Author Interviews, Breast Cancer, JAMA, Leukemia / 03.06.2015

Efrat Amitay, PhD, MPH School of Public Health University of Haifa Mount Carmel, Haifa, IsraelMedicalResearch.com Interview with: Efrat Amitay, PhD, MPH School of Public Health University of Haifa Mount Carmel, Haifa, Israel Medical Research: What is the background for this study? Dr. Amitay: Although childhood cancer is still rare, we are seeing an increase of around 0.9% annually in the incidence rate in the western world. In spite of advancements in treatment technologies, childhood cancer is a leading cause of death among children and adolescents in the western world – accounting for about 12.3% of all deaths among children age 1-14 years in the US. Childhood cancer is also emerging as a major cause of death in other parts of the world where death rates from communicable diseases are declining. Leukemia is the most common type of childhood cancer and accounts for about 30% of all childhood and adolescent cancers. Medical Research: What are the main findings? Dr. Amitay: The meta-analysis of all 18 studies indicated that compared with no or shorter duration of breastfeeding, breastfeeding for 6 months or longer was associated with a 19% lower risk for childhood leukemia (OR=0.81, 95% CI, 0.73-0.89). A separate analysis of 15 of those studies indicated that ever being breastfed compared with never being breastfed was associated with an 11% lower risk for childhood leukemia (OR=0.89, 95% CI, 0.84-0.94). All meta-analyses of other sub groups of studies have shown similar associations, indicating that 14%-19% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. (more…)
Author Interviews, Biomarkers, Breast Cancer / 03.06.2015

Daniel F. Hayes, M.D. Stuart B. Padnos Professor of Breast Cancer Research University of Michigan Comprehensive Cancer Center Ann Arbor MIMedicalResearch.com Interview with: Daniel F. Hayes, M.D. Stuart B. Padnos Professor of Breast Cancer Research University of Michigan Comprehensive Cancer Center Ann Arbor MI Medical Research: What is the background for this study? What are the main findings? Dr. Hayes: We have developed a circulating tumor cell endocrine therapy index that we hypothesize will identify patients with estrogen receptor positive metastatic breast cancer but who will not benefit from endocrine (anti-estrogen) therapy. We can now semi-quantifiably measure er as well as bcl2, her2, and ki67 in a highly accurate and reproducible fashion.  We are now conducting a multi-institutional prospective trial in North America (the Circulating Tumor Cell-Endocrine Therapy COMETI study) to determine if our hypothesis is correct. (more…)
Author Interviews, Immunotherapy, Melanoma / 02.06.2015

Prof. Ze'ev Ronai Ph.D Scientific Director Sanford-Burnham's La JollaMedicalResearch.com Interview with: Prof. Ze'ev Ronai Ph.D Scientific Director Sanford-Burnham's La Jolla Medical Research: What is the background for this study? What are the main findings? Prof. Ronai: There is an urgent need to find new approaches to treat melanoma in patients that are resistant to current therapeutic regimes—and this represents a significant percent of melanoma patients.  We used  samples from patients with drug resistant tumors  to study the molecular basis of resistance and screened for genes involved in the process. We have identified a new player in melanoma resistance to therapy—a molecular target, which provides the basis for clinical trials with drugs currently available to these targets. We found that JAK1 kinase is one target that  is upregulated in the resistant tumors. Inhibiting JAK1 kinase can effectively overcome such resistance.  (more…)
ASCO, Author Interviews, Journal Clinical Oncology, Melanoma / 02.06.2015

Howard L. Kaufman, MD, FACS Rutgers Cancer Institute of New Jersey New Brunswick, NJMedicalResearch.com Interview with: Howard L. Kaufman, MD, FACS Rutgers Cancer Institute of New Jersey New Brunswick, NJ Medical Research: What is the background for this study? What are the main findings? Response: The study clearly demonstrated that advanced melanoma patients achieved a significant improvement in both response rate and durable response rate with Talimogene laherparepvec, or T-VEC. T-VEC is the first oncolytic virus to show a clinical benefit in a randomized phase 3 clinical trial for the treatment of cancer. Patients who received T-VEC also had an improved progress-free and overall survival with nearly 11% obtaining a complete response. T-VEC is an oncolytic virus that mediates anti-tumor activity by directly killing injected tumor cells and by initiating a systemic immune response. Treatment was also associated with few side effects, which were mostly low grade fever, fatigue, chills, nausea and pain at the injection site. (more…)
Author Interviews, Nutrition, Prostate Cancer / 01.06.2015

Meng Yang, PhD MPH Research Fellow Harvard T. H. Chan School of Public HealthMedicalResearch.com Interview with: Meng Yang, PhD MPH Research Fellow Harvard T. H. Chan School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Yang: There are nearly 3 million American men living with prostate cancer. However, there is very little information for patients and clinicians about how to manage patients’ lifestyles, like diet, after prostate cancer diagnosis to decrease the risk of death due to this disease and improve their survivorship. The most important finding is that men initially diagnosed with prostate cancer without metastases whose diet was more “Westernized”, i.e. higher processed meats, refined grains, potatoes and high-fat dairy, had a significantly higher prostate cancer-related death and all cause mortality. Men whose diet was more “prudent”, i.e. higher intake of vegetables, fruits, fish, whole grains and healthy oils had a lower risk of death. (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, NEJM, Surgical Research, Yale / 31.05.2015

Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACSAssociate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT 06510MedicalResearch.com Interview with: Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven, Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT, Medical Research: What is the background for this study? What are the main findings? Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer -- the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease.  The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind.  No one likes to go back to the operating room -- so we asked the question, "How can we do better?".  Surgeons have debated various means of obtaining clear margins.  Some have advocated taking routine cavity shave margins -- a little bit more tissue all the way around the cavity after the tumor is removed at the first operation.  Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) -- i.e., selective margins.  We conducted a randomized controlled trial to answer this question.  We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit.  After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would ("NO SHAVE"), or take a bit more tissue all the way around the cavity ("SHAVE"). Patients in both groups were evenly matched in terms of baseline characteristics.  The key finding was that patients who were randomized to the "SHAVE" group half as likely to have positive final margins and require a re-operation than patients in the "NO SHAVE" group.  On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results.  While the volume of tissue excised in the "SHAVE" group was higher than in the "NO SHAVE" group, the distribution of patient-perceived cosmetic outcomes were identical in both groups.  Complication rate was also no different between the two groups.  We will be following patients for five years for long-term cosmetic and recurrence outcomes. (more…)
ASCO, Author Interviews, Cancer Research / 31.05.2015

Tanguy Seiwert, MD Assistant Professor, Dept. of Medicine Associate Director, Head and Neck Cancer Program Section of Hematology/Oncology Fellow, Institute for Genomics and Systems Biology Speciality Chief Editor, Frontiers in Head and Neck Cancer University of Chicago Chicago, IL 60637MedicalResearch.com Interview with: Tanguy Seiwert, MD Assistant Professor, Dept. of Medicine Associate Director, Head and Neck Cancer Program Section of Hematology/Oncology Fellow, Institute for Genomics and Systems Biology Speciality Chief Editor Frontiers in Head and Neck Cancer University of Chicago Chicago, IL 60637 Medical Research: What is the background for this study? Dr. Seiwert: Recurrent/metastatic Head and Neck Squamous Cell Cancer (HNSCC) remains poorly treatable with a median OS of 10-13 months There is evidence of a  prominent immune escape observed in squamous cell carcinoma of the head and neck (SCCHN) suggesting that anti-PD1 agents (similar to e.g. melanoma) may be active. Medical Research: What are the main findings? Dr. Seiwert:
  • One in four patients with Head/Neck cancer treated with pembrolizumab showed marked tumor shrinkage (so called – partial/complete responses), and 57% of patients experienced any decrease in the size of their tumors.
  • Pembrolizumab is broadly active in both HPV(-) and HPV(+) types of squamous cell carcinoma of the head and neck.
  • Pemborliuzmab treatment is active in heavily pretreated squamous cell carcinoma of the head and neck patients.
  • Responses seem to be durable è 86% of responding patients remain in response.
Treatment overall was well tolerated with less than 10% of patients experiencing severe side effects (≥Grade 3). (more…)
Author Interviews, Breast Cancer, General Medicine / 31.05.2015

MedicalResearch.com Interview with: Bruno M. Heleno MD The Research Unit for General Practice and Section of General Practice Department of Public Health University of Copenhagen Medical Research: What is the background for this study? What are the main findings? Dr. Heleno: False positive mammography causes psychological distress. Several observational studies have shown this, and their results have been summarized in systematic reviews. However, it was unclear whether women requiring invasive tests (needle or surgical biopsy) were more distressed than women only requiring non-invasive procedures (clinical examination or imaging). Contrary to previous research, we found that these two groups of women were equally distressed during the 36 months of follow-up in our cohort. The best estimate for the difference for 12 related measures of distress was always close to zero. (more…)
ASCO, Author Interviews, Journal Clinical Oncology, Mayo Clinic / 31.05.2015

Ruben A. Mesa, MD, FACP Consultant Hematologist Chair, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center Scottsdale, AZMedicalResearch.com Interview with: Ruben A. Mesa, MD, FACP Consultant Hematologist Chair, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center Scottsdale, AZ Medical Research: What is the background for this study? What are the main findings? Dr. Mesa: Myelofibrosis is a rare and chronic blood cancer associated with significantly reduced quality of life and shortened survival. In patients with this disease, spleen enlargement (splenomegaly) is a very common and debilitating symptom – and as the disease progresses, the body slows production of important blood cells. The results presented at ASCO were from the PERSIST-1 study, which is a Phase 3 registration-directed trial designed to compare pacritinib — an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3 – to best available therapy (exclusive of a JAK inhibitor) in patients with myelofibrosis — regardless of their platelet counts.  Data from this study showed that compared to best available therapy, pacritinib resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms, regardless of platelet levels at the time of enrollment. (more…)
Author Interviews, Baylor College of Medicine Houston, Cancer Research, Colon Cancer, Gender Differences / 29.05.2015

Dr. Aaron P. Thrift PhD Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle, WA.MedicalResearch.com Interview with: Aaron P. Thrift, Ph.D. Assistant Professor, Department of Medicine Dan L. Duncan Cancer Center Baylor College of Medicine Houston, TX 77030-3498 Medical Research: What is the background for this study? What are the main findings? Dr. Thrift: Greater attained adult height is associated with increased risk of all cancers combined; however, the association may differ by cancer site and between women and men. For colorectal cancer, epidemiological studies suggest that the association with height may be stronger for women than for men. We used data from over 10,000 patients with colorectal cancer and over 10,000 population-based controls and conducted multiple analyses, including using Mendelian randomization (which incorporates genomic data with traditional approaches) to overcome potential issues of confounding and bias in observational studies, to further examine the association between height and risk of colorectal cancer. Overall, we found that taller height was associated with increased risk of colorectal cancer (8% increased risk per 10cm increase in height). When we examined women and men separately, our results strongly suggest that height is causally associated with colorectal cancer risk for women, whereas there was weaker evidence for a causal association between height and colorectal cancer risk for men. (more…)
Author Interviews, Biomarkers, Nature, Prostate Cancer, Technology / 27.05.2015

Gabriel Popescu PhD Associate Professor Department of Electrical and Computer Engineering & Bioengineering University of Illinois at Urbana-Champaign Beckman Institute for Advanced Science and Technology Urbana, IL 61801MedicalResearch.com Interview with: Gabriel Popescu PhD Associate Professor and Shamira Sridharan, Ph.D. candidate Quantitative Light Imaging Laboratory, Department of Bioengineering, Beckman Institute for Advanced Science and Technology University of Illinois at Urbana Champaign Urbana, IL Medical Research: What is the background for this study? What are the main findings? Dr. Popescu: We developed a new optical tool that can identify patients at high risk for recurrence of prostate cancer after undergoing radical prostatectomy as treatment.  Early identification of risk for recurrence can allow early treatment of disease. Our main finding was that among individuals with worse disease outcomes, the tissue is more disorganized.  This manifests as a decrease in anisotropy, or light scattering angle, which reports on nano-scale differences in tissue architecture. (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 77030MedicalResearch.com 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, Cancer Research, JAMA, Toxin Research / 26.05.2015

MedicalResearch.com Interview with: Catterina Ferreccio, MD, MPH School of Medicine Pontificia Universidad Católica de Chile Santiago, Chile Medical Research: What is the background for this study? What are the main findings? Dr. Ferreccio: In Chile, gallbladder cancer (GBC) is the 2nd highest cause of cancer death in women.  Other than gallstones no other causal factors have been identified. We conducted a pilot case-control study of gallbladder cancer to evaluate its association with aflatoxin B1 (AFB1) exposure. Aflatoxins are toxics products of the fungis Aspergillus flavus and Aspergillus parasiticus and are contaminants of food; AFB1 is carcinogenic. Usually they are found in areas closer to the Equator than Chile. Main findings were the high proportion (35%) of study subjects carrying aflatoxins adducts and the particularly high exposure among the Gallbladder cancer (GBC) cases (64%) compared with gallstones controls (18%) or with population controls (23%). Difference of gallbladder cancer vs controls were statistically significant and suggests aflatoxins may be a significant risk factor for gallbladder cancer; hypothesis never tested before. (more…)
Author Interviews, Breast Cancer / 26.05.2015

Professor Ramsey Cutress Associate Professor in Breast Surgery University of SouthamptonMedicalResearch.com Interview with: Professor Ramsey Cutress Associate Professor in Breast Surgery University of Southampton Medical Research: What is the background for this study? What are the main findings? Response: The main finding is that in young women with breast cancer, a breast cancer family history of breast cancer did not affect recurrence rates. This work forms part of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study, which included 2850 women under age 41 years who were diagnosed with breast cancer and treated in the UK. The study, led by principal investigator Professor Diana Eccles, recorded patients’ personal characteristics, tumour characteristics, treatment, and family history of breast/ovarian cancer over a 15-year period. (more…)
Author Interviews, Lancet, Ovarian Cancer, Surgical Research / 22.05.2015

MedicalResearch.com Interview with: Mr Matthew Nankivell MRC Clinical Trials Unit at University College London Institute of Clinical Trials and Methodology Aviation House, London UK Medical Research: What is the background for this study? What are the main findings? Response: Ovarian cancer is diagnosed in over 7000 women each year in the UK. Over 75% of these already have advanced disease, for which the standard treatment is surgery followed by platinum based chemotherapy. The prognosis for these patients remains poor however, with less than 25% surviving for 5 years. There is consistent evidence that achieving optimal debulking (meaning less than 1cm of residual tumour after surgery) is key to increasing survival. The theory tested in Chorus is that giving the chemotherapy before surgery (neo-adjuvantly) would be as least as effective as giving it post-operatively, and may in fact increase the chance of achieving optimal debulking, and subsequently living for longer. In Chorus we randomised 552 women to receiving either the current standard of immediate surgery followed by chemotherapy, or chemotherapy followed by surgery. The trial met its primary aim of showing that neo-adjuvant chemotherapy was no worse than post-operative chemotherapy, with median survival times of 24.1 and 22.6 months respectively. The proportion of women achieving optimal debulking increased from 41% in the post-operative chemotherapy group to 73% in the neo-adjuvant chemotherapy group. Additionally we saw that fewer women experienced serious post-operative complications having had neo-adjuvant chemotherapy (14% vs 24%), and fewer women died within 28 days of surgery (<1% vs 6%). There is a planned meta-analysis, to combine the data from Chorus with those from a similar European trial, which will allow further investigations to take place, and may allow the identification of groups of women who are more likely to benefit from one or other of the approaches. (more…)
Author Interviews, Biomarkers, Colon Cancer / 22.05.2015

Dr. Jeanne Tie Medical Oncologist | Royal Melbourne and Western Hospital Research Fellow Walter and Eliza Hall Institute of Medical Research Parkville, VICMedicalResearch.com Interview with: Dr. Jeanne Tie Medical Oncologist | Royal Melbourne and Western Hospital Research Fellow Walter and Eliza Hall Institute of Medical Research Parkville, VIC Medical Research: What is the background for this study? Dr. Tie: The increasing number of active agents available to treat metastatic colorectal cancer has resulted in an ever-improving life expectancy in this group of patients. However, the ability to expose patients with metastatic colorectal cancer to all effective anti-cancer treatment, particularly 3rd line treatment and beyond, is increasingly challenging in routine practice as some patients’ condition deteriorate too rapidly and do not live long enough to enjoy the benefit of these additional therapies. This is partly due to the current imaged-based method of assessing treatment response with the Response Evaluation Criteria in Solid Tumors (RECIST), which is usually performed every 8-12 weeks during the course of treatment. This means that for non-responders to treatment, several weeks to months will elapse before a switch to alternative therapy will be made. Conceptually, if a patient’s response to treatment could be made earlier, such as with a blood test,  then an earlier switch to an alternative treatment can be made, minimizing the side-effects of the ineffective therapy and providing the opportunity for a more effective one. Currently, blood biomarkers add little to imaging-based assessment, with CEA lacking sensitivity and specificity. Colorectal cancer is characterised by several recurrently mutated genes and advances in genomics and molecular technologies have now enabled rapid detection and quantification of these cancer-specific mutations in patient’s circulation (circulating tumor DNA - ctDNA). Previous studies have demonstrated that ctDNA can be detected in a high proportion of patients with advanced cancer. In this study, we describe the potential role of ctDNA as an early predictor of treatment response in patients with treatment naïve metastatic colorectal cancer (mCRC) undergoing chemotherapy and as a marker of disease bulk that could complement RECIST measurement. (more…)
Author Interviews, Biomarkers, Breast Cancer / 19.05.2015

Lao Saal, M.D. Ph.D.MedicalResearch.com Interview with: Lao Saal, M.D. Ph.D. Head, Translational Oncogenomics Unit Assistant Professor Department of Oncology and Pathology Lund University Cancer Center Lund, Sweden Medical Research: What is the background for this study? Dr. Saal: About a quarter of women diagnosed with primary (non-metastatic) breast cancer will unfortunately progress and later be found to have metastatic spread, which can occur many years to even a decade or more after the first diagnosis. At this point, the prognosis after identification of metastatic breast cancer is very poor. Metastatic disease is typically diagnosed only after it has grown large enough to cause symptoms, be noticed on exam, or be detectable by imaging. It is thought that early detection of metastasis has the potential to lead to better outcomes because therapies could be modified when the metastasis is still very small. Moreover, a very sensitive and specific test that could identify patients who appear "cancer-free" could also be useful. Essentially all cancers have unstable genomes, where chromosomes physically break and are reassembled incorrectly and thus the normal sequence is altered. Importantly, DNA material from cancer cells can be found in the blood circulation and therefore this circulating tumor DNA has the potential to be a cancer biomarker. Medical Research: What are the main findings? Dr. Saal: Eleonor Olsson, a PhD student in my lab who defends her thesis next week, and Christof Winter, a postdoc bioinformatician in my group, were the first authors of the paper. In our study we tested whether periodic monitoring of circulating tumor DNA (ctDNA) in blood plasma samples, taken before surgery for primary breast cancer and at multiple timepoints after surgery, could identify the metastastic spread, and whether the quantity of ctDNA was associated to patient outcome. We analyzed a retrospective cohort of 20 patients, who had enrolled many years ago in a separate epidemiological study run by Helena Jernström in our department, wherein the appropriate blood plasma samples had been biobanked and tumor tissue was available and we had long-term clinical follow-up information. As far as we are aware, our study is the first to show the potential for serial ctDNA monitoring in the context of primary breast cancer. We found that our ctDNA blood tests could discriminate patients with eventual metastasis from those with long‐term disease‐free survival with 93% sensitivity and 100% specificity. Furthermore, ctDNA‐based detection of metastatic disease preceded clinical detection for 86% of patients by an average 11 months and in some cases by 3 years. In all of the patients who had long-term disease-free survival, we did not detect any ctDNA in any timepoints after surgery. Lastly, the measured quantity of ctDNA was a significant predictor of outcome: for each doubling of the ctDNA level, the odds ratio for metastasis was 2.1 and the odds ratio for death was 1.3. An interesting anecdote -- one patient we studied had bilateral breast cancer and we found that it was the right-side tumor (which actually had more favorable clinical characteristics) that gave rise to the metastasis and not the left-side tumor. (more…)
Author Interviews, Prostate Cancer / 17.05.2015

MedicalResearch.com Interview with: Michael Fenstermaker MD NYU School of Medicine | MD, MS | Class of 2015 Northwestern University | BA | Biochemistry, Psychology Medical Research: What is the background for this study? What are the main findings? Dr. Fenstermaker: The benefits of using prostate-specific antigen (PSA) testing to screen for prostate cancer are uncertain. In response to this, many medical societies have recently scaled back their recommendations for PSA screening.  One common thread among these groups is that shared decision-making should guide whether or not men get tested. Shared decision-making is a process by which physicians and patients work together to make a medical decision that aligns with the patient’s values and follows the best available medical evidence. Several studies have shown a decline in PSA testing since new guidelines have been published.  While a decrease in screening is not necessarily problematic itself, it could be an issue if this is the result of fewer physicians discussing screening with their patients. Some experts worry that disparities in screening could develop, such that only informed patients go on to speak with their physicians and receive PSA testing.  By analyzing data from a national survey, we had the chance to investigate just how much men know about the controversies leading to these guidelines changes and whether this knowledge influences PSA usage. Our findings show that the majority of U.S. males of screening age report that they were not informed of many key facts important to understanding the risks and controversies surrounding PSA testing.  Of particular concern, certain vulnerable populations, such as those without regular healthcare providers were less likely to be informed of these facts. Surprisingly, those men who had more awareness of the controversies about PSA testing were more likely to undergo testing.   (more…)
Author Interviews, Brigham & Women's - Harvard, Prostate Cancer / 17.05.2015

Jennifer R. Rider, ScD, MPH Assistant Professor of Medicine Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA 02115MedicalResearch.com Interview with: Jennifer R. Rider, ScD, MPH Assistant Professor of Medicine Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Rider: Numerous studies have investigated the potential role of sexual activity on the development of prostate cancer. However, most of these studies have been small and retrospective, making them more prone to bias. In addition, previous studies often relied on proxies of exposure for sexual activity (number of sexual partners, age at first marriage, etc.), which may not adequately measure the aspects of sexual activity that are most important for prostate health. The current study is the largest prospective study to date on ejaculation frequency and prostate cancer. It includes 18 years of follow up of almost 32,000 healthy men, 3839 of whom later were diagnosed with prostate cancer.  We asked men about their average monthly frequency of ejaculation between the ages of 20-29, 40-49, and in the year prior to the questionnaire (1991). We find that frequency of ejaculation throughout life course is inversely associated with risk of prostate cancer at all three of these time points. For instance, men who have an average monthly ejaculation frequency of 21 or more times/moth at ages 40-49 have a statistically significant 22% reduction in risk of developing prostate cancer compared to men with a frequency of 4-7 times/month, adjusting for multiple dietary and lifestyle factors, and prostate cancer screening history. (more…)
Prostate Cancer / 17.05.2015

Ryan P. Terlecki, MD, FACS Director, Men's Health Clinic Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist HealthMedicalResearch.com Interview with: Ryan P. Terlecki, MD, FACS Director, Men's Health Clinic Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist Health Medical Research: What is the background for this study? What are the main findings? Response: In recent years, the value of generalized screening for prostate cancer (PCa) in adult men has been questioned, with several national associations recommending against the practice in men without recognized risk factors. Screening, when performed, often consists of a blood test for prostate specific antigen (PSA) and a digital rectal exam (DRE). Once PSA was developed as a screening tool, we witnessed a stage migration such that observing a locally advanced cancer that would be initially found via DRE became a rarer event. In practice, we have noticed that some men will actually avoid a clinic visit because of the DRE. Additionally, the digital rectal exam has limitations and is often poorly reproducible among providers. We chose to review a large body of data to shed some light on the utility of the digital rectal exam exam. We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening trial, to determine the ability of the digital rectal exam to result in a diagnosis of clinically significant PCa in the setting of a normal PSA. We found that if PSA is normal and digital rectal exam is considered abnormal, the chance of detecting a clinically significant cancer is similar to a situation of normal DRE and normal PSA. Also, 1,372 men would need to undergo a digital rectal exam to identify a single case of clinically significant prostate cancer not detected by PSA. (more…)
Author Interviews, Cancer Research, Wistar / 14.05.2015

Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PAMedicalResearch.com Interview with: Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PA MedicalResearch: What is the background for this study? What are the main findings? Dr. Aird: Senescence is considered an important tumor suppressor mechanism. In normal cells, activation of certain oncogenes decreases the levels of dNTPs (the building blocks of DNA), leading to replication stress. We previously found that loss of the rate-limiting enzyme in dNTP synthesis, ribonucleotide reductase M2 (RRM2), is the cause of this replication stress. Restoration of RRM2 expression could rescue the loss of dNTPs and replication stress, which overcame the senescence-associated growth arrest. Indeed, RRM2 is highly expressed in many cancer types, including melanoma and ovarian cancer. Therefore, we found that increased dNTP levels can overcome senescence and potentially lead to transformation of cells and cancer. We next wanted to further our understanding of replication stress in the context of senescence. In the current study, we suppressed nucleotide metabolism by decreasing RRM2 expression as a model for replication stress and then determined what proteins are necessary for the induction of senescence. We found that loss of ATM could overcome replication stress-induced senescence. This was due to increased dNTP levels. dNTPs were increased due to a coordinated inactivation of p53 and activation of c-MYC by loss of ATM. These changes at the molecular level correlate with reprogramming of cellular metabolism by generating dNTPs. Thus, loss of ATM in the context of replication stress can change cellular metabolism to a more cancer-like phenotype. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Journal Clinical Oncology, Stanford / 13.05.2015

MedicalResearch.com Interview with: Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CAMelinda L. Telli, M.D.
Assistant Professor of Medicine
Stanford University
Division of Medical Oncology

Stanford, CA 94305-5826
Medical Research: What is the background for this study? What are the main findings? Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC). Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%). Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. (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 NetherlandsMedicalResearch.com 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, Case Western, Genetic Research / 07.05.2015

Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Khalil: This study aimed to identify other genes that work synergistically with the oncogene HER2 in HER2positive (HER+) breast cancer. The gene HER2 is amplified in those patients, which results in excess activities that promote uncontrolled cell growth. There are drugs that target HER2 and diminish its activity. However, these drugs can work initially, but patients relapse; or sometimes, the drugs don't work at all in some patients. Thus, by identifying other genes that work synergistically with the HER2 gene, we now have more genes to target by various drugs or compounds to destroy the tumor. The challenge was how to identify the key genes that work synergistically with HER2, especially in human subjects. To that end, we used clinical samples from a clinical trial of a drug that is known to inhibit HER2 activity to identify those genes. To further refine our list, we used cell culture models of the disease to also inhibit HER2. By combining those data sets, we identified 44 protein-coding genes. Next, we wanted to make sure that those genes stand a third independent filter. For that part, we interrogated those 44 genes in HER2+ tumors vs matched normal tissues from The Cancer Genome Atlas database — a collection of hundreds of tumors and normal tissues. Of the 44 genes, 35 genes passed this third filter. By examining the known functions of those genes, we can deduce that those genes work cooperatively with HER2 to promote carcinogenesis. There are currently known drugs that target some of those genes. We will use these drugs in combination with a drug that target HER2 to determine if the combination works better at destroying the tumor entirely. Lastly, we found that a special type of genes that we previously discovered, called lincRNAs, could also affect the oncogenic activity of HER2. These lincRNAs can also be targeted with HER2 to eliminate the tumor. (more…)
Author Interviews, Prostate Cancer, Radiology / 06.05.2015

Matthias Eiber, MD Department of Nuclear Medicine Munich, GermanMedicalResearch.com Interview with: Matthias Eiber, MD Department of Nuclear Medicine Munich, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Eiber: The background of the study is the investigation of a novel 68Ga-PSMA ligand using PET/CT in the workup of patients with recurrent prostate cancer after radical prostatectomy. Hereby, we found substantial higher detection rate compared to other methods. In total 222 (89.5%) patients showed pathological findings in 68Ga-PSMA-ligand PET/CT. Stratified by PSA-level the detection rates were 96.8%,93.0%,72.7% and 57.9% of ≥2,1-<2, 0.5-<1 and 0.2-<0.5ng/mL, respectively. (more…)
Author Interviews, Cancer Research, End of Life Care, Surgical Research, UC Davis / 04.05.2015

Robert J Canter MD Associate Professor of Clinical Surgery Division of Surgical Oncology University of California at DavisMedicalResearch.com Interview with: Robert J Canter MD Associate Professor of Clinical Surgery Division of Surgical Oncology University of California at Davis Medical Research: What is the background for this study? Dr. Canter: Our data suggest that surgeons are improving in their ability to select patients for surgical intervention in cancer patients near their end of life. Our research suggests that surgeons may be operating on healthier patients who are anticipated to have a better recover from a palliative operation. These are patients who can perform activities of daily living without assistance, for example. Our interest in the appropriate surgical care of people with late-stage cancer grew from observing terminally ill patients whose acute problems were addressed through surgery, and who then suffered complications resulting in lengthy stays in intensive care units, and even in death. Unfortunately, it is quite common that this group of disseminated malignancy patients end up dying in the intensive care unit instead of being managed with less invasive interventions with hopes of returning home with their families, including with hospice care. (more…)
AACR, Author Interviews, Breast Cancer, NIH, Ovarian Cancer / 03.05.2015

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers. We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population. (more…)
Author Interviews, Cancer Research, Nature, UT Southwestern / 03.05.2015

Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical CenterMedicalResearch.com Interview with: Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology, Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. Treatments for AML yield poor outcomes, especially for the typical senior patients. The medical need for new therapies for AML is underscored by the fact that no new therapies for AML have been approved in over 30 years. There are over 50 experimental agents in clinical trials for the treatment of AML today, although only a few agents have promising data to date. New molecular targets and therapeutic strategies are needed for AML treatment. In 2012, we published a paper showing that we cloned the human leukocyte immunoglobulin-like receptor B2 (LILRB2) as a receptor for several angiopoietin-like proteins (Angptls) (Zheng et al 2012 Nature 485:656-660). The LILRB family receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and are classified as inhibitory receptors because ITIM motifs can recruit phosphatases SHP-1, SHP-2, or SHIP to negatively regulate immune cell activation. Surprisingly, in that work, we showed that PirB, the mouse ortholog of LILRB2, is expressed by AML stem cells (AML-SCs) and supports AML development. Although counterintuitive, this result is consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. In the current paper, we continued the research and report that a number of receptors containing the ITIMs are crucial for the development of AML. We mainly focus on studying the function and downstream signaling of LAIR1 as a representative ITIM-containing receptor. We found that the deletion of LAIR1 does not affect normal hematopoiesis but abolishes leukemia development in several different mouse leukemia models. We also identified a mechanism by which LAIR1 supports AML development, showing that the LAIR1/SHP-1/CAMK1/CREB pathway sustains the survival and self-renewal of AML cells. Importantly, our findings are well supported by bioinformatics analysis of AML patient databases and experimental results of human leukemia cells. Since certain ITIM-containing receptors are essential for AML cells but not critical for normal hematopoiesis, and blocking their signaling can boost immunity, these ITIM-containing receptors including LAIR1 represent ideal targets for treating AML. (more…)
Author Interviews, Cancer Research, Exercise - Fitness, Lymphoma / 02.05.2015

MedicalResearch.com Interview with: Terry Boyle, PhD CIHR Fellow, MSFHR Trainee, Honorary UBC Killam Fellow Cancer Control Research, BC Cancer Agency School of Population and Public Health, The University of British Columbia Australian NHMRC Early Career Fellow The University of Western Australia Cancer Control Research, BC Cancer Agency Vancouver BC Canada Medical Research: What is the background for this study? What are the main findings? Dr. Boyle : Little is known about what causes non-Hodgkin lymphoma (NHL), so trying to identify risk factors is particularly important for the prevention and control of this cancer. There is really good evidence that people who are physically active have a lower risk of some cancers (such as colon and breast cancers), but not many studies have investigated whether being physical active is associated with the risk of non-Hodgkin lymphoma. The key finding of this case-control study was that study participants who were in the higher (second, third, and fourth) quartiles of vigorously intense physical activity performance in their lifetimes had about 25 percent to 30 percent lower risk for NHL, compared with those who were in the lowest (first) quartile of vigorously intense physical activity. (more…)