AACR, Author Interviews, Breast Cancer, Cancer Research, Nutrition / 05.06.2015

MedicalResearch.com Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. Atlanta, Georgia Dr. Wang: Several epidemiologic studies and a recent large pooled analysis suggest that higher blood levels of carotenoids, a group of lipid-soluble pigments that are rich in colorful fruits and vegetables, are associated with lower breast cancer risk. What remains unclear is whether or not the effect of carotenoids on breast cancer differ by estrogen receptor status, tumor stage, BMI, and smoking status. We examined plasma carotenoids and breast cancer risk overall, and by aforementioned tumor and participant characteristics in a cohort of 992 postmenopausal women. We found that higher pre-diagnosis plasma α-carotene, but not other subtypes or total carotenoids, was significantly associated with lower invasive breast cancer risk. The inverse association of α-carotene with breast cancer risk seems stronger for estrogen receptor positive tumors than for estrogen receptor negative tumors. There is a suggestive inverse association of total plasma carotenoid levels and breast cancer among ever smokers but not among never smokers.
Author Interviews, Breast Cancer, JAMA, Leukemia / 03.06.2015

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

Daniel F. Hayes, M.D. Stuart B. Padnos Professor of Breast Cancer Research University of Michigan Comprehensive Cancer Center Ann Arbor MIMedicalResearch.com Interview with: Daniel F. Hayes, M.D. Stuart B. Padnos Professor of Breast Cancer Research University of Michigan Comprehensive Cancer Center Ann Arbor MI Medical Research: What is the background for this study? What are the main findings? Dr. Hayes: We have developed a circulating tumor cell endocrine therapy index that we hypothesize will identify patients with estrogen receptor positive metastatic breast cancer but who will not benefit from endocrine (anti-estrogen) therapy. We can now semi-quantifiably measure er as well as bcl2, her2, and ki67 in a highly accurate and reproducible fashion.  We are now conducting a multi-institutional prospective trial in North America (the Circulating Tumor Cell-Endocrine Therapy COMETI study) to determine if our hypothesis is correct.
ASCO, Author Interviews, Breast Cancer, Cancer Research, NEJM, Surgical Research, Yale / 31.05.2015

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

MedicalResearch.com Interview with: Bruno M. Heleno MD The Research Unit for General Practice and Section of General Practice Department of Public Health University of Copenhagen Medical Research: What is the background for this study? What are the main findings? Dr. Heleno: False positive mammography causes psychological distress. Several observational studies have shown this, and their results have been summarized in systematic reviews. However, it was unclear whether women requiring invasive tests (needle or surgical biopsy) were more distressed than women only requiring non-invasive procedures (clinical examination or imaging). Contrary to previous research, we found that these two groups of women were equally distressed during the 36 months of follow-up in our cohort. The best estimate for the difference for 12 related measures of distress was always close to zero.
Author Interviews, Breast Cancer / 26.05.2015

Professor Ramsey Cutress Associate Professor in Breast Surgery University of SouthamptonMedicalResearch.com Interview with: Professor Ramsey Cutress Associate Professor in Breast Surgery University of Southampton Medical Research: What is the background for this study? What are the main findings? Response: The main finding is that in young women with breast cancer, a breast cancer family history of breast cancer did not affect recurrence rates. This work forms part of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study, which included 2850 women under age 41 years who were diagnosed with breast cancer and treated in the UK. The study, led by principal investigator Professor Diana Eccles, recorded patients’ personal characteristics, tumour characteristics, treatment, and family history of breast/ovarian cancer over a 15-year period.
Author Interviews, Biomarkers, Breast Cancer / 19.05.2015

Lao Saal, M.D. Ph.D.MedicalResearch.com Interview with: Lao Saal, M.D. Ph.D. Head, Translational Oncogenomics Unit Assistant Professor Department of Oncology and Pathology Lund University Cancer Center Lund, Sweden Medical Research: What is the background for this study? Dr. Saal: About a quarter of women diagnosed with primary (non-metastatic) breast cancer will unfortunately progress and later be found to have metastatic spread, which can occur many years to even a decade or more after the first diagnosis. At this point, the prognosis after identification of metastatic breast cancer is very poor. Metastatic disease is typically diagnosed only after it has grown large enough to cause symptoms, be noticed on exam, or be detectable by imaging. It is thought that early detection of metastasis has the potential to lead to better outcomes because therapies could be modified when the metastasis is still very small. Moreover, a very sensitive and specific test that could identify patients who appear "cancer-free" could also be useful. Essentially all cancers have unstable genomes, where chromosomes physically break and are reassembled incorrectly and thus the normal sequence is altered. Importantly, DNA material from cancer cells can be found in the blood circulation and therefore this circulating tumor DNA has the potential to be a cancer biomarker. Medical Research: What are the main findings? Dr. Saal: Eleonor Olsson, a PhD student in my lab who defends her thesis next week, and Christof Winter, a postdoc bioinformatician in my group, were the first authors of the paper. In our study we tested whether periodic monitoring of circulating tumor DNA (ctDNA) in blood plasma samples, taken before surgery for primary breast cancer and at multiple timepoints after surgery, could identify the metastastic spread, and whether the quantity of ctDNA was associated to patient outcome. We analyzed a retrospective cohort of 20 patients, who had enrolled many years ago in a separate epidemiological study run by Helena Jernström in our department, wherein the appropriate blood plasma samples had been biobanked and tumor tissue was available and we had long-term clinical follow-up information. As far as we are aware, our study is the first to show the potential for serial ctDNA monitoring in the context of primary breast cancer. We found that our ctDNA blood tests could discriminate patients with eventual metastasis from those with long‐term disease‐free survival with 93% sensitivity and 100% specificity. Furthermore, ctDNA‐based detection of metastatic disease preceded clinical detection for 86% of patients by an average 11 months and in some cases by 3 years. In all of the patients who had long-term disease-free survival, we did not detect any ctDNA in any timepoints after surgery. Lastly, the measured quantity of ctDNA was a significant predictor of outcome: for each doubling of the ctDNA level, the odds ratio for metastasis was 2.1 and the odds ratio for death was 1.3. An interesting anecdote -- one patient we studied had bilateral breast cancer and we found that it was the right-side tumor (which actually had more favorable clinical characteristics) that gave rise to the metastasis and not the left-side tumor.
Author Interviews, Breast Cancer, Chemotherapy, Journal Clinical Oncology, Stanford / 13.05.2015

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

Stanford, CA 94305-5826
Medical Research: What is the background for this study? What are the main findings? Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC). Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%). Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response.
Author Interviews, Breast Cancer, JNCI, Surgical Research / 11.05.2015

Bernadette A.M. Heemskerk-Gerritsen, Ph.D.		 Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the NetherlandsMedicalResearch.com Interview with: Bernadette A.M. Heemskerk-Gerritsen, Ph.D. Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Heemskerk-Gerritsen: Women with a BRCA1 or BRCA2 mutation have substantially higher risks of developing both primary and contralateral breast cancer (BC) and ovarian cancer than women from the general population. Options to reduce these increased cancer risks include risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). The latter intervention obviously reduces the risk of developing ovarian cancer, but has been reported also to reduce the risk of developing a subsequent breast cancer with approximately 50%. However, studies on the efficacy of risk-reducing surgery in BRCA1/2 mutation carriers are confined to observational studies, thus challenging several methodological issues. Consequently, previous studies on breast cancer risk-reduction after RRSO may have been influenced by bias associated with selection of study subjects, bias associated with start of follow-up, or by confounding, and breast cancer risk-reduction may have been overestimated. In the current study, we revisited the association between risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1/2 mutation carriers, focusing on the impact of different analytical methods and potential types of bias. First, we replicated the analyses of four previously performed studies, to examine if our Dutch cohort was comparable with the cohorts used in the previous studies. We replicated the approximately 50% breast cancer risk reduction after RRSO in the Dutch cohort. Second, we estimated the effect of RRSO on breast cancer risk in the Dutch cohort using a revised analytical approach for observational studies in BRCA1/2 mutation carriers in order to minimize bias as much as possible. Using this method of analysis, we found no evidence of first BC risk-reduction after RRSO in BRCA1/2 mutation carriers.
Author Interviews, Breast Cancer, Case Western, Genetic Research / 07.05.2015

Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineMedicalResearch.com Interview with: Ahmad M. Khalil, PhD Assistant professor, Department of Genetics and Genome Sciences Case Western Reserve University School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Khalil: This study aimed to identify other genes that work synergistically with the oncogene HER2 in HER2positive (HER+) breast cancer. The gene HER2 is amplified in those patients, which results in excess activities that promote uncontrolled cell growth. There are drugs that target HER2 and diminish its activity. However, these drugs can work initially, but patients relapse; or sometimes, the drugs don't work at all in some patients. Thus, by identifying other genes that work synergistically with the HER2 gene, we now have more genes to target by various drugs or compounds to destroy the tumor. The challenge was how to identify the key genes that work synergistically with HER2, especially in human subjects. To that end, we used clinical samples from a clinical trial of a drug that is known to inhibit HER2 activity to identify those genes. To further refine our list, we used cell culture models of the disease to also inhibit HER2. By combining those data sets, we identified 44 protein-coding genes. Next, we wanted to make sure that those genes stand a third independent filter. For that part, we interrogated those 44 genes in HER2+ tumors vs matched normal tissues from The Cancer Genome Atlas database — a collection of hundreds of tumors and normal tissues. Of the 44 genes, 35 genes passed this third filter. By examining the known functions of those genes, we can deduce that those genes work cooperatively with HER2 to promote carcinogenesis. There are currently known drugs that target some of those genes. We will use these drugs in combination with a drug that target HER2 to determine if the combination works better at destroying the tumor entirely. Lastly, we found that a special type of genes that we previously discovered, called lincRNAs, could also affect the oncogenic activity of HER2. These lincRNAs can also be targeted with HER2 to eliminate the tumor.
AACR, Author Interviews, Breast Cancer, NIH, Ovarian Cancer / 03.05.2015

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers. We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population.
Author Interviews, Breast Cancer, Genetic Research / 27.04.2015

Nasim Mavaddat M.B.B.S. MPhil PhD PhD  Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge, Cambridge, UKMedicalResearch.com Interview with: Nasim Mavaddat M.B.B.S. MPhil PhD PhD Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge, Cambridge, UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Mavaddat: Recent large-scale genome wide association analyses have led to the discovery of genetic variation- called single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Individually these variants confer risks that are too small to be useful for risk prediction. But when combined as a single score, called a polygenic risk score (PRS), this score may be used to stratify women according to their risk of developing breast cancer. This stratification could guide strategies for screening and prevention. Our study was a large international collaboration involving 41 research groups from many different countries and included 33,673 breast cancer patients and 33,381 controls. We found that the genetic variants act more or less independently, and that the more risk variants a woman has the higher her risk of breast cancer. When women were ranked according to their PRS, women with scores in the top 1% had a threefold increased risk of breast cancer. This translates into an absolute risk of breast cancer of 29% by age 80. By contrast, women with the lowest 1% scores had a risk of 3.5%. The PRS was effective in stratifying women with and without a family history of breast cancer, so that highest risk was for women with a family history and a high PRS. Finally, we showed that the PRS was better at predicting the risk of ER-positive breast cancer (potentially relevant to the application of risk stratification to chemoprevention for example, with tamoxifen, raloxifene or aromatase inhibitors). There has been much debate as to whether genomic profiles are useful for individual risk prediction, especially in the context of the preventative strategies available at the present time. The estimates provided in this study will help inform these debates.
AACR, Author Interviews, Breast Cancer, UCSD / 21.04.2015

Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New YorMedicalResearch.com Interview with: Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New York Medical Research: What is the background for this study? This year, breast cancer will claim the lives of nearly 40,000 women in the United States, and up to half of these women will have a disease that is driven by the estrogen receptor.
  • Although medicines have been approved for the treatment of hormone receptor-positive breast cancer for decades, more treatment options are needed.
  • Resistance to endocrine therapies causes morbidity and mortality for women with metastatic estrogen receptor-positive (ER+) breast cancer as many patients relapse or develop resistance to available hormonal agents via estrogen-dependent and estrogen-independent mechanisms.
  • Dual-acting investigational Selective Estrogen Receptor Degrader (SERDs) could potentially lead to a new treatment option for people with hormone receptor-positive breast cancer and may help overcome resistance to current anti-hormonal medicines.
  • GDC-0810 is a dual-acting investigational next-generation oral SERD that works in a number of ways to prevent estrogen fueling tumor growth. It is not only designed to target the estrogen receptor (ER) as an antagonist, but also to cause degradation of the ER protein. In preclinical studies, GDC-0810 was shown to induce tumor regressions in both tamoxifen sensitive and tamoxifen resistant tumor models in vivo.
Medical Research: What are the main findings?
  • Clinical data from the dose-escalation portion of a Phase I/IIa study evaluating GDC-0810 appears to have an acceptable safety profile with encouraging anti-tumor activity in postmenopausal women with advanced breast cancer positive for the estrogen receptor (ER), all of whom were previously treated with standard endocrine therapy.
  • Promising anti-tumor activity was observed in 38% of patients on study for six months or longer. At all doses tested, there was robust engagement of the estrogen receptor by GDC-0810 as demonstrated by fluoroestradiol (FES) PET scans.  Overall, the most common adverse events of any grade related to GDC-0810 were diarrhea, nausea and fatigue.
Author Interviews, Breast Cancer / 20.04.2015

Steven Jay Isakoff, MD, PhDHematology/Oncology Department of Medicine Massachusetts General HospitalMedicalResearch.com Interview with: Steven Jay Isakoff, MD, PhD Hematology/Oncology Department of Medicine Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Isakoff: Metastatic triple negative breast cancer remains a challenging clinical problem with no specific therapies targeted validated for this population.  From a number of preclinical studies and because of a link between BRCA1 associated breast cancer and triple negative breast cancer, platinum chemotherapy has emerged as a potential chemotherapy with activity in triple negative breast cancer.  However, it is not yet clear how to predict which triple negative breast cancer patients are more likely to respond to platinum chemotherapy.  We set out to answer several questions.
  • First, what is the response rate to platinum chemotherapy in the first or second line for metastatic triple negative breast cancer?
  • Second, can we identify biomarkers to predict response to platinum agents?  The results of our study showed that among 86 patients treated with platinum chemotherapy (either cisplatin or carboplatin), the response rate was about 25%.  We identified 11 BRCA mutation carriers in our population and the response rate among carriers was about 55% compared to about 20% in the non-carriers.  In addition, we found that a new assay called the Hologous Recombination Deficiency assay, which may identify tumors with a BRCA-like phenotype, seemed to predict which cancers were more likely to respond, whereas other biomarkers we looked at were not able to do so.
  • Another exciting finding was that 6 patients who had major responses have become long term responders with no subsequent progression, some whom for over 5 years so far.  Surprisingly, none of the long term responders are BRCA mutation carriers.
AACR, Author Interviews, Breast Cancer, Nutrition, UCSD / 20.04.2015

Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093MedicalResearch.com Interview with: Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093 MedicalResearch: What is the background for this study? What are the main findings? Response: The dietary advice for cancer prevention usually focuses on limiting consumption of red meat, alcohol, and refined grains, and increasing consumption of plant foods. However, new evidence suggests that other fundamental aspects of diet, such when and how often people eat, can also play a role in cancer risk. For example, research in mice suggests that decreasing the number of hours we eat during the day, and increasing the length of time we fast overnight can improve metabolic parameters and reduce risk of developing a number of chronic diseases including cancer. Similar to the data from animal models, we found that women who fasted for longer periods of time overnight had significantly better control over blood glucose concentrations – and these effects were independent of how much women ate. This finding is relevant to cancer research because people who have poor glucose control are significantly more likely to develop certain types of cancer. It is hypothesized that high concentrations of circulating glucose may fuel cancer growth and progression.
Author Interviews, Breast Cancer, Cancer Research, Cognitive Issues, JNCI / 19.04.2015

Dr. Kerstin Hermelink Senior psychologist  Dept. of Gynecology and Obstetrics Ludwig Maximilian University of MunichMedicalResearch.com Interview with: Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Munich MedicalResearch: What is the background for this study? What are the main findings? Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all. Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained. Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis. We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms. Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer.
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, University of Michigan / 06.04.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer.  Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations.
Breast Cancer, Health Care Systems / 06.04.2015

MedicalResearch.com Interview with: Dr. Karla Unger-Saldaña Unit of Epidemiology Instituto Nacional de Cancerología Mexico City, Mexico. Medical Research: What is the background for this study? Dr. Unger-Saldaña: Even though Breast Cancer is most common in the developed world, most cancer deaths actually occur in developing regions. This is mainly because patients are diagnosed in advanced stages, with poor chances of survival. Most studies have shown that long times between symptom discovery and treatment start (total delay) are associated with advanced clinical stage. Like total delay, patient delay -a prolonged time between symptom discovery and the first medical consultation- has also shown to be associated with advanced clinical stage. But the impact of health system delay -the time between the first clinical consultation and the start of cancer treatment- is less clear. Studies have shown contradictory findings. For example, studies in developed countries have found the reverse association: advanced stages associated with short times between first medical consultation and treatment start. This has been attributed to the ability of doctors to quickly identify patients with advanced cancer and somehow accelerate their care. Medical Research: What are the main findings? Dr. Unger-Saldaña: In this study, done among 886 patients, we found that the majority started cancer treatment in advanced stages, with only 15% being diagnosed in stages 0 and I. Also, we found long delays for breast cancer diagnosis and treatment in most cases. The median time between symptom discovery and cancer treatment start was 7 months. The longest subinterval was that between the first medical consultation and diagnosis confirmation, which had a median of 4 months. The most relevant result was that not only was patient delay associated with advanced stage, but also health system delay. For every additional month of health system delay, the probability of starting treatment in advanced stage was increased by 1%.
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 31.03.2015

Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, ChinaMedicalResearch.com Interview with: Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, China MedicalResearch: What is the background for this study? What are the main findings? Prof. Hu: Triple-negative breast cancer (TNBC) is associated with higher rates of recurrence, shorter disease free survival, and poorer overall survival. Molecular targeting agents tried against Triple-negative breast cancer have nearly all failed. TNBC, concordant with BRCA-associated and basal-like breast cancer, has abnormal DNA repair and genome-wide instability, supporting the use of DNA-damaging agents such as platinum. However, platinum monotherapy is not very potent, combination with other agents, such as gemcitabine has a synergistic effect. The GP regimen could be an alternative or even preferential first-line doublet chemotherapy strategy for patients with mTNBC.
Author Interviews, Breast Cancer, Depression, Mental Health Research / 23.03.2015

Michael H. Antoni, Ph.D. Professor of Psychology and Psychiatry and Behavioral Sciences Director, Center for Psycho-oncology Research Program co-Leader, Cancer Prevention Control and Survivorship Sylvester Cancer Center Sylvester Professor Director Miami CTSI Pilot and Translational Studies Component University of MiamiMedicalResearch.com Interview with: Michael H. Antoni, Ph.D. Professor of Psychology and Psychiatry and Behavioral Sciences Director, Center for Psycho-oncology Research Program co-Leader, Cancer Prevention Control and Survivorship Sylvester Cancer Center Sylvester Professor, Director Miami CTSI Pilot and Translational Studies Component University of Miami Medical Research: What is the background for this study? What are the main findings? Dr. Antoni: We have been conducting stress management intervention trials with breast cancer patients for the past two decades. We have shown that the form of stress management we developed, a 10-week cognitive behavioral stress management (CBSM) intervention, combining relaxation techniques, cognitive behavioral therapy techniques and coping and interpersonal skills training (assertiveness and anger management) delivered in a supportive group, can improve how women adapt during breast cancer treatment and up to one year later. These improvements in psychological status (less depressive symptoms, less negative mood and more positive mood) are associated with reductions in circulating serum cortisol levels, improved immune function and decreased inflammatory signaling over the first year of treatment. Since depressive symptoms are prevalent during cancer treatment our prior work showing that cognitive behavioral stress management reduces depressive symptoms over the 1st yr of treatment is significant . Since persisting depressive symptoms into survivorship are also common these new findings that women receiving cognitive behavioral stress management during primary treatment show beneficial effects out to 15 yrs suggests a real impact on their quality of life well into survivorship. Further, since data just released this week at the American Psychosomatic Society meeting in Savannah, GA shows that depressive symptoms during breast cancer treatment predict greater odds of mortality over the next 8-15 yrs it is plausible that these cognitive behavioral stress management effects on reduced long-term depressive symptoms may have implications for survival. Finally since depressive symptoms relate to greater signs of inflammation in breast cancer patients and because inflammation promotes cancer disease progression via effects on angiogenesis, invasion and metastasis, then managing depressive symptoms during and after active treatment for breast cancer could have effects on health outcomes via lower inflammation.
Author Interviews, Breast Cancer, JAMA / 18.03.2015

Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch: What is the background for this study? What are the main findings? Dr. Elmore: It is estimated that 1.6 million women in the United States each year undergo a breast biopsy. By interpreting these biopsies under the microscope, pathologists provide diagnoses on a spectrum from benign, to atypia, to ductal carcinoma in situ (DCIS), to invasive cancer. Using these diagnostic classifications, clinical doctors work with their patients to decide if they are at increased risk of developing breast cancer in the future, which can lead to additional surveillance, or how to treat them when the diagnosis is invasive breast cancer. As misclassification of breast lesions by pathologists may contribute to overtreatment and undertreatment of breast disease, we decided to study the accuracy of breast pathology diagnoses in the U.S. In the Breast Pathology (B-Path) Study, we used a set of 240 breast biopsy cases to evaluate the interpretive accuracy of 115 U.S. pathologists who were actively interpreting breast biopsies in their clinical practices. Their diagnoses were compared with reference diagnoses established by a consensus panel of experienced breast pathologists. When the panel members each independently diagnosed the slides pre-consensus, they agreed unanimously on 75 percent of their diagnoses; ninety percent of the panel members’ initial independent diagnoses agreed with the final consensus-derived reference diagnoses. When comparing participating pathologists’ diagnoses to the reference diagnoses, we found overall agreement for 75 percent of interpretations. The concordance rate for invasive breast cancer was reassuringly high at 96 percent, and fairly high for benign findings without atypia at 87 percent. However, concordance was lower for atypia at 48 percent and for DCIS at 84 percent. This means that nearly one out of five pathologists disagreed on the diagnosis of DCIS. We found disagreement with the reference diagnosis to be statistically more frequent when pathologists had lower weekly case volumes or worked in smaller labs. Disagreement was also statistically significantly more likely when the patient had dense breast tissue on mammogram; however, the absolute difference was small. Our accuracy findings were not altered when we used different methods of defining the reference diagnosis.
Author Interviews, Breast Cancer, NEJM / 10.03.2015

Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI MedicalResearch.com Interview with: Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI Medical Research: What is the background for this study? What are the main findings? Dr. Pugh: The clinical breast examination is routinely performed on millions of women each year. It is used for screening breast cancer and is also routinely performed on women presenting with symptomatic breast conditions. In this study we assessed the performance of the clinical breast examination among a large sample of practicing physicians. There were two main goals to the study. The first goal was to identify current recommendations for performing the clinical breast examination and investigating how this relates to examination sensitivity or finding a mass. The second and more general goal was to develop a method for objective assessment of clinical skills. Novel clinical breast examination simulators were used in this study; in addition to their ability to present different pathologies and multiple clinical scenarios, they were all integrated with advanced force sensors. These sensors include approximately 2000 discrete sensing elements, measuring force level and distribution thought the breast examination. These sensors provide information at a level of detail that is not possible with observation alone. Four models were used in this study; two models presenting superficial soft masses and two models representing hard chest wall masses. The study was performed from 2013 to 2014 with 553 physicians performing the clinical breast examination on our models. The participants were recruited at three annual clinical meetings: 136 at the American Society of Breast Surgeons, 236 at the American Academy of Family Physicians, and 181 at the American College of Obstetricians and Gynecologists. The study found a significant relationship between the force used during palpation and the accuracy of the assessment of the deep-tissue lesions. More specifically, the study found that some physicians don’t apply enough force during the examination putting them at high risk of missing deep-tissue lesions. Since force can’t be measured by human observation this underscores the added value of integrating sensors into clinical simulators.
Author Interviews, Breast Cancer, NIH / 08.03.2015

Dr. Clarice R. Weinberg Ph.D Biostatistics and Computational Biology Branch National Institute of Environmental Health Sciences Research Triangle Park, NC 27709Medicalresearch.com Interview with: Dr. Clarice R. Weinberg Ph.D Biostatistics and Computational Biology Branch National Institute of Environmental Health Sciences Research Triangle Park, NC 27709 MedicalResearch: What is the background for this study? Dr. Weinberg: Hormone therapy (HT) was commonly prescribed in the U.S. late in the 20th century to help women through the challenges of menopause. Several decades ago, therapy with estrogen alone was shown to cause endometrial cancer, and the combined use of both estrogen and progesterone replaced treatment with estrogen alone. But research published around 2002 had far reaching effects on gynecologic practice. Both the randomized trial component of the US Women’s Health Initiative and the observational European Million Women’s Study reported that postmenopausal women who were older than 50 and were taking the combination HT had an increased risk of breast cancer. Physicians and patients responded quickly, and Hormone therapy use plummeted. However, it remained unclear whether there were risks of Hormone therapy use in women under age 50. Some factors, for example obesity, have opposite effects on the risk of breast cancer in pre- and post-menopausal women, so one cannot assume risk findings from older women necessarily apply to younger women. We carried out a sibling-based study of 1,419 women with breast cancer diagnosed under the age of 50 (http://sisterstudy.niehs.nih.gov/English/2sis.htm). Each case had a sister (also studied) who had never been diagnosed with breast cancer, who could serve as her control. The study was funded by Susan G. Komen for the Cure, and the National Institutes of Health.
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA, Personalized Medicine / 05.03.2015

Dr. Michaela A. Dinan Ph.D Department of Medicine Duke UniversityMedicalResearch.com Interview with: Dr. Michaela A. Dinan Ph.D Department of Medicine Duke University Medical Research: What is the background for this study? What are the main findings? Dr. Dinan: We wanted to examine how  Oncotype DX® Breast Cancer Test (ODX) was being used in real-world practice at the population level. ODX has been examined in clinical trials and limited academic settings but we know that these patients are often younger, have fewer medical comorbidities, and do not necessarily accurately reflect the majority patients with cancer.  In our study, we observed that Oncotype DX® Breast Cancer Test was being used predominately in accordance with guidelines which recommend the test for women with estrogen-receptor positive, node negative disease. We also looked just at women under the age of 70 who met guideline criteria for testing, because this population would include those women who were more likely to be chemotherapy candidates, and we saw a rapid uptake of the test between 2005 and 2009, with use of the test increasing from 8% to 39%.
Author Interviews, Breast Cancer, Chemotherapy, Cleveland Clinic, NEJM / 04.03.2015

Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195MedicalResearch.com Interview with: Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Moore: Ovarian failure is a common long-term side effect of chemotherapy. Previous studies investigating whether suppressing ovarian function during chemotherapy treatment will preserve ovarian function following chemotherapy have had mixed results. Our study found that suppressing the ovaries with the GnRH analog goserelin during chemotherapy treatment for early stage ER-negative breast cancer resulted in a reduced risk of ovarian failure two years after initiation of treatment. Also, more women who received the goserelin with chemotherapy became pregnant than women who received chemotherapy without goserelin. In addition, there was an apparent improvement in survival among the goserelin group, confirming the safety of this approach in this patient population.
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2015

MedicalResearch.com Interview with: Dr. Lucia Del Mastro MD Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genova, Italy Medical Research: What is the background for this study? What are the main findings? Response: Adjuvant chemotherapy regimens with anthracyclines and taxanes improve the outcome of patients with early breast cancer. Among the most widely used anthracycline-based chemotherapy in sequential combinations with the taxane paclitaxel (P) there are epirubicin and cyclophosphamide (EC) and fluorouracil, epirubicin, and cyclophosphamide (FEC). The contribution of fluorouracil to the anthracycline-cyclophosphamide regimen (EC) was unclear until now. Various randomized trials attempted to assess the role of a more intense schedule of chemotherapy (i.e. dose-dense chemotherapy with cycles administered every 2 weeks instead of every 3 weeks) in patients with early breast cancer. However, most of these trials compared dose-dense chemotherapy with regimens that use standard intervals but with different drugs or dose in the treatment groups, thus making difficult to extrapolate the true role of the dose-dense strategy. The results of GIM2 study show that the addition of fluorouracil to  a sequential regimen with epirubicin, cyclophosphamide and paclitaxel increases the toxicity, in terms of neutropenia, fever, nausea, and vomiting, and is not associated with an improved outcome compared with the same treatment without fluorouracil.
Author Interviews, Breast Cancer, NEJM / 19.02.2015

  Swain_SandraMedicalResearch.com Interview with: Sandra M Swain, MD, FACP, FASCO Medical Director, Washington Cancer Institute MedStar Washington Hospital Center Washington DC 20010 MedicalResearch: What take-home message would you like the general public to understand about this new analysis from the Cleopatra study? Potential Key Message Options:
  • Updated results from the CLEOPATRA study showed that people treated with the combination of pertuzumab, trastuzumb and chemotherapy lived 15.7 months longer than those who received trastuzumab and chemotherapy alone (median survival of 56.5 months versus 40.8 months).
  • The survival improvement of nearly 16 months observed in CLEOPATRA is unprecedented among studies of metastatic breast cancer. This is the kind of survival improvement that those of us who treat breast cancer strive for, and this data will be incredibly meaningful to patients and their families.
  • Furthermore, the median survival of nearly five years observed in CLEOPATRA patients treated with the pertuzumab regimen is the longest ever observed in a clinical study of people with HER2-positive metastatic breast cancer, once one of the most aggressive forms of breast cancer.
  • Patients who responded with shrinkage of their tumor had a response that was 8 months longer with the pertuzumab regimen compared to the trastuzumab and chemotherapy regimen.
Author Interviews, Breast Cancer / 11.02.2015

Alejandra Valenzuela-IglesiasMedicalResearch.com Interview with: Alejandra Valenzuela-Iglesias Ph.D. candidate Department of Molecular Biology University of Sonora Hermosillo, Sonora MedicalResearch: What is the background for this study? What are the main findings? Response: Breast cancer is one of the leading causes of cancer death in women all around the world. In recent years, there has been great interest in creating new therapies that will help to prevent or stop metastasis, but the therapies developed up until today are not completely effective. Metastasis is the main cause of death for a cancer patient because it implies that tumor cells have detached from the primary tumor and have colonized in one or more vital organs or tissues in the organism. For this to occur, the invasive tumor cells form actin-driven membrane protrusions called invadopodia. These protrusions possess proteolytic activity to degrade the basal membrane and extracellular matrix, which facilitates metastatic cancer cells to enter the bloodstream and spread to distant organs in the body. It has been shown that any dysregulation in the actin cytoskeleton leads to impaired invadopodia formation. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas. Our study was a collaboration between Albert Einstein College of Medicine, University of Pittsburgh, and University of Sonora, lead by Dr. Jose Javier Bravo-Cordero and published in the European Journal of Cell Biology. We showed for the first time the role of profilin1 in invadopodia formation and function in human breast cancer cells MDA-MB-231. By using cell imaging techniques we unveiled the dynamic of the profilin1-depleted cells, finding that profilin1 can act as a negative regulator of breast cancer cell invasion, acting as a break in invadopodia turnover, by modulating the molecules involved in invadopodia maturation. The removal of profilin1 expression accelerates invadopodia maturation rate, explaining the invasive phenotype previously reported for this type of cells.
Author Interviews, Baylor College of Medicine Houston, Breast Cancer / 10.02.2015

Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, TexasMedicalResearch.com Interview with: Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, Texas   Medical Research: What is the background for this study? What are the main findings? Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they  the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process. In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones. We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases.