  We thus hypothesized that if two tumors within a patient were related, i.e. true metastasis, we should always find a number of identical chromosomal breakpoints between the tumors. And in contrast, if 2 tumors were truly independent primaries, we should not observe any chromosomal breakpoints in common. We first studied a control group of patients that had 1- a primary lung cancer with a known distant metastasis (usually brain metastasis), 2- two lung cancers of different histologic subtype, adenocarcinoma and squamous cell carcinoma which are accepted as true independent primaries and 3- 1 tumor with different portions of the tumor being analyzed individually and compared as true relatedness. There were thus a total of 11 pairs of tumors with predetermined status of independent primaries versus relatedness (ie metastasis or same tumor).  The mate pair generated data showed a perfect concordance with this status.  We then studied 11 pairs of lung tumors of similar histology (2 adenocarcinomas or 2 squamous cell carcinomas).  The current gold standard for the distinction between independent primaries and intrapulmonary metastasis relies on a pathologist’s comparative morphologic assessment. In order to strengthen this gold standard, 2 pulmonary pathologists independently made this assessment. Interestingly, the pathologists agreed on the status of independent primaries and intrapulmonary metastasis in 9 (of 11) cases demonstrating the shortcomings of this gold standard.  Furthermore, there were discordance between the pathologists’ prediction and the clinicians’ assessment in 3 of the 11 patients and the clinician could not come to a final assessment in 1 patient.  The MP data was concordant with the pathology assessment in 8 of these 9 cases, and supported the pathologists’ prediction in 2 (of the 3) discordance with the clinical assumptions.
Breast Cancer, Exercise - Fitness / 20.11.2014

MedicalResearch.com: Interview Invitation Dr. Wenji Guo University of Oxford Medical Research: What is the background for this study? Response: Previous studies report increased risk for breast cancer in postmenopausal women who have a higher Body Mass Index (BMI) – a measure of body fat based on height and weight. However, BMI is unable to distinguish between excess weight due to fat rather than muscle. More direct measures of fatness, such as body fat percentage, may be better indicators of disease risk. And although probable evidence for the relationship between physical activity and breast cancer now exists, questions still remain over the role of vigorous compared to lower intensity physical activity.