Author Interviews, BMJ, Breast Cancer, Cancer Research / 07.10.2015

Dr. Madeleine M A Tilanus-Linthorst PhD Department of Surgery Erasmus University Medical Centre - Cancer Institute Rotterdam, NetherlandsMedicalResearch.com Interview with: Dr. Madeleine M A Tilanus-Linthorst PhD Department of Surgery Erasmus University Medical Centre - Cancer Institute Rotterdam, Netherlands  Medical Research: What is the background for this study? Medical Research: Why is this study important? Response: This prospective nationwide study  investigates whether  tumor stage (size and axillary nodal involvement)  still has impact on survival of breast cancer in modern times with more effective end more widely used additional systemic therapy . We  take tumour biology, age and the different therapies into account and compare results with our nationwide results from 1999-2005.   
  1. Mortality increased with increasing tumour size and independently with nodal involvement, correcting for age, tumour biology and therapy.
  2. Five year relative survival (this is compared with women without breast cancer of the same ages) was 96% for all 93.569 Dutch breast cancer patients between 2006-2012 and 100% in cancers ≤ 1cm.3.     In 2006-2012 in the Dutch population 65% of the breast cancers were detected ≤2cm.
Medical Research: What should clinicians and patients take away from your report?
  1. First, the general prospect of a woman diagnosed with breast cancer currently in the Western world is very good.
  2. Catching breast cancer early is still highly important.
  3. Surgery is the cornerstone of therapy and maybe breast conserving therapy is even a bit better for survival than mastectomy and certainly not worse. Breast cancer in the other breast did not impact on survival and preventive contralateral mastectomy seems only well advised in high risk gene mutation carriers.
  4. Both additional hormonal therapy and targeted therapy (usual against epidermal growth factor her2neu) are, if indicated by tumour stage and receptor status, beneficial for survival.
  5. Further also patients diagnosed late with large tumors of 5cm and above experienced an improvement in outcome. In the earlier group such patients had a 70% five-year relative survival, while in the recent cohort this increased to 81%. This may be a comforting result for some patients.
  6. Finally our results are informative when considering breast  screening.
Author Interviews, Breast Cancer, Surgical Research / 04.10.2015

Kimberly J. Van Zee, MD, FACS Surgical oncologist Memorial Sloan-Kettering Cancer MedicalResearch.com Interview with: Kimberly J. Van Zee, MD, FACS Surgical oncologist Memorial Sloan-Kettering Cancer Medical Research: Why is this study important? Dr. Van Zee: It is very important because the 4 large studies that randomized women with DCIS to radiation or not after they had breast-conserving surgery all began between 1985 and 1990.  Those studies are generally used to help women and clinicians estimate risk of subsequent recurrence in the same breast over time.  This study shows that recurrence rates have significantly fallen over the decades, suggesting that the recurrence rates observed in those studies are higher than what would be expected in the current era.  This is good news for women that want to have breast conservation for DCIS! Medical Research: What are the key findings? Dr. Van Zee:
  1. a)       Recurrence rates have fallen over the years, by about 40% between the early period (1978-1998) and the later period (1999-2010).
  2. b)      The decrease in recurrence rates is only partly explained by factors such as increased screening, wider margins, more frequent use of endocrine therapy (ie, tamoxifen).
  3. c)       The improvement in recurrence rates is mostly due to a decrease in recurrence rates for women NOT undergoing radiation (even though women having radiation continue to have a lower recurrence rate than those not having radiation)
  4. d)      This last point is important because since radiation is given only to reduce local recurrence rates and has never been shown to improve survival (survival is excellent with all treatments).  So a woman treated currently with breast conservation without radiation can expect about a  40% lower recurrence rate than in the earlier decades.
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, NEJM / 29.09.2015

Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer CenterMedicalResearch.com Interview with: Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Miller: Previous studies had found a small but real benefit with the addition of chemotherapy to anti-estrogen treatment in patients with hormone sensitive disease. The challenge for patients and clinicians has always been that the benefit of chemotherapy is quite small and the toxicity can be substantial. The Oncotype Dx recurrence score assay was developed to identify patients who could safely be treated with anti-estrogen therapy alone (and conversely those who truly need and would derive a much larger benefit from chemotherapy). When the Oncotype Dx RS was applied to samples stored from a previous randomized trial, patients with low risk scores didn't seem to benefit from chemotherapy. While those initial results had some impact on treatment, many were concerned about eliminating chemotherapy on the basis of one small retrospective trial. The overall trial enrolled 10,253 women. 1626 (15.9%) had a Recurrence Score of 0-10 and were assigned to receive antiestrogen therapy alone without chemotherapy. After five years 99.3% (98.7, 99.6%) for were free of distant relapse (that is to say, 99.3% of women had NOT had recurrence of breast cancer at distant sites in the body). Overall survival was 98%.
Author Interviews, Breast Cancer, JNCI / 21.09.2015

Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892MedicalResearch.com Interview with: Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892  Medical Research: What is the background for this study? What are the main findings? Dr. Rosenberg: It has been previously reported that breast cancer burden (number of new cases diagnosed in a year) is expected to rise in the future, mostly due to the aging of the female population in the US. Also, it has been established that the age-adjusted breast cancer incidence rates (cases per 100,000 women per year) are increasing for invasive ER-positive cancers overall and decreasing for ER-negative cancers overall. When taken together, these two trends tend balance each other out, resulting in a somewhat flat breast cancer incidence rate overall.  Though the overall trends for invasive breast cancer have been previously reported, this study uses a more refined forecasting method by including recent birth cohort patterns to forecast breast cancer to 2030 by age group, estrogen receptor-status, and invasive vs. in situ tumors. New in this report are the findings for in situ tumors and the more granular break down by age, ER status, and invasive vs. in situ tumors both for rate and burden (number of cases).
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Genetic Research, Journal Clinical Oncology, Race/Ethnic Diversity / 20.09.2015

Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114MedicalResearch.com Interview with: Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114   Medical Research: What is the background for this study? What are the main findings? Response:  Multiple studies have consistently shown that African American women with cancer, including breast cancer, have worse outcomes than Caucasian counterparts. While socioeconomic issues, including access to care plays an important role, the contribution of tumor biology has been less clear. In this study, utilizing exome sequencing data, we linked the racial distribution of primary breast cancer with tumor genotypic traits, including somatic mutations, gene-expression profiles and intra-tumor heterogeneity. We observed that in addition to having a higher prevalence of triple negative breast cancer than Caucasian women (something that has been documented in the literature), African American women had a significantly higher prevalence of TP53 mutations, TNBC basal-like 1 and mesenchymal stem-like tumors, and intratumor genetic heterogeneity, and all of which suggest more aggressive tumor biology, suggesting that differences in tumor genomic profile contribute, at least partly, to the known racial disparity in survival between African Americans and Caucasians breast cancer patients.
Author Interviews, Breast Cancer, JAMA, Mediterranean Diet / 14.09.2015

MedicalResearch.com Interview with: Miguel Ángel Martínez González MD Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid IdiSNA, Navarra Institute for Health Research, Pamplona, Navarra, Spain Medical Research: What is the background for this study? Response: Several observational studies and mechanistic experiments in animal models and cell lines suggested that the Mediterranean diet and minor components of extra-virgin olive oil may reduce the risk of developing breast cancer. The PREDIMED study was a randomized primary prevention trial for cardiovascular disease among high risk patients initially free of cardiovascular disease. The participants were 7,447 men and women (60-80 years old). We have used the data from women in this trial to assess the effect of the randomized diets on the occurrence of new cases of breast cancer. Medical Research: What are the main findings? Response: Among 4,152 women randomized to 3 different diets (1.- Mediterranean diet with free provision of extra-virgin​ olive oil; 2.- Mediterranean diet with free provision of tree nuts; and 3.- Advice to follow a low-fat diet, i.e. control group) We confirmed 35 new cases of invasive breast cancer during 4.8 of follow-up. A statistically significant 68% relative reduction in the risk of breast cancer in the Mediterranean diet with free provision of extra-virgin​ olive oil versus the control group was found. There was a significant trend of risk reduction associated with progressive increments in the intake of extra-virgin olive oil during the trial (with repeated yearly measurements of diet) when the 3 groups were assessed together.
Author Interviews, Breast Cancer, Genetic Research, UCSF / 04.09.2015

Dr. Elisa Long PhD Assistant professor UCLA Anderson School of ManagementMedicalResearch.com Interview with: Dr. Elisa Long PhD Assistant professor UCLA Anderson School of Management Medical Research: What is the background for this study? What are the main findings? Dr. Long: The study was motivated by my own diagnosis of triple-negative breast cancer last year, at the age of 33. I also learned that I carried a BRCA1 mutation, despite no family history. As a patient, I would have benefitted tremendously from a universal BRCA screening program, but as a health services researcher, I had to ask if indiscriminate screening of all women in the U.S.—where only 1 in 400 carry a mutation—is a good use of resources. Using a previously published decision analytic model, we calculated the cost-effectiveness of universal BRCA screening. We find that compared to screening based on family history, it is not cost-effective, assuming a test price of $2,000 to $4,000. However, as the price of genetic testing continues to fall, as indicated by the $249 test now offered by Color Genomics, universal BRCA screening becomes much more affordable. Additionally, population screening of Ashkenazi Jewish women—among whom 1 in 50 carry a BRCA mutation—is very cost-effective, because the chances of finding a carrier are much higher.
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Surgical Research / 01.09.2015

Dr. Rachel A Freedman MD MPH Assistant Professor of Medicine Harvard Medical SchoolMedicalResearch.com Interview with: Dr. Rachel A Freedman MD MPH Dana-Farber Cancer Institute Assistant Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Despite a lack of medical benefit for most patients, the rates for bilateral mastectomy (double mastectomy) are on the rise in the U.S. Many factors have been cited as potential reasons for this increase, such as one’s race/ethnicity, education level, family history, and use of MRI. Cancer stage has not consistently been a factor in past studies. In this study, we surveyed 487 women who were treated for breast cancer in Northern California within the California Cancer Registry, we examined factors associated with the type of surgery a woman received. In our study, we found strong associations for stage III cancer with receipt of unilateral and bilateral mastectomy. In addition, higher (vs. lower) income and older age were associated with lower odds of having bilateral surgery.
Author Interviews, Breast Cancer, NIH, Weight Research / 31.08.2015

Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health ScienceMedicalResearch.com Interview with: Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health Science MedicalResearch: What is the background for this study? Dr. White: Many studies have shown that being overweight or obese is a risk factor for postmenopausal breast cancer. We know less about how obesity impacts breast cancer risk in premenopausal women. About a third of U.S. adults are obese, which is defined as having a body mass index (BMI) greater than 30. Similarly, the prevalence of abdominal obesity, measured by a person’s waist circumference, has increased by 10% in the last decade. In 2012, more than two-thirds of U.S. women had a waist circumference that indicated abdominal obesity. Abdominal obesity may be a better predictor than BMI for breast cancer risk and other chronic diseases, because it is related to insulin resistance and can reflect metabolically active fat stores. In order to understand how different types of obesity (overall vs. abdominal) influence breast cancer risk, we used information from >50,000 participants in the Sister Study. The Sister Study, led by scientists at the National Institute of Environmental Health Sciences, part of the National Institutes of Health investigates environmental and genetic risk factors for breast cancer.
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 27.08.2015

Michaela Ann Dinan Ph.D. Assistant Professor in Medicine Member of Duke Cancer Institute Duke University School of MedicinMedicalResearch.com Interview with: Michaela Ann Dinan Ph.D. Assistant Professor in Medicine Member of Duke Cancer Institute Duke University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Dinan: For many years we have known that overall, women with early stage, hormone receptor positive breast cancer show an overall survival benefit from the receipt of adjuvant chemotherapy.  However, depending on the age of the patient, we have also known that between 3 to 10% of patients appear to be truly experiencing this survival benefit and that we are treating a lot of women unnecessarily.  The use of the Oncotype DX assay has provided additional information for patients to assess who at low risk of disease progression and can forgo chemotherapy. In this study we looked to see whether the adoption of this assay was associated with reduce rates of chemotherapy in women over the age of 65.  We found that somewhat surprisingly, there was no overall association with receipt of the assay and use of chemotherapy.  However, in women who had high risk disease, receipt of the assay was associated with reduced rates of chemotherapy use.  In patients with low risk disease, receipt of the assay was associated with increased chemotherapy use.
Author Interviews, Breast Cancer, Genetic Research, Race/Ethnic Diversity / 26.08.2015

Tuya Pal MD Division of Population Sciences Department of Health Outcomes and Behavior Moffitt Cancer Center Tampa, Florida MedicalResearch.com Interview with: Tuya Pal MD Division of Population Sciences Department of Health Outcomes and Behavior Moffitt Cancer Center Tampa, Florida   Medical Research: What is the background for this study? Dr. Pal:  Young Black women bear a disproportionate burden associated with breast cancer incidence and mortality compared to their White counterparts. Given that inherited mutations in the BRCA1 and BRCA2 genes are more common among young breast cancer survivors, we questioned to what extent mutations in these genes might contribute to the racial disparity in breast cancer incidence among young women. Medical Research: What are the main findings? Dr. Pal:  Through conducting the largest U.S. based study of BRCA mutation frequency in young black women diagnosed with breast cancer at or below age 50, we discovered they have a much higher BRCA mutation frequency than that previously reported among young white women with breast cancer.  Specifically, of the 396 Black women with breast cancer diagnosed at or below age 50, 12.4% had mutations in either BRCA1 or BRCA2.  Furthermore, over 40 percent of those with a mutation had no close relatives with breast or ovarian cancer, which suggests that family history alone may not identify those at risk for carrying a BRCA mutation. 
Anesthesiology, Author Interviews, Breast Cancer, Journal Clinical Oncology, Surgical Research / 19.08.2015

Jaclyn Bradley Palmer, MM, MT-BC University Hospitals Of Cleveland Cleveland, OHMedicalResearch.com Interview with: Jaclyn Bradley Palmer, MM, MT-BC University Hospitals Of Cleveland Cleveland, OH  Medical Research: What is the background for this study? What are the main findings? Response: Patients awaiting breast cancer surgery may be understandably anxious. While pharmacologic intervention may reduce anxiety, higher doses of preoperative drugs can depress circulation and respiration, making alternative measures a particular interest. Music therapy is the clinical use of music interventions to accomplish individualized goals within a therapeutic relationship by a board-certified music therapist. While music in surgery has been researched under the label of "music therapy", many of the studied investigations illicit recorded music provided by non-music therapy staff, making it truly "music medicine" practices instead. In this investigation, the effect of both live and recorded music therapy on anxiety, anesthesia requirements, recovery time and patient satisfaction were studied perioperatively. Breast cancer surgery patients were engaged in a brief music therapy session which consisted of one live or recorded preferred song choice, followed by discussion and processing of emotions. Compared to usual care, both live and recorded music therapy groups experienced significantly greater reductions in anxiety (p<.001) with point reductions of 27.5 (42.5%) and 26.7 (41.2%), respectively. During surgery, both music groups listened to music-therapist selected recorded, instrumental harp music, chosen for it's evidence-based therapeutic value of smooth lines, consistent volumes and stable melodies. In measuring the amount of interoperative drug (propofol) needed to reach moderate sedation, the intraoperative music was not found to have an effect in this trial. Patient satisfaction was universally high in all three study groups. Those who received live music preoperatively were discharged an average of 12.5 minutes sooner than those who received recorded music preoperatively, although neither music group was dischanged significantly sooner than the control group. Subjective reactions to the music interventions relayed that music therapy in surgery was an enjoyable addition.
Author Interviews, Breast Cancer, NEJM, Radiation Therapy / 14.08.2015

MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands  Medical Research: What is the background for this study?   Dr. Poortmans:  Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.  Medical Research: What are the main findings?  Dr. Poortmans:  We found a decreased risk for development of distant metastases of 3% at 10 years, translated in a 3% overall improved overall disease free survival. Up to now, It leads to an improvement of 1.6% in overall survival at 10 years, which is, in contrast to the earlier 2 findings, just not statistically significant (borderline at p = 0.06). On the other hand, breast cancer related mortality is significantly improved and we did not see an increase in non breast cancer related causes of death. Overall toxicity was limited with only a significant increase in pulmonary toxicity, however to a low grade in the big majority of those patients. The benefit in overall survival is in a similar order of magnitude than adding for example taxanes to anthracycline-based adjuvant chemotherapy for a similar patient population as ours.  Medical Research: What should clinicians and patients take away from your report? Dr. Poortmans:     First, we should appreciated that the regional (lymph node) recurrence rate is a poor endpoint for evaluation of also locoregional treatment. This can be explained by the fact that once distant metastases are found, no further search for local (breast) or regional (lymph nodes) recurrences is performed any more, as this is not relevant anymore for treatment or prognosis. However, the spread of distant metastases might occur from cancer involvement of the lymph nodes, explaining why we saw the effect of the lymph node irradiation basically only on the rate of development of distant metastases.     As a second message, we can appreciate that the 3% decreased distant metastases rate did not yet fully translate into a survival benefit, which can be explained by the need for even longer follow-up than 10 years. The explanation lies simply in the fact that even after development of distant metastases, patients can live for quite some more years with, however, only very little chance for definitive cure.     Thirdly, we demonstrated with the quality assurance programme linked to this trial that radiation treatment as used those days (the accrual phase was from 1996 until January 2004) radiation therapy techniques should be nowadays considered as suboptimal with a lack of full coverage of the target volumes and delivery of a too high dose to the organs at risk. With modern techniques, we expect that the results will even be quite better.     And finally, that the overall outcome of breast cancer improved a lot: at the start of the trial, we estimated overall survival at 10 years being 50%, which we revised in 2000 to 75% and we ended up with more than 80%. Thereby, it becomes more of a challenge to demonstrate benefits of further improving treatment as the same relative improvement will be translated into a lower absolute improvement. Nevertheless, by more effectively preventing the development of distant metastases by improved systemic therapy (or even better by earlier detection with a lower basal rate of distant metastases) the importance of optimizing locoregional control becomes even higher.   Medical Research: What recommendations do you have for future research as a result of this study?  Dr. Poortmans:   o	First of all we have to improve our ability to define which patients will gain most from this treatment.  o	Secondly, we have to further investigate how to optimize the technical aspects of this loco regional treatment and … o	Thirdly how to optimally integrate all treatment aspects including locoregional ones and systemic ones.  o	Based on all this, we can develop and then provide the patients with shared decision making tools.    Citation: Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer Philip M. Poortmans, Ph.D., Sandra Collette, M.Sc., Carine Kirkove, Ph.D., Erik Van Limbergen, Ph.D., Volker Budach, Ph.D., Henk Struikmans, Ph.D., Laurence Collette, Ph.D., Alain Fourquet, Ph.D., Philippe Maingon, M.D., Mariacarla Valli, M.D., Karin De Winter, M.D., Simone Marnitz, M.D., Isabelle Barillot, Ph.D., Luciano Scandolaro, M.D., Ernest Vonk, M.D., Carla Rodenhuis, Ph.D., Hugo Marsiglia, Ph.D., Nicola Weidner, Ph.D., Geertjan van Tienhoven, Ph.D., Christoph Glanzmann, Ph.D., Abraham Kuten, M.D., Rodrigo Arriagada, M.D., Harry Bartelink, Ph.D., and Walter Van den Bogaert, Ph.D. for the EORTC Radiation Oncology and Breast Cancer Groups N Engl J Med 2015; 373:317-327 July 23, 2015 DOI: 10.1056/NEJMoa1415369       MedicalResearch.com is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Philip.Poortmans@radboudumc.nl MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands   Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.
Author Interviews, Breast Cancer, Genetic Research, JAMA, Ovarian Cancer / 13.08.2015

Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center  Boston, MA 02114MedicalResearch.com Interview with: Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific. Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families.  Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family.
Author Interviews, Biomarkers, Breast Cancer / 11.08.2015

Dr Stephen Chan DM, FRCR, FRCP Consultant Oncologist Breast and Gynaecological Cancers Nottingham University Hospitals Trust Honorary Professor at the University of Nottingham Visiting Professor of Cancer Medicine at Nottingham Trent UniversityMedicalResearch.com Interview with: Dr Stephen Chan DM, FRCR, FRCP Consultant Oncologist Breast and Gynaecological Cancers Nottingham University Hospitals Trust Honorary Professor at the University of Nottingham Visiting Professor of Cancer Medicine at Nottingham Trent University MedicalResearch: What is the background for this study? What are the main findings? Dr. Chan: Worldwide each year 1.68 million women are diagnosed with breast cancer and more than half a million die from the disease. Of these new cases around 12% will be classified as triple negative breast cancer (TNBC), meaning that tumour cells from these patients do not show any of the three established clinical markers that can be treated with targeted therapies. These drugs are used in addition to standard chemotherapy to improve the chance of a good treatment response, leading to prolonged disease free survival. Without these additional treatment options triple negative patients are forced to depend entirely on chemotherapy to treat their cancer. Traditionally the sensitivity of a cancer to different types of chemotherapy has been categorised is based on a tumours tissue of origin and stage. There is currently no predictive marker of response that would allow chemotherapy treatment to be tailored to individual patients. With this information a clinician can predict which patients would benefit most from a particular chemotherapy and switch any who would do poorly to an alternative. The result would be a shift to increased treatment efficacy, while avoiding toxicity from ineffective treatment, which would in turn also reduce the cost to the health service. This need is particularly acute in triple negative breast cancer cases where chemotherapy is the cornerstone of treatment. In collaboration with researchers based at Nottingham Trent University our group has been successful in finding new markers, which can predict how a patient will respond to chemotherapy treatment. One of these is HAGE (DDX43), a DEAD box RNA helicase. We have found that high HAGE expression predicts good respond to one of the main first line chemotherapy drugs, called anthracycline (Tarek MA Abdel-Fatah et al, April 2014). Our recent work (Tarek MA Abdel-Fatah, 2015) has shown that the predictive value is strong in triple negative breast cancer cases.
Author Interviews, Biomarkers, Breast Cancer / 30.07.2015

Karla M. Gonye, MBA President, sphingotec LLC Cambridge, MassachusettsMedicalResearch.com Interview with: Karla M. Gonye, MBA President, sphingotec LLC Cambridge, Massachusetts MedicalResearch: What is the background for this study? Response:
  • Met- and Leu-Enkephalin: are endogenous pentapeptides of the family of opioid peptides known as opiod-growth factors (OGF)
  • Enkephalins have been widely studied and play a major role in a variety of physiological processes
    • Perception of pain
    • Regulation of stress
    • Regulation of cardiovascular function
    • Regulation of bone formation
    • Regulation of immune responses
  • Alcohol and pain relievers reduce synthesis of Enkephalins
  • Met-Enkephalin (opioid growth factor) inhibits tumor progression and metastasis and enhances natural killer cell activity1,2
  • Mechanisms3-7:
    • Opioids can directly interact with tumor cells to cause a cytotoxic or antiproliferative effect
    • Opioids can modulate host antitumor immune mechanisms
  • Opiods can also induce apoptosis
  • We need enkephalins to help inhibit tumor progression
  • At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that reduced enkephalins in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure enkephalin.
  • This method is published in a separate publication by Ernst et al (2006) in Peptides.
  • To test this hypothesis, Sphingotec measured enkephalin levels in the MDC and MPP study populations to determine if an association could be made between lower enkephalins and risk of breast cancer: We related proenkephalin (P-ENK) in fasting plasma from 1929 healthy women (mean age 58±5.9 years) of the population based Malmö Diet and Cancer Study (MDCS) to incidence of breast cancer (n=123) using multivariate Cox proportional hazards models during 14.8 years of follow-up. For replication, P-ENK was related to risk of breast cancer (n=130) in an older independent sample from the Malmö Preventive Project (MPP) consisting of 1569 women (mean age 70.0±4.4 years), using multivariate logistic regression.
Author Interviews, Biomarkers, Breast Cancer / 29.07.2015

Karla M. Gonye, MBA President, sphingotec LLC Cambridge, MassachusettsMedicalResearch.com Interview with: Karla M. Gonye, MBA President, Sphingotec LLC Cambridge, Massachusetts MedicalResearch: What is the background for this study? Response:
  • In experimental studies, Neurotensin and neurotensin expression was highly associated to breast cancer tissue
    • Dupouy et al (2009) investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal carcinomas (IDCs) and found that NTS is expressed in ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade 3 (p<0.05), larger tumor size (p<0.01), and the number of metastatic lymph nodes (p<0.05).
    • It was concluded from this paper that NTS/NTSR1 is a contributor to breast cancer progression.
    • Souaze et al (2006)also studied IDCs and found 34% of all tumors were positive for neurotensin and 91% positive for the NT1 receptor, suggesting the contribution of neurotensin’s involvement in the signaling cascade within breast cancer progression.  In this study, it was found that disruption of neurotensin receptor signaling by silencing RNA or using a specific NT1 antagonist in nude mice xenografted with an aggressive cell line SR48692, caused the reversion of transforming functions that lead to tumor growth.
    • These findings support the contribution of neurotensin to breast cancer progression.
    • Wu, Z. et al (2013) reviewed the contribution of the neurotensinergic system to cancer progression, as well as the regulation and mechanisms of the system in order to highlight its potential as a therapeutic target, and its prospect for its use as a treatment in certain cancers.
    • This summarizes nicely the oncogenic effects of neurotensin after stimulation signaling proliferation, survival, migration, invasion and neoangeogeneis.
    • Several other papers published demonstrate the effects of neurotensin in cancers including breast cancer.
    • New studies such as Roselli et al (2015) further demonstrate the role of neurotensin in aggressive breast cancer.
    • At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that elevated expression of neurotensin in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure neurotensin.
    • This method is published in Ernst et al (2006) in Peptides.
    • To test the hypothesis, the first clinical study was conducted in a cohort of normal healthy population that was indentified from the Malmo Diet and Cancer study, a prospective epidemiological study of 28,449 men and women. Of this group, a subset of 4632 randomly selected subjects were identified and neurotensin was measured in all subjects. Subjects were adjusted for known breast cancer risk factors such as age, age of menarche, heredity of cancer (all), hormone status, etc. (see Table 3, Melander et al JAMA 2012) so that the factors did not influence outcomes. On a 10-15 follow up period, of these subjects, 123 breast cancer events were found to be associated with higher levels of neurotensin, with the highest quartile associated with the highest levels of neurotensin and the lowest quartile associated with the lowest levels of neurotensin. The association of elevated neurotensin was found to be statistically significant for prediction of breast cancer.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Sexual Health / 29.07.2015

Martha F. Goetsch, MD, MPH Oregon Health & Science University Portland, OR 97239MedicalResearch.com Interview with: Martha F. Goetsch, MD, MPH Oregon Health & Science University Portland, OR 97239 MedicalResearch: What is the background for this study? Dr. Goetsch: Women who are survivors of breast cancer now number about 3 million in the US.  Therapy for breast cancer is anchored in creating a state of postmenopause in which estrogen is eliminated from the system. One of the most difficult symptoms of lack of estrogen is dyspareunia, the term for pain with intercourse. The old term “vulvovaginal atrophy” has been changed to “genitourinary syndrome of menopause” by agreement of two specialty societies. Because of my focus in the gynecologic specialty of vulvar pain, I have felt that this menopausal symptom is more than a condition of atrophy.  Additionally, my clinical experience has led me to believe that the exquisite tenderness is located in the vulvar vestibule rather than in the vagina. The vestibule is the inner vulva or entryway before the vagina. This study was devised to answer these hypotheses. I predicted that the population most likely to represent the worst examples of postmenopausal dyspareunia was the population of women who cannot use estrogen due to being survivors of breast cancer. I treated the problem as a pain problem rather than solely a problem of dryness.
Author Interviews, Breast Cancer, Journal Clinical Oncology, NIH / 24.07.2015

Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780MedicalResearch.com Interview with: Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780 Medical Research: What is the background for this study? Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the  trends in age- and stage-specific breast cancer death rates after diagnosis. We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ.  We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant). Medical Research: What are the main findings? Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter.  For women under age 70, rates also fell for women with distant disease. Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis.
Author Interviews, Breast Cancer, Journal Clinical Oncology, Race/Ethnic Diversity / 21.07.2015

Helmneh Sineshaw, MD, MPH Senior Epidemiologist, Health Services Researcher American Cancer Society, Inc Atlanta, GA 30303MedicalResearch.com Interview with: Helmneh Sineshaw, MD, MPH Senior Epidemiologist, Health Services Researcher American Cancer Society, Inc Atlanta, GA 30303 MedicalResearch: What is the background for this study? Dr. Sineshaw: Male breast cancer is a rare disease, and its incidence rate is increasing. Younger black men have a higher breast cancer incidence than their white counterparts. Although black/white disparities in treatment receipt and survival among women with breast cancer have been widely documented in the literature, there have been few similar studies in men with breast cancer. Previous studies were based on smaller sample size, older databases, or using data from elderly patients.
Author Interviews, Breast Cancer, Radiology / 21.07.2015

Alison L. Chetlen, D.O. Associate Professor, Department of Radiology Penn State Milton S. Hershey Medical Center Hershey, PA 17033MedicalResearch.com Interview with: Alison L. Chetlen, D.O. Associate Professor, Department of Radiology Penn State Milton S. Hershey Medical Center Hershey, PA 17033 Medical Research: What is the background for this study? Dr. Chetlen:  Breast cancer risk assessment provides a means of identifying women who are at risk for development of this disease.   Identifying individuals at high risk for breast cancer allows for genetic testing, supplemental breast cancer screening, possibly prophylactic surgery or chemoprevention in hopes of decreasing mortality from breast cancer.  Despite the advantages of cancer genetic risk assessment and testing, most individuals in the general population who would benefit from such services currently do not receive them.  Medical Research: What are the main findings? Dr. Chetlen:  After implementation of a specific high-risk recommendation within our standardized mammography report along with a letter written in “lay” language informing patients of their high-risk status, the number of referrals to our high-risk clinic increased only modestly.   Despite these specific recommendations to both physicians and patients, over 85% of high risk patients did not consult a high-risk provider regarding their elevated lifetime risk of breast cancer.
Author Interviews, Breast Cancer / 20.07.2015

Niels de Jonge, Ph.D Head of the Innovative Electron Microscopy group German Cancer Research Center (DKFZ) in Heidelberg University of FreiburgMedicalResearch.com Interview with: Niels de Jonge, Ph.D Head of the Innovative Electron Microscopy group German Cancer Research Center (DKFZ) in Heidelberg University of Freiburg Medical Research: What is the background for this study? What are the main findings? Response: HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood. We now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth.
Author Interviews, Breast Cancer, Cancer Research, Nutrition / 16.07.2015

Dr. Vincent L. Cryns MD Chief of the Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Wisconsin Carbone Cancer Center University of Wisconsin School of Medicine and Public Health Madison, WisconsinMedicalResearch.com Interview with: Dr. Vincent L. Cryns MD Chief of the Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Wisconsin Carbone Cancer Center University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Medical Research: What is the background for this study? What are the main findings? Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or die. What’s been missing is a molecular explanation for these effects that would allow us incorporate this approach into a rationally designed clinical trial. In our work, we have demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a “fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a targeted cancer therapy.
Author Interviews, Breast Cancer, Endocrinology, Lancet, Menopause / 08.07.2015

MedicalResearch.com Interview with: Dr. Jürg Bernhard Ph.D. International Breast Cancer Study Group Coordinating Center and Bern University Hospital, Inselspital, Bern, Switzerland Medical Research: What is the background for this study? What are the main findings? Response: In the combined analysis of the SOFT and TEXT trials, the aromatase inhibitor exemestane was more effective than tamoxifen in preventing breast cancer recurrence in young women (premenopausal) who also receive ovarian function suppression (OFS) as adjuvant (post-surgery) treatment for hormone-sensitive early breast cancer, providing a new treatment option for these women. These trials were conducted by the International Breast Cancer Study Group (IBCSG) and involved more than 4700 patients of over 500 centers in 27 countries. Now we present patient-reported quality of life outcomes from these trials. In the TEXT and SOFT trials, patients assigned exemestane+OFS reported more detrimental effects of bone or joint pain, vaginal dryness, greater loss of sexual interest and difficulties becoming aroused, while patients assigned tamoxifen+OFS were more affected by hot flushes and sweats. Global quality of life domains (mood, ability to cope and physical well-being) were similar between the randomized treatment groups.
Author Interviews, Breast Cancer, Radiation Therapy, UCLA / 01.07.2015

Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CAMedicalResearch.com Interview with: Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Kamrava: Breast conservation (lumpectomy followed by radiation) is known, based on multiple randomized trials with over 20 years of follow-up, to provided equivalent outcomes as mastectomy.  The radiation component of breast conservation has standardly been delivered to the whole breast.  Studies show that the majority of breast recurrences occur near the lumpectomy cavity causing some to ask whether it is necessary to treat the whole breast in order to reduce the risk of a recurrence. Partial breast radiation delivers treatment just to the lumpectomy cavity with a small margin of 1-2 cm.  It’s delivered in a shorter time of 1 week compared with about 6 weeks for standard whole breast radiation and 3-4 weeks for hypofractionated whole breast radiation. The original method developed to deliver partial breast radiation is interstitial tube and button brachytherapy.  This uses multiple small little tubes that are placed through the lumpectomy cavity to encompass the area at risk.  One end of these tubes can be connected to a high dose rate brachytherapy machine that allows a motorized cable with a very small radiation source welded to the end of it to be temporarily pushed in and out of each of the tubes so that the patient can be treated from “inside out”.  This helps concentrate the radiation to the area of the lumpectomy cavity while limiting exposure to normal tissues.  This treatment is most commonly delivered as an out-patient two times per day for a total of 10 treatments. The main finding from our paper is that in reviewing the outcomes on over 1,000 women treated with this technique with an average follow-up of 6.9 years that the 10 year actuarial local recurrence rate was 7.6% and in women with more than 5 years of follow-up physician reported cosmetic outcomes were excellent/good in 84% of cases.
Author Interviews, Biomarkers, Breast Cancer / 21.06.2015

MedicalResearch.com Interview with: Kristian Pietras, Ph.D. Göran & Birgitta Grosskopf Professor of Molecular Medicine Strategic Director of Cancer Research Lund University Dept of Laboratory Medicine Lund Div of Translational Cancer Research Lund, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Pietras: Breast cancer is the largest malignant disease among women with 1.7 million new cases worldwide each year (25% of all new cancer cases for women). The prognosis for breast cancer patients is relatively good when the disease is detected at early stages (close to 90% of patients are still alive 5 years after diagnosis). Nevertheless, metastatic disease is the cause of 90% of all cancer-related deaths. Thus, learning more about the metastatic process and finding new cures for widespread disease is justifiably at the center of clinical attention. The current study is part of our ongoing efforts to map support functions performed by the various cell types comprising the tumor stroma with the premise that decisive treatment benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that collectively sustain the growth of tumors. The development of a rich vascular supply  is recognized as a key hallmark of a growing tumor necessary for the development into a clinically relevant disease. Our focus is the role of the tumor vasculature in preventing or promoting metastatic dissemination from the primary tumor. For a metastasis to form, a cancer cell must, 1) detach from its neighboring cells in the mother tumor, 2) traverse the vascular wall to escape into the blood stream, 3) exit the vasculature to enter the metastatic site, and 4) colonize the metastatic site. Recent evidence points to that the transmigration into and out of the vasculature is a regulated process of previously unrecognized importance for the metastatic process. Importantly, the fact that the process of escape into/from the vasculature is regulated also implies that it is possible to use drugs to block this process. In the present study, we have combined functional studies in advanced models of cancer and computational biology approaches to investigate the specific contribution to the metastatic process of a molecular signaling pathway emanating from the ALK1 protein expressed by endothelial cells in the vasculature. Using information from 2 different patient cohorts including a total of  nearly 2000 breast tumors, we found that patients specifically having high levels of ALK1 in the vasculature of their tumor were much more likely to develop metastatic/recurrent disease. Accordingly, therapeutic administration of a drug (dalantercept) blocking the action of ALK1 prevented metastatic dissemination in multiple mouse models of breast cancer to a large degree. In addition, combination therapy of dalantercept and a commonly used chemotherapeutic drug (docetaxel) was exceedingly effective in preventing spread of the primary tumor to the lungs. Our results suggest that the molecular features of the tumor vasculature are important to consider as potential determinants of breast cancer dissemination and that metastatic spread can be delayed by targeting the tumor vasculature.
Author Interviews, Breast Cancer, JAMA, Race/Ethnic Diversity, Surgical Research, University Texas / 21.06.2015

Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TXMedicalResearch.com Interview with: Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns.
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 11.06.2015

Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North CarolinaMedicalResearch.com Interview with: Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer.  The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients.