Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Cancer / 28.01.2015

Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, MassachusettsMedicalResearch.com Interview with: Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases.
Author Interviews, Breast Cancer, Karolinski Institute / 26.01.2015

Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, SwedenMedicalResearch.com Interview with: Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes.
Author Interviews, Breast Cancer, Scripps / 25.01.2015

Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, FloridaMedicalResearch.com Interview with: Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Griffin: We identified a novel synthetic compound known as SR1848 that sharply inhibits the activity and expression of “liver receptor homolog-1” or LRH-1, a protein that plays an important role in the progression of breast and pancreatic cancers. Our new study shows that SR1848 removes LRH1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation. It’s a novel compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies.
Author Interviews, Breast Cancer, Nutrition / 19.01.2015

Cecilia Cesa Schiavon Department of Nutrition, Federal University of Santa Catarina Florianópolis, Santa Catarina, BrazilMedicalResearch.com Interview with: Cecilia Cesa Schiavon Department of Nutrition, Federal University of Santa Catarina Florianópolis, Santa Catarina, Brazil Medical Research: What is the background for this study? What are the main findings? Response: The study was based on a nutritional intervention for patients undergoing treatment for breast cancer. The intervention took place right after the surgical procedure and lasted about a year, until the end of chemotherapy. The patients were submitted to a special methodology of intervention, aimed at increasing fruit and vegetable intake and reducing red and processed meat, following the World Cancer Research Fund and the American Institute for Cancer Research in the document entitled Food, Nutrition, Physical Activity and the prevention of Cancer: A Global Perspective”. The main findings show that women undergoing breast cancer treatment may benefit from immediate, individualized, and detailed nutrition monitoring through appropriate nutrition education.
Author Interviews, Breast Cancer, Inflammation / 16.01.2015

Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City MéxicoMedicalResearch.com Interview with: Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City México MedicalResearch: What is the background for this study? Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders.
Author Interviews, Breast Cancer, JAMA / 14.01.2015

Javaid Iqbal, MD, MSC (Candidate) Institute of Medical Sciences, and Women’s College Research Institute/Women’s College Hospital University of Toronto, Toronto CanadaMedicalResearch.com Interview with: Javaid Iqbal, MD, MSC (Candidate) Institute of Medical Sciences, and Women’s College Research Institute/Women’s College Hospital University of Toronto, Toronto Canada What is the background for this study? What are the main findings? Dr. Iqbal: A woman’s racial/ethnic background predicts her participation in breast cancer control program (i.e., awareness and screening). The ultimate objective of breast cancer control program is to detect cancer at an optimal stage, which is stage I, because women with stage I breast cancer survive longer. Given the racial/ethnic diversity of North America, this poses questions such as “what predicts stage I breast cancer in the multiethnic North American population?”, “what predicts its survival?”, and “does a woman’s ethnic background plays a role in predicting an early stage, and survival?” We studied 373,563 women diagnosed with invasive breast cancer in the United States between 2004 and 2011. We followed these women for 7 years and recorded whether or not they died of breast cancer, or whether they are still alive. We then divided all women into different ethnic groups, in particular white, black, Chinese, Japanese, and Indian/Pakistani (South Asian). For each racial/ethnic group, we estimated proportions of women who were diagnosed with stage I breast cancer, and risk of death at 7 years. Our aim was to determine if the racial/ethnic differences in early stage breast cancer, and its survival were better explained by intrinsic biological differences in tumor characteristics, or by differences in early-detection of breast cancer. We found that a woman’s racial/ethnic background predicted the diagnosis of stage I breast cancer, as well as her risk of dying at 7 years after breast cancer. A black woman was less likely than a white woman to be diagnosed with stage I breast cancer. A black woman was also more likely than a white woman to die of stage I breast cancer 7 years after her diagnosis. The Japanese and Chinese women were more likely than white women to be diagnosed with stage I breast cancer. The risk of death at 7 years was lowest for Indian or Pakistani (South Asian) women. Furthermore, even for small sized (2.0) breast cancers the risk of death at 7 years was higher for black women (9%), compared to white women (5%). Compared to white women, small sized breast cancers in black women were more aggressive at diagnosis, and had spread to lymph nodes and other organs.
Author Interviews, Breast Cancer, Genetic Research, Nature / 11.01.2015

MedicalResearch.com Interview with: Dr. Pentao Liu PhD and Dr. Walid Khaled PhD Wellcome Trust Sanger Institute Cambridgeshire United Kingdom Medical Research: What is the background for this study? What are the main findings? Dr. Pentao Liu: The significance of this research is that it aims to tackle the worst type of breast cancer. Triple Negative Breast Cancer (TNBC) has the poorest patient survival rate compared to other forms of breast cancer.  At present there are no targeted therapies available for TNBC, leaving the non-specific chemotherapy as the only treatment option. In this study we identify a new key gene in  Triple Negative Breast Cancer which could potentially be inhibited for the targeted treatment of TNBC. In this study we report the identification of a novel gene for Triple Negative Breast Cancer. By analyzing genomics data from 3,000 patients we find BCL11A to be highly expressed in TNBC. We then demonstrate experimentally that upregulation of BCL11A drives tumour development while its downregulation leads to reduction in tumour size. In the experimental mouse model, inactivation of this gene completely abolishes breast tumour development.
Author Interviews, Breast Cancer, JNCI / 11.01.2015

https://medicalresearch.com/category/hepatitis-liver-disease/page/2/MedicalResearch.com Interview with: Hazel B. Nichols, PhD Assistant Professor, Department of Epidemiology University of North Carolina Gillings School of Global Public Health MedicalResearch:What is the background for this study? Dr. Nichols: Tamoxifen, a drug that is often used to treat breast cancer, has also been approved to prevent breast cancer in women who may be at high risk for developing the disease. Taking tamoxifen for 5 years can lower breast cancer risk by up to 48%. The United States Federal Drug Administration (FDA) approved tamoxifen for breast cancer prevention more than 15 years ago (in 1998) for women ages 35 and older who are at high risk of breast cancer and who are at low risk for serious side effects. National estimates show that <1% of women who are eligible to use tamoxifen actually use it for breast cancer prevention. While tamoxifen lowers breast cancer risk it does cause hot flashes and may lead to serious side effects such as cataract, stroke, and uterine cancer. Women who start taking tamoxifen may also stop taking it before the recommended 5-years due to side effects. We used a tool developed by scientists at the National Cancer Institute (NCI) to calculate whether the benefits of tamoxifen outweighed the risks for women in the Sister Study, a study of more than 50,000 U.S. and Puerto Rican women with a family history of breast cancer. The tool uses information on a woman’s age, race, breast cancer risk, menopausal status, and whether she had a hysterectomy (surgical removal of the uterus) to estimate whether there is no, moderate or strong evidence that the benefits of tamoxifen will outweigh the risks.
Author Interviews, Breast Cancer, Genetic Research / 10.01.2015

Dr. Chao Cheng PhD Department of Genetics Geisel School of Medicine at Dartmouth Hanover 03755, NHMedicalResearch.com Interview with: Dr. Chao Cheng PhD Department of Genetics Geisel School of Medicine at Dartmouth Hanover 03755, NH   MedicalResearch: What is the background for this study? What are the main findings? Dr. Chao Cheng: Cancer survival prognosis—“How long do I have, Dr.?” is a topic of great importance to cancer patients and their families. While clinical and pathological variables, such as cancer type, stage, grade, and patient demographics, have long been used to predict survival outcomes, only recently have molecular signatures become incorporated into survival prediction. A molecular approach holds great promise for improving prediction accuracy and additionally elucidating mechanisms of disease, however it is fraught with difficulty due to assay “noise” and “big data” statistical issues, such as the multiple comparisons problem In this study, we began by analyzing transcription factor binding profiles across available cell lines. By restricting our analysis to transcription factors, DNA expression regulators known to be involved in tumor genesis, we reasoned that we could avoid many of the “big data” issues and achieve results that would make mechanistic and biological sense. We first employed a statistical method we described previously to calculate which genes were the major downstream targets of our transcription factors. With these targets identified, we then analyzed gene expression data using a bioinformatics method to infer the relative activity of each transcription factor based upon the overall expression levels of their gene targets. From here, we incorporated cancer survival data and examined how each transcription factor’s regulatory activity did, or did not, correlate with survival. The most prognostic transcription factor was E2F4, a member of the E2F family and a known regulator of the cell cycle. We therefore restricted our analysis to E2F4 and examined how its activity level impacted survival in breast cancer patients. We found that tumors with high E2F4 regulatory activity as compared to low E2F4 regulatory activity had much worse survival outcomes. These results were stable even after controlling for tumor stage, grade, patient age, and treatment, and were based on data from over 1900 patients across eight independent datasets. These results demonstrate that E2F4 is an independent and enhancing predictor of survival above the currently examined variables.
Author Interviews, Breast Cancer, Geriatrics / 07.01.2015

MedicalResearch.com Interview with: Pamela Vacek, PhD Research Assistant Professor Department of Pathology Medical Biostatistics Unit, College of Medicine University of Vermont,  Burlingon, Vermont Medical Research: What is the background for this study? What are the main findings? Dr. Vacek: Clinical trials to evaluate the effectiveness of screening mammography have focused primarily on women under age 70 and, consequently, its benefit for older women is uncertain. However, many believe that the benefit of screening mammography diminishes as women age and acquire other health problems, because they are less likely to live long enough for any detected breast cancer to have a clinical impact. To gain insight into this, we followed approximately 20,000 women aged 70 and older for an average of 10 years to examine their mammography use, cancer detection and survival. We found that screening mammography use declined steadily (9% per year) after age 70, but this was not accompanied by decline in the incidence of invasive breast cancer. Hence, as the women aged breast cancer was more likely to be detected clinically than by screening. The clinically detected tumors were significantly larger and of more advance stage and were associated with poorer overall survival, for all but the oldest and most infirm women. We also found that the use of breast conserving surgery as the only treatment for early stage cancer increased markedly with age and was associated with shorter survival compared to women receiving radiation or mastectomy.
Author Interviews, Breast Cancer, Mayo Clinic, NEJM / 03.01.2015

MedicalResearch.com Interview with:  Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic  Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings?  Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern  – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined.  As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them.  Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up.  This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort).  This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women.  Medical Research: What should clinicians and patients take away from your report? Dr. Hartmann: There are about 100,000 US women each year diagnosed with atypical hyperplasia via breast biopsy.  Although strictly speaking, atypical hyperplasia is a benign finding, it is associated with a sizable risk of a later breast cancer.  Physicians from numerous disciplines care for women with high-risk benign breast issues, including gynecologists, family physicians, internists, surgeons and oncologists.  These practitioners, and the patients themselves, need information about the absolute risk of breast cancer occurring over time after a diagnosis of atypical hyperplasia.  This information is provided in the NEJM report.  Also, current guidelines should be updated to include this high-risk population and specifics about their absolute risk, and that the risk level qualifies these patients for screening MRI.   Moreover, from the standpoint of risk reduction, four previously conducted breast cancer prevention trials included women with atypical hyperplasia.  These trials used hormonal therapies (anti-estrogens) and showed that, in women with atypical hyperplasia, the use of such medications could lower the risk of a later breast cancer by 50% or more.  Yet, other research has shown that women are quite reluctant to take such medications, primarily because of fear of side effects.  In the NEJM report, we detail specific numbers of side effects that actually occurred in women who used these anti-estrogens (as opposed to the number of side effects seen in women taking placebo) and show that most of the side effects occurred quite uncommonly.  Thus, we hope that the combination of information provided in this report on (i) actual risks of breast cancer and (ii) actual risks of side effects will help patients and practitioners make informed decisions on the best treatment approaches for women with atypical hyperplasia.  Medical Research: What recommendations do you have for future research as a result of this study?  Dr. Hartmann: First, women with atypical hyperplasia should be included in future prospective trials of novel imaging strategies (they were not included in trials of MRI, which had been limited to women with hereditary risk).  Second, efforts should continue to predict which women with atypical hyperplasia are at highest risk, especially in the first 5-10 years after their biopsy, so they can be cared for optimally.  Our research team, and others, continue to study the underlying molecular pathways that drive the progression from atypical hyperplasia to cancer; identifying such processes would not only aid in risk prediction but also identify driving pathways that could be blocked pharmaceutically.   Citation:  upcoming NEJM publication discussing:  Women with Atypical Hyperplasia are at Higher Risk of Breast Cancer MedicalResearch.com Interview with: Dr. Lynn C. Hartmann MD Professor of Oncology, Mayo Clinic Associate Director for Education of the Mayo Clinic Cancer Center. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Women with atypical hyperplasia of the breast – which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern  – have been considered a “high risk” group of women, but the extent of their risk has not been clearly defined.  As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them.  Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up.  This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort).  This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women.
Author Interviews, Breast Cancer / 29.12.2014

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

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

MedicalResearch.com Interview with: Dr Ranjit Manchanda Consultant Gynaecological Oncologist, St Bartholomew’s Hospital, London, UK Honorary Sr Lecturer, Women’s Cancer, EGA Institute for Women's Health, University College London, UK  and Professor Ian Jacobs Vice President, The University of Manchester Dean & Head School of Medicine Faculty of Medical & Human Sciences, Director MAHSC (Manchester Academic Health Science Centre) Medical Research: What is the background for this study? What are the main findings? Dr. Jacobs:  Background- Women carrying a BRCA1/2 gene alteration have a very high risk of developing breast and ovarian cancer and men carrying this alteration have an increased risk of prostate and breast cancer. Approximately 45-65% women who have this inherited genetic change will develop breast cancer and 15-35% ovarian cancer. They also have a 50% chance of passing these genes on to their children. At risk individuals can access available options of screening and prevention through the National Health Service (NHS). Some population groups across the world are known to have a higher frequency of BRCA 1/2 gene alterations than others. One example is Ashkenazi Jews who have a 1 in 40 likelihood of having a BRCA1/2 gene alteration. This is 10-20 times higher than in the general non-Jewish population. At present in the UK, genetic testing is available within the NHS to individuals who have a strong family history of cancer. However, many people are not aware of their family history or its significance and do not seek advice. Many other individuals with BRCA1/2 gene alterations do not have a family history at all. The current approach misses a large number of people at risk who could benefit from knowing about their BRCA 1/2 mutation status and the ability to access opportunities for prevention or screening. In order to address this the GCaPPS study has investigated the best method of screening for risk of inherited (familial) cancer by exploring the alternative approach of offering the genetic test to all men and women >18 years in the Ashkenazi Jewish population. It does so by comparing the benefits and disadvantages of: (i) The current system of testing only those with a family history and (ii) The new option of testing everyone in the population. Main Findings: Over half of the BRCA1/BRCA2 carriers detected did not give a strong family history of cancer and would not have been identified by current family history based testing criteria used in the NHS (National Health Service) in the UK and most health systems internationally. Reassuringly population-based genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life. A health economic analysis indicated that population-based screening for BRCA-mutations in Ashkenazi Jewish women ≥30years would be highly cost-effective compared to the traditional family history based approach. Such an approach if implemented could reduce the incidence of and deaths from breast and ovarian cancer as well as reducing cost and save the NHS funds.
Breast Cancer / 20.12.2014

Thomas Rogers PhD Candidate- Cancer Biology Graduate Program Laboratory of Jennifer Richer Department of Pathology University of Colorado-Anschutz Medical Campus Laboratory of CU Cancer Center investigator, Jennifer Richer, PhD.MedicalResearch.com Interview with: Thomas Rogers PhD Candidate- Cancer Biology Graduate Program Laboratory of Jennifer Richer Department of Pathology University of Colorado-Anschutz Medical Campus Laboratory of CU Cancer Center investigator, Jennifer Richer, PhD. Medical Research: What is the background for this study? What are the main findings? Response: Background: Survival while detached from a basement membrane is a critical trait of cancer cells progressing through the metastatic cascade. This is particularly important for the triple-negative breast cancer (TNBC) subtype, which lacks estrogen and progesterone receptors and does not have amplification of HER2, and has a peak risk of recurrence within the first three years post-diagnosis. Triple-negative breast cancer also has the highest mortality rate in the first five years as compared to other breast cancer subtypes. We performed global profiling of TNBC cells in adherent versus forced suspension culture conditions after24 hours. These data revealed that triple-negative breast cancer cells surviving in suspension upregulate multiple genes involved in tryptophan catabolism, also known as the kynurenine pathway, including the rate limiting enzyme tryptophan 2,3,-dioxygenase (TDO2) and kynureninase (KYNU). Kynurenine, a key intermediate metabolite of this pathway activates the aryl hydrocarbon receptor (AhR), which was also up-regulated in TNBC cells grown in forced-suspension culture. Main Findings: Critical enzymes of the kynurenine pathway, TDO2 and KYNU, are upregulated in triple-negative breast cancer cells grown in forced-suspension culture. Furthermore, secreted kynurenine doubles in TNBC cells in forced-suspension culture as measured by high performance liquid chromatography (HPLC). Kynurenine activates the aryl hydrocarbon receptor in triple-negative breast cancer cells grown in forced-suspension culture. Targeting TDO2 and AhR with small molecule inhibitors or short hairpin RNAs decreased survival in suspension, migration/invasion, and proliferation of TNBC cells. Lastly, TDO2 gene expression is higher in invasive ductal breast carcinoma as compared to normal breast tissue and is significantly higher in estrogen receptor negative tumors as compared to estrogen receptor positive tumors. In addition, patients with higher (above-median) TDO2 expression in their primary tumor had significantly shorter overall survival than those with low TDO2. Conclusions: The kynurenine pathway is activated in TNBC cells in forced suspension and facilitates the invasive/metastatic phenotype of this aggressive breast cancer subtype. Our findings support further investigations into targeting the enzyme TDO2 in TNBC as a novel therapeutic strategy with potential to reduce TNBC mortality rates. Kynurenine is well-known to suppress immune cell function via activation of AhR.
Author Interviews, Breast Cancer, University of Pittsburgh / 17.12.2014

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

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

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

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo ClinicMedicalResearch.com Interview with: Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Dr. Goetz: There has been conflicting data with regard to the importance of tamoxifen metabolism as measured by CYP2D6 genetic variation.   Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy.   Our findings demonstrated that these studies were flawed in part based on analytical validity issues.  In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples.
Author Interviews, Breast Cancer, Yale / 12.12.2014

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

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

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

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

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

Elissa R. Price, MD Assistant Professor of Clinical Radiology Director of Clinical Operations, Breast Imaging Breast Imaging Fellowship Program Director Department of Radiology and Biomedical Imaging University of California, San Francisco San Francisco, CA  94115MedicalResearch.com Interview with: Elissa R. Price, MD Assistant Professor of Clinical Radiology Director of Clinical Operations, Breast Imaging Breast Imaging Fellowship Program Director Department of Radiology and Biomedical Imaging University of California, San Francisco San Francisco, CA  94115 MedicalResearch: What is the background for this study? What are the main findings? Dr. Price: Screening mammography recommendations for the 40 - 49 age group is very controversial. 2009 USPTF guidelines emphasized taking patient context into account when making decisions for these young women. Recent publications have suggested risk-based screening strategies.  Family history and breast density are important are easily accessible risk factors. Had we been using this risk-based approach to screening mammography at our institution, we would have missed more than 3Ž4 of the screen detected breast cancers in the 40-49 age group, thereby foregoing most of the survival benefit from screening mammography.
Author Interviews, Breast Cancer / 28.11.2014

Ben Ho Park, M.D., Ph.D. Associate Professor of Oncology, Breast Cancer Program Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD  21287MedicalResearch.com Interview with: Ben Ho Park, M.D., Ph.D. Associate Professor of Oncology, Breast Cancer Program Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD  21287 Medical Research: What is the background for this study? What are the main findings? Dr. Park: To discover genetic mediators of tamoxifen resistance in breast cancers, we used genetic screening of breast cancer cell line models and patient data to ​identify a new gene that can mediate drug resistance. We found that amplification and overexpression of this gene in estrogen receptor positive breast cancers results in tamoxifen resistance and is associated with worse outcomes in patients whose tumors demonstrate amplification/overexpression of this gene.
Author Interviews, Breast Cancer / 25.11.2014

MedicalResearch.com Interview with Dr. Jonathan Myles Centre for Cancer Prevention, Queen Mary, University of London Wolfson Institute of Preventive Medicine, Charterhouse Square, London Medical Research: What is the background for this study? What are the main findings? Dr. Myles: Breast cancer screening uptake is low in areas of high social deprivation and large populations of some ethnic groups.  The main  finding of this study is that an intervention in the form of contacting women by telephone a few days before the date of their screen, reminding them of their appointment and answering any queries they may have, significantly increases uptake.
Author Interviews, Breast Cancer, JAMA, Surgical Research, Vanderbilt / 20.11.2014

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

MedicalResearch.com: Interview Invitation Dr. Wenji Guo University of Oxford Medical Research: What is the background for this study? Response: Previous studies report increased risk for breast cancer in postmenopausal women who have a higher Body Mass Index (BMI) – a measure of body fat based on height and weight. However, BMI is unable to distinguish between excess weight due to fat rather than muscle. More direct measures of fatness, such as body fat percentage, may be better indicators of disease risk. And although probable evidence for the relationship between physical activity and breast cancer now exists, questions still remain over the role of vigorous compared to lower intensity physical activity.
Author Interviews, Breast Cancer, Case Western, Chemotherapy / 10.11.2014

Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center  Case Western Reserve UniversityMedicalResearch.com Interview with: Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center  Case Western Reserve University Medical Research: What is the background for this study? Dr. Keri: Over the last several decades, the discovery of targeted therapies for certain types of breast cancer, and their use in the clinic, have greatly improved the long-term outcome of patients. Yet some breast cancers don’t respond to these therapies, and ones that do often become resistant over time, resulting in patient relapse and metastatic disease. Why does resistance occur? There are many tricks a tumor employs to evade death. When a drug targets a certain protein or pathway the cancer cell relies on for survival, one potential route of resistance is the cancer cell’s ability to adapt and find another pathway to maintain growth. We reasoned that targeting two separate proteins or pathways important for cancer cell growth may be more effective at preventing or delaying this adaptation.
Author Interviews, Breast Cancer / 06.11.2014

Antoine E. Karnoub, Ph.D. Assistant Professor of Pathology Beth Israel Deaconess Medical Center Harvard Medical School Center for Life Science 0634 Boston, MA 02215MedicalResearch.com Interview with: Antoine E. Karnoub, Ph.D. Assistant Professor of Pathology Beth Israel Deaconess Medical Center Harvard Medical School Center for Life Science 0634 Boston, MA 02215 Medical Research: What are the main findings of the study? Dr. Karnoub: The main findings of the study are: (1) that the metastatic propensities of cancer cells can be remarkably modulated by otherwise ‘normal’ mesenchymal stem/stromal cells found in their vicinity; (2) that generation of highly malignant tumor-initiating cells can be significantly triggered by microenvironmental cues; (3) that repression of the gene FOXP2 by a miR-199a-led microRNA network enables the propagation of cancer stem cell and metastatic traits in otherwise weakly metastatic cancer cells; and (4) that such a signaling axis appears to forecast poor patient outcome.