Author Interviews, Biomarkers, Breast Cancer / 20.03.2016

MedicalResearch.com Interview with: Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer. Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them. (more…)
Author Interviews, Breast Cancer, Lancet / 18.03.2016

MedicalResearch.com Interview with: Professor Jack Cuzick, PhD, FMedSci, FRCP(hon) Director, Wolfson Institute of Preventive Medicine and Head, Centre for Cancer Prevention Queen Mary University of London. MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cuzick: Ductal carcinoma in situ (DCIS) is a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year. Our IBIS-II DCIS trial looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery. The two groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant. The similar NSABP B-35  trial found a 29% reduction with anastrozole and the combined analysis of the two trials indicated a significant 21% reduction. The key difference between the two groups were in the side effects of the medication. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However more fractures and musculoskeletal side effects were seen among those receiving anastrozole. (more…)
Alcohol, Author Interviews, Breast Cancer, Genetic Research, PLoS / 18.03.2016

MedicalResearch.com Interview with: Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) Houston, TX 77204-5056  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers. (more…)
Author Interviews, Breast Cancer / 14.03.2016

MedicalResearch.com Interview with: Professor Nigel Bundred MD, FRCS Professor of Surgical Oncology Institute of Cancer Sciences University Hospital of South Manchester MedicalResearch.com: What is the background for this study? Dr. Bundred: HER-2 is a cancer-causing gene which is expressed in some cells by having more copies of the gene and predicts for early relapse and metastasis from the tumour. Despite this, even in the absence of anything other than local treatment, some 50% of patients still survive for five years without relapse. Herceptin was discovered and licensed for use in 2006 because it improved survival when given with chemotherapy after surgery, from 66% at five years to 90% at five years. The use of Herceptin and chemotherapy before surgery to shrink the tumour indicates that around 30% of patients have a complete pathological response with this treatment. Combination of dual anti-HER-2 therapies and  Neoadjuvant chemotherapy given for six months before surgery has been shown to increase pCR rate to 50% and a single study utilising the combination of pertuzumab and trastuzumab (two anti-HER-2 monoclonal antibodies) given for four months revealed a 16.8% pCR rate. (more…)
Author Interviews, Breast Cancer, Diabetes / 09.03.2016

MedicalResearch.com Interview with: Dr. Zorana Andersen Department of Public Health Center for Epidemiology and Screening University of Copenhagen  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Andersen: Diabetes is associated with increased risk of breast cancer, but exact mechanisms are unknown. The role of insulin has been debated. High mammographic density (MD) is one of the strongest predictors and a biomarker of breast cancer risk. Few studies have linked diabetes to mammographic density, finding none or weak inverse associations, but none had data on diabetes treatment. We examined whether diabetes and diabetes treatment are associated with mammographic density in a prospective cohort study of Danish women above age of 50 years. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Andersen: Women with diabetes, as well as clinicians working with diabetes and breast cancer and breast cancer screening, would have interest to know how different diabetes treatment can affect breast density, and hereby possibly breast cancer risk. For example, diabetic women taking insulin may possibly benefit from informing radiologists at breast cancer screening about their insulin use, due to increased breast density and increased risk of masking bias. (more…)
Author Interviews, Biomarkers, Breast Cancer / 09.03.2016

MedicalResearch.com Interview with: Michele Orditura MD, PhD Associate Professor in Medical Oncology Faculty of Medicine, Second University of Naples Naples Italy  MedicalResearch.com: What is the background for this study? Prof. Orditura: In the last few years increasing evidence suggests that cancer-related inflammatory response plays a crucial role in the development and progression of several malignancies. Neutrophil to lymphocyte ratio (NLR), calculated as the neutrophil count divided by the lymphocyte count , may represent an easily measurable and inexpensive marker of systemic inflammation. Several studies have reported NLR as an unfavourable prognostic indicator for patients with gastrointestinal, lung, renal and gynaecological cancers. In the breast cancer setting, the results of published trials evaluating the relationship between NLR and outcome are controversial, and a recent meta-analysis including eight trials published between 2012 and 2014 has shown that elevated NLR is strongly associated with poor survival. In addition, the available data mainly concern women of Asian race and only three papers have included patients of Europe race. The main aim of this study was to clarify the correlation between pre surgery NLR and distant metastasis-free survival in a series of 300 Italian patients with early breast cancer. The propensity score-matched analysis was chosen for statistical evaluation to avoid risk of confounding bias. (more…)
Author Interviews, Breast Cancer, FASEB / 07.03.2016

MedicalResearch.com Interview with: Michelle L. Halls BBiomedSci(Hons), PhD NHMRC Career Development Fellow Drug Discovery Biology Theme Monash Institute of Pharmaceutical Sciences Monash University Parkville Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Halls: Stress causes an increase in the release of hormones including adrenaline. Previous studies have found a link between stress and metastases in triple negative breast cancer. However, what occurs inside a cancer cell in response to adrenaline to drive cancer progression was not known. We have found that adrenaline can directly act on triple negative breast cancer tumour cells via a cell surface receptor called the beta2-adrenoceptor. We identified changes in signalling within the cell that make the tumour cell highly invasive by mapping the signalling pathways that were activated in these cells in response to stress. We found that different signalling pathways converge to amplify the final signal. This ‘positive signalling loop’ was linked to the increased invasion of these cells in response to stress, and was not identified in less aggressive breast cancer cells. This may allow future research to identify new ways to intervene and slow cancer progression. New therapies are important for triple negative breast cancer, as it is particularly aggressive and currently has limited treatment options. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research / 06.03.2016

MedicalResearch.com Interview with: Rong Li, Ph.D., Professor Holder of the Tom C. & H. Frost Endowment Department of Molecular Medicine Institute of Biotechnology Co-Leader, Cancer Development and Progression Program Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Li: The breast cancer susceptibility gene BRCA1 is well known for its function in double strand break DNA repair. However, the ubiquitous role of BRCA1 in DNA repair may not be sufficient to explain its tissue-specific tumor suppressor function in vivo. Using the “awesome power” of mouse genetics, we identified a previously unappreciated crosstalk between BRCA1 and a transcription regulator in mammary gland development. Importantly, we provide compelling evidence that this BRCA1 function is independent of its well-established DNA repair activity. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Li: The newly identified DNA repair-independent function of BRCA1 may provide new tools and targets for early prevention of BRCA1-associated breast cancer. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2016

MedicalResearch.com Interview with: Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.  (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology / 03.03.2016

MedicalResearch.com Interview with: Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany MedicalResearch.com: What is the background for this study? Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients. For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk. MedicalResearch.com: What are the main findings? Dr. Gluz: The study has two major findings: We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67). Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up. (more…)
Author Interviews, Breast Cancer, Cancer Research, JNCI, Lymphoma / 03.03.2016

MedicalResearch.com Interview with: David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Toronto, ON Canada   MedicalResearch.com: What is the background for this study? Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance. MedicalResearch.com: What are the main findings? Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have "false positive" tests - abnormal findings that are not really cancer. (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, University of Michigan / 28.02.2016

MedicalResearch.com Interview with: Sarah T. Hawley PhD MPH Professor of Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Hawley: Research has shown that breast cancer patients do not have a good understanding of their risk of distant recurrence, and and that the fear of cancer spreading is one of the biggest concerns that patients have. The research that has been done shows that most patients over-esimate this risk, and think they have a bigger chance of the cancer coming back than they actually have. There has been relatively little done to investigate the association between patient over-estimation of risk and patient reported outcomes, specifically their quality of life. We therefore conducted our study to understand the extent of overestimation of risk in a population-based sample of breast cancer patients with very favorable prognosis (DCIS, low risk invasive breast cancer) using a numeric (number based) and descriptive (general understanding) measure, and to understand the association between over-estimation and quality of life. The main findings are that almost 40% of our sample of patients over-estimated their risk; 33% using a numeric measure and 15% using a descriptive measure. There was no clear “type” of patient who overestimated her risk of distant recurrence, though women with lower education more over overestimated numerically than those with higher education. Both numeric and descriptive over-estimation was associated with reduced quality of life outcomes, especially with frequency of worry about recurrence, however over estimating descriptively mattered the most. Women who overestimated their risk both numerically and descriptively had a nearly 10 fold odds of frequent worry compared to women who understood their risk. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations. (more…)
Author Interviews, Breast Cancer, JAMA, Outcomes & Safety, Surgical Research / 17.02.2016

MedicalResearch.com Interview with: Dr. Art Sedrakyan MD PhD ScD Professor of Healthcare Policy and Research in Cardiothoracic Surgery Department of Public Health Weill Cornell Medical College  Medical Research: What is the background for this study? What are the main findings? Dr. Sedrakyan: In the most recent years available to us for research(2011-2013) one in four women underwent repeat surgery within 90 days after breast conserving approach to cancer removal. Patients operated by higher volume physicians had lower chance of undergoing repeat surgery.Uniform guidelines and increased surgical training are needed to standardize the breast conserving surgery to reduce the high rate of repeat surgery. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pancreatic, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal  Medical Research: What is the background for this study? What are the main findings? Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression. We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects. Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients. (more…)
Anesthesiology, Author Interviews, Breast Cancer, Duke, Radiology / 11.02.2016

MedicalResearch.com Interview with: Mary Scott Soo, M.D. FACR Associate professor of Radiology Duke Cancer Institute Medical Research: What is the background for this study? Dr. Soo: Imaging-guided needle breast biopsies for diagnosing suspicious breast lesions have been performed for many years and have definite advantages as a diagnostic tool over surgical biopsies. These biopsies are performed in outpatient settings, which decrease costs and reduce delays, and are highly accurate and less invasive than surgical procedures, requiring only local anesthesia. However, performing biopsies in this outpatient setting limits the use of intravenous sedation and pain medication that could address commonly experienced patient anxiety and occasional associated pain. Anxiety and pain can negatively impact the patient's experience and could possibly affect the biopsy outcome due to patient movement, and could potentially even alter patients' adherence to follow-up recommendations. Prior studies have explored methods to reduce anxiety, using interventions such as music, hypnosis and anxiolytics. Although hypnosis and anxiolytics are effective, these are a little more complicated to implement due to training costs for administering hypnotherapy, and costs, potential side effects, and need for an adult driver to take the patients home when anxiolytics are used. Other research has shown that meditation-based interventions can lead to positive psychological and physical outcomes, and may be helpful for decreasing anxiety, pain and fatigue. Loving-kindness mediation is a type of mediation that focuses on relaxation and developing positive emotions, by silently repeating phrases encouraging compassion and goodwill towards oneself and others, while also reducing negative emotions. Previous studies have shown that even a 7-minute loving-kindness meditation can be effective for increasing positive emotions, so my co-authors Rebecca Shelby PhD, a clinical psychologist at Duke’s Pain Prevention and Treatment Research Program,clinical psychologist Anava Wrenn PhD, who has used loving-kindness meditation in a different practice setting, and breast imaging radiologist Jennifer Jarosz MD and I put together a team to study whether an audio-recorded, lovingkindness meditation could reduce anxiety, fatigue and pain during the imaging-guided breast biopsy time frame.  We consulted with Mary Brantley, MA, LMFT, who teaches loving-kindness meditation at Duke's Integrative Medicine, to develop an audio-recorded loving-kindness mediation used specifically in the breast biopsy setting, and compared this to using music during biopsies or standard care (supportive dialogue) from the technologist and radiologist performing the biopsy. (more…)
Author Interviews, Breast Cancer, Radiation Therapy / 29.01.2016

MedicalResearch.com Interview with: Quyen Chu, MD, MBA, FACS Charles Knight Professor in Surgery Professor of Surgery Chief, Surgical Oncology Director, Surface Malignancies Program Feist-Weiller Cancer Center Louisiana State University Health Sciences Center, Shreveport Medical Research: What is the background for this study? What are the main findings? Dr. Chu: In 2004, national treatment recommendations changed for a select group of elderly breast cancer patients with the Cancer and Leukemia Group B (CALGB) 9343 trial. Research found that postoperative radiation therapy was not needed to prolong survival in a select group of women 70 or older, mainly those with a small, estrogen receptor (ER) positive tumor, and receiving anti-hormone therapy.  Even with this information, nearly two thirds of the women who fit these criteria were still receiving radiation therapy after undergoing a lumpectomy although it has been proven to be safe to omit. We found that as a nation, we are mostly not following the national guideline on breast cancer treatment and that the possible side effects of RT can be avoided. Medical Research: What should clinicians and patients take away from your report? Dr. Chu: Clinicians and patients should take away from this report that in U.S. women 70 or older with stage I, ER+ breast cancer and receiving anti-hormone therapy, radiation therapy is overly utilized as it is not needed to prolong survival.   (more…)
Author Interviews, Breast Cancer, Cancer Research, JAMA, Prostate Cancer / 23.01.2016

More on Cancer Research on MedicalResearch.com MedicalResearch.com Interview with: Firas Abdollah, M.D., F.E.B.U. (Fellow of European Board of Urology) Urology Fellow with the Center for Outcomes Research, Analytics and Evaluation Vattikuti Urology Institute at Henry Ford Hospital in Detroit  MedicalResearch: What is the background for this study? What are the main findings? Dr. Abdollah: Cancer screening aims to detect tumors early, before they become symptomatic. Evidence suggests that detection and treatment of early-stage tumors may reduce cancer mortality among screened individuals. Despite this potential benefit, screening programs may also cause harm. Notably, screening may identify low-risk indolent tumors that would never become clinically evident in the absence of screening (overdiagnosis), subjecting patients to the harms of unnecessary treatment. Such considerations are central to screening for prostate and breast cancers, the most prevalent solid tumors in men and women, respectively. These tumors are often slow growing, and guidelines recommend against screening (non-recommended screening) for these tumors in individuals with limited life expectancy, i.e. those with a life expectancy less than 10 years. Unfortunately, our study found that this practice is not uncommon in the US. Using a nationwide representative survey conducted in 2012, we found that among 149,514 individuals 65 years or older, 76,419 (51.1%) received any prostate/breast screening. Among these, 23,532 (30.8%) individuals had a life expectancy of less than 10 years. These numbers imply that among the screened population over 65 years old, almost one in three individuals received a non-recommended screening. This corresponds to an overall rate of non-recommended screening of 15.7% (23,532 of 149,514 individuals). Another important finding of our study was that there were important variations in the rate of non-recommended screening from state to state; i.e. the chance of an individual older than 65 to receive a non-recommended screening varies based on his/her geographical location in United States. Finally, on a state-by-state level, there was a correlation (40%) between non-recommended screening for prostate and breast cancer, i.e. states that are more likely to offer non-recommended screening for prostate cancer are also more likely to offer non-recommended screening for breast cancer, and vice versa. (more…)
Author Interviews, Breast Cancer, Genetic Research, NYU / 16.01.2016

More on Breast Cancer Research on MedicalResearch.com MedicalResearch.com Interview with: Dr. Benjamin Neel MD PhD Professor, Department of Medicine Director Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Neel:  Over the past 10 years, there have been major advances in cancer genomics--i.e., defining what changes in genes are found in different types of cancer cells.  Sometimes, such studies have resulted in the identification of new drug targets, such as EGF receptor mutations or EML-ALK translocations in lung cancer, RAF mutations in melanoma and hairy cell leukemia, and KIT or PDGFR mutations in GIST.  More often, though, either the genetic changes that genomic studies reveal are difficult to target by conventional small molecule drugs or we dont know which of the many mutations found in a given tumor are critical to its proliferation/survival. "Functional genomics" is a parallel approach to tumor genomics, that aims to use large scale screening technology to identify which genes are essential to cancer cell survival/proliferation.  This approach can reveal which genetic changes in cancer cells "drive" the cancer--but it also can find genes on which the cancer becomes dependent because of the other "driver" genes.  One major approach to functional genomics uses short hairpin RNAs (a type of RNAinterference/RNAi) to "knock down" the expression of each gene in a cell.  Scientists can generate a "library" of designer virus particles, each of which expresses a different hairpin that can "knockdown" a different gene.  A large population of tumor cells is then infected with the virus, and scientists use gene sequencing or array based approaches to see which shRNAs become depleted from the starting population of shRNAs; this type of screen is called a "dropout screen". Earlier studies, including by our group, performed dropout screens on smaller numbers of cancer cell lines.  Yet because these screens involved only a few cell lines, they could not represent the large number of sub-types knownt to occur in, for example, breast cancer.  Our study, by using 77 breast cancer lines, has adequate power to survey the landscape of breast cancer. Furthermore, by obtaining parallel genomic information, as well as some information on the breast cancer cell "proteome" (the proteins in these cells), we can couple genomic analysis with functional genomics. In addition, we had drug response information for a large number of these lines, and so were able to make some predictions for drugs that might prove additive for breast cancer therapy. The result is a large number of potential new targets linked to genetic information, as well as new insights into how the different sub-types of breast cancer "rewire" their respective signaling diagrams compared with normal cells. (more…)
Author Interviews, Breast Cancer, Nature, University Texas / 13.01.2016

Click Here for More Articles Related To Breast Cancer on MedicalResearch.com. MedicalResearch.com Interview with: Dr. Chunru Lin PhD Assistant Professor, Department of Molecular and Cellular Oncology, Division of Basic Science Research and Graduate School of Biomedical Sciences The University of Texas MD Anderson Cancer Center, Houston, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Lin: Triple-Negative Breast Cancer (TNBC) continues to be a serious healthcare problem despite improvements in early detection and treatment; lncRNAs are one of the emerging elements that make the process of understanding breast cancer development and progression so complex yet thorough. Thus, it is imperative to include an examination of lncRNAs when studying breast cancer, especially when researching challenging questions related to relapses and recurrences of breast cancer that occur after targeted therapeutic treatments. A perspective that incorporates lncRNAs into the discussion of breast cancer biology could be the conceptual advance that is necessary to encourage further breakthroughs. Our research reveals the biological functional roles of cytoplasmic lncRNAs as signaling pathway mediators and catalysts that serve as indispensable components of signal transduction cascades and gene networks. This understanding could transform the prevailing dogma of the field of signal transduction. This study has identified a previously unknown mechanism for HIF stabilization and signal transduction, which is triggered by the HB-EGF bound EGFR/GPNMB heterodimer and is mediated by LINK-A-dependent recruitment of two kinases, BRK and LRRK2, to phosphorylate HIF1α at two new sites, leading to HIF1α stabilization and interaction with p300 for transcriptional activation; this further results in cancer glycolytic reprogramming under normoxic conditions. LINK-A is the first demonstrated lncRNA that acts as a key mediator of biological signaling pathways, which suggests the potential for the involvement of other lncRNAs as mediators of numerous signaling pathways. Importantly, expression of LINK-A and activation of the LINK-A mediated signaling pathway are both correlated with TNBC. Targeting LINK-A with LNAs (Locked Nucleic Acids) serves as an encouraging strategy to block reprogramming of glucose metabolism in TNBC with therapeutic potential.  (more…)
Annals Internal Medicine, Author Interviews, Breast Cancer, Mammograms / 12.01.2016

MedicalResearch.com Interview with: Susan K. Boolbol, MD, FACS Chief, Division of Breast Surgery Chief, Appel-Venet Comprehensive Breast Service Co-Director, Breast Surgery Fellowship Mount Sinai Beth Israel Associate Professor of Surgery Icahn School of Medicine at Mount Sinai New York, NY 10003 Medical Research: What is the background for these new recommendations? Dr. Boolbol: To make this final recommendation, the Task Force conducted a comprehensive review of the science since its 2009 recommendation and considered the public comments it received on its 2015 draft recommendation statement. Based on all of this, the task force issued their recommendations. Medical Research: What are the main changes from current guidelines? Dr. Boolbol: Presently, there are several different guidelines and recommendations regarding screening mammography. Depending on the group issuing the guidelines, the recommendations vary from annual mammography beginning at 40 years old to biennial mammograms from 50 to 74 years old. The Task Force continues to find that the benefit of mammography increases with age, and recommends biennial screening in women ages 50 to 74. (more…)
Author Interviews, Breast Cancer, Geriatrics, Mammograms / 07.01.2016

MedicalResearch.com Interview with: Professor Charles Hennekens MD Dr.P.H Sir Richard Doll Professor Senior Academic Advisor to the Dean Charles E. Schmidt College of Medicine Florida Atlantic University 777 Glades Road Boca Raton, FL 33431 Medical Research: What is the background for this study? What are the main findings? Prof. Hennekens: Randomized evidence indicates clear benefits of mammography in middle age and, at present, most guidelines recommend regular mammography for women up to age 74.  In collaboration with colleagues at Baylor Medical College and Meharry Medical School we were able to link the Surveillance, Epidemiology, and End Results (SEER) data to the Medicare administrative claims data.  We found that, up to 84 years, screening was more common among whites than blacks and women receiving regular annual screening mammography had lower risks of mortality from breast cancer. (more…)
Author Interviews, Breast Cancer, Immunotherapy, PLoS / 02.01.2016

MedicalResearch.com Interview with: David Gallego Ortega, PhD Group Leader, Tumour Development Group Cancer Division Garvan Institute of Medical Research Conjoint Lecturer, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Australia National Breast Cancer Foundation and Cure Cancer Foundation Australia Fellow  Medical Research: What is the background for this study? What are the main findings? Dr. Ortega: We have identified a protein that 'goes rogue’ in breast cancer. The protein, called Elf5, ‘tricks' the immune system producing inflammation so that the immune cells now help the breast cancer cells to spread throughout the body. Cancer spread, or metastasis, is the ultimate cause of death of breast cancer patients, so we are very excited about our discovery because it opens the door to explore anti-inflammatory drugs that can be combined with existing therapies. We have found that luminal breast cancer patients that present high levels of Elf5 progress earlier in their disease. The Luminal subtype is the most common type of breast cancer, so these therapies will potentially benefit to 2/3 of all breast cancer patients. (more…)
Author Interviews, Breast Cancer, Stem Cells / 29.12.2015

MedicalResearch.com Interview with: Jenny C. Chang, M.D. Director, Houston Methodist Cancer Center Professor of Medicine, Weill Cornell Medical College Full Member, Houston Methodist Research Institute Houston, Texas  MedicalResearch: What is the background for this study? What are the main findings? Dr. Chang: The current treatment of triple negative breast cancer, which accounts for about 15% of all cases of breast cancer, is still based on surgery, radiotherapy, and classic chemotherapy because, unlike other types of breast cancer, it is not amenable to hormonal or targeted therapy. However, research findings suggest that cancer stem cells, which represent about 2% of all neoplastic cells, may play a role in disease relapses and the formation of distant metastases. As these cells may represent a therapeutic target, the aim of this study is to modify the micro-environment in which they reproduce by acting directly on the chemokines involved in inflammation because there is evidence indicating a possible mechanism of action of reparixin, a molecule developed by Dompé, an Italian biopharmaceutical company, in the targeted treatment of these cancers. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA / 24.12.2015

MedicalResearch.com Interview with: Filippo Montemurro, M.D. Director, Investigative Clinical Oncology (INCO) Fondazione del Piemonte per l'Oncologia Candiolo Cancer Institute (IRCCS) Torino, Italy Medical Research: What is the background for this study? Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The "indirectness" of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended. Based on these premises, we designed a study to pursue two aims;
  • the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
  • the second was to compare doctors and patients reports of toxicities at corresponding time-points.
Medical Research: What are the main findings? Dr. Montemurro: We administered the 10-item questionnaire after the first and third cycle of adjuvant chemotherapy to 601 women who had undergone surgery for breast cancer. To develop this questionnaire, CTCAE definitions of severity for each item (nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea) were translated into Italian and rephrased into statements. Patients were asked to choose the statement that best represented the worst experience with that side effect after the reference cycle of chemotherapy. At the same time-points, research nurses extracted information from the medical charts and reported them in paired doctor questionnaires. A total of 99% and 97% of the patient returned filled in questionnaires. Pairwise comparisons showed that doctors systematically underestimated both incidence and severity for all the side effects. Interestingly, comparison of the two patient questionnaires revealed temporal changes that were possibly related to the effect of prophylactic measures taken after the first cycle (i.e. reduction in vomiting, diarrhea and pain) or to cumulative toxicties (i.e. worsening dysgeusia and dyspnea). No such changes except for worsening dyspnea were observed comparing the two doctors questionnaires. Finally, we found a direct relationship between number of patients and magnitude of discrepancy in side effects reporting was observed, suggesting that the workload could be a factor influencing this phenomenon. (more…)
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology / 23.12.2015

MedicalResearch.com Interview with: Dr. Marjanka Schmidt PhD Group Leader, Molecular Pathology Netherlands Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Schmidt: BRCA1/2 mutation carriers who developed a primary breast cancer are thought to be at high risk to develop a contralateral breast cancer (breast cancer in the opposite breast). Our study is one of the first to provide unbiased risk estimates for young breast cancer patients with a pathogenic BRCA1/2 mutation. We also showed that age of onset of the first breast cancer is a predictor for the development of contralateral breast cancer in BRCA1/2 mutation carriers, but not in non-carriers. (more…)
Author Interviews, Breast Cancer, Cancer Research, Dental Research, Smoking / 21.12.2015

MedicalResearch.com Interview with: Jo Freudenheim, PhD UB Distinguished Professor and Interim Chair Department of Epidemiology and Environmental Health School of Public Health and Health Professions University at Buffalo Buffalo, NY Medical Research: What is the background for this study? What are the main findings? Dr. Freudenheim: There have been a number of studies that have shown an association between periodontal disease and chronic diseases, particularly stroke and heart attacks. There is also some newer evidence that periodontal disease is associated with cancer, particularly cancers of the gastrointestinal tract. Ours is the first large prospective study of periodontal disease and breast cancer. This was part of a study of more than 70,000 postmenopausal women from throughout the United States, the Women’s Health Initiative. Women provided information about their health and other related factors and then those women were followed to see who developed certain diseases. We found that women who had been told that they had periodontal disease were more likely to develop breast cancer. In particular, women who were former smokers (quit within the last 20 years) and who had periodontal disease were at increased breast cancer risk. There was a similar increase in risk for current smokers with periodontal disease but it was not statistically significant. (There was a relatively small number of current smokers in the WHI study.) (more…)
Author Interviews, Breast Cancer, Cancer Research, Depression / 17.12.2015

MedicalResearch.com Interview with: Ruhi Kanani  Cancer Epidemiology and Population Health Research Oncology King's College London London, UK  MedicalResearch.com: What is the background of this study? What are the main findings? Response: There is a long history of research investigating the possible association between psychological and physical health. This study is the first to analyse cancer registration information and hospital records of depression for a large group of women with breast cancer in South East England. 77, 173 women diagnosed with breast cancer between 2000 and 2009 were included and followed until the end of 2010. 955 women had a record of depression, 422 before, and 533 in the year after their cancer diagnosis. The results showed that women with a record of depression had a worse overall survival. This was particularly so for those with a  new record of depression after the cancer diagnosis, who had a 45% higher risk of death from all causes compared to those who didn’t develop depression after their cancer diagnosis. (more…)
Aging, Author Interviews, Breast Cancer / 16.12.2015

MedicalResearch.com Interview with: Susan K. Boolbol, MD, FACS Chief, Division of Breast Surgery Chief, Appel-Venet Comprehensive Breast Service Co-Director, Breast Surgery Fellowship Mount Sinai Beth Israel Associate Professor of Surgery Icahn School of Medicine at Mount Sinai New York, NY 10003  Medical Research: What is the background for this study? What are the main findings? Dr.Boolbol:  The background for this study is predicated on the USPSTF's recommendations that there is insufficient evidence to continue the use of screening mammography in women over the age of 75. According to the American College of Radiology, cancer detection rates via screening mammography should be at least 2.5 per 1000 mammograms at an institution, with reported rates as high as 4.7 cases per 1000. We reviewed 2057 screening mammograms in women aged 75 and older. We found 10 cases of breast cancer in this group. Of these cancers, 60% were invasive breast cancer. The breast cancer detection rate in this cohort was 4.9 per 1000 screening mammograms. (more…)
Author Interviews, Breast Cancer, Chemotherapy, University Texas / 14.12.2015

MedicalResearch.com Interview with: Mariana Chavez Mac Gregor, MD, MSC Assistant Professor Breast Medical Oncology Department Health Services Research Department The University of Texas MD Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Chavez Mac Gregor: Adjuvant chemotherapy has proven to significantly decrease the risk of recurrence among breast cancer patients, however the optimal time to start adjuvant chemotherpay remains unknown. There are biological resasons to believe that a delay in the initiation of systemic therapy can be associated with adverse outcomes. In this large study we evaluated the impact of a delay in the initiation of time to chemotherapy (TTC).  We analyzed data from 24,843 patients with invasive breast cancer (stages I to III) from the California Cancer Registry and observed that compared with patients who received chemotherapy within 31 days of surgery,  no adverse outcomes were associated with time to chemotherapy of 31 to 90 days of surgery. However, there was  a 34 % increase in the risk of death and a 27% increase in the risk of breast cancer specific death  among patients who started  chemotherapy 91 or more days after surgery. In a stratified analysis according to breast cancer subtype, patients with triple-negative breast cancer, a TTC greater than 91 days  was  significantly  associated with worse overall and breast cancer-specific survival. In addition we evaluated factors associated with delays in  time to chemotherapy (defined as > or = 91 days) and observed that many of the factors are sociodemographic in nature including low socioeconomic status, non-private insurance, and being Hispanic or African American. (more…)