MedicalResearch.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.
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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.
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MedicalResearch.com Interview with:
Bernadette A.M. Heemskerk-Gerritsen, Ph.D.
Department of Medical Oncology
Erasmus MC Cancer Institute
Roterdam, the NetherlandsMedical 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.
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MedicalResearch.com Interview with:
Ahmad M. Khalil, PhD
Assistant professor, Department of Genetics and Genome Sciences
Case Western Reserve University School of Medicine
MedicalResearch: What is the background for this study? What are the main findings?Dr. Khalil: This study aimed to identify other genes that work synergistically with the oncogene HER2 in HER2positive (HER+) breast cancer. The gene HER2 is amplified in those patients, which results in excess activities that promote uncontrolled cell growth. There are drugs that target HER2 and diminish its activity. However, these drugs can work initially, but patients relapse; or sometimes, the drugs don't work at all in some patients.
Thus, by identifying other genes that work synergistically with the HER2 gene, we now have more genes to target by various drugs or compounds to destroy the tumor. The challenge was how to identify the key genes that work synergistically with HER2, especially in human subjects. To that end, we used clinical samples from a clinical trial of a drug that is known to inhibit HER2 activity to identify those genes. To further refine our list, we used cell culture models of the disease to also inhibit HER2. By combining those data sets, we identified 44 protein-coding genes.
Next, we wanted to make sure that those genes stand a third independent filter. For that part, we interrogated those 44 genes in HER2+ tumors vs matched normal tissues from The Cancer Genome Atlas database — a collection of hundreds of tumors and normal tissues. Of the 44 genes, 35 genes passed this third filter. By examining the known functions of those genes, we can deduce that those genes work cooperatively with HER2 to promote carcinogenesis.
There are currently known drugs that target some of those genes. We will use these drugs in combination with a drug that target HER2 to determine if the combination works better at destroying the tumor entirely.
Lastly, we found that a special type of genes that we previously discovered, called lincRNAs, could also affect the oncogenic activity of HER2. These lincRNAs can also be targeted with HER2 to eliminate the tumor. (more…)
MedicalResearch.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.
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MedicalResearch.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.
MedicalResearch.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.(more…)
MedicalResearch.com Interview with:
Cary P. Gross MD
Professor of General Medicine, of Epidemiology (Chronic Diseases) and of Faculty of Arts and Sciences
Yale...
MedicalResearch.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.
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MedicalResearch.com Interview with:
Dr. Karla Unger-SaldañaUnit 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%.
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MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.com Interview with:
Danil Makarov, MD Lead Investigator
Assistant Professor, Departments of Urology, Population Health and Health Policy
Member, Laura and Isaac Perlmutter Cancer Center
NYU Langone Medical Center, New York, NY
Medical Research: What is the background for this study?
Dr. Makarov: The background for this study is that regional variation in patterns of care and healthcare spending is widely known. The drivers of this regional variation, though, are poorly understood. Certain policy groups like the IOM have suggested that policy efforts be focused on individual providers and patients. Programs such as Choosing Wisely, which encourage a dialogue between physicians and patients, are a great example of such efforts. However, some of our prior research suggests that regional variation is not random and that there might be are regional-level factors which drive variation.
To test out our hypothesis, we wanted to see whether inappropriate imaging for two unrelated cancers was associated at a regional level (it should not be).
Medical Research: What are the main findings?
Dr. Makarov: We found that, at a regional level, inappropriate breast cancer imaging was associated with inappropriate prostate cancer imaging.
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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. (more…)
Medicalresearch.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.
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MedicalResearch.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, 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%.
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MedicalResearch.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.
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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. (more…)
MedicalResearch.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.
MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.com Interview with:
Dr. Amy C. Degnim MD
Professor of Surgery
Mayo Clinic, Rochester.
Medical Research: What is the background for this study? What are the main findings?
Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future. We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model). We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT).
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MedicalResearch.com Interview with:
William J. Brackenbury, Ph.D.
MRC Fellow Department of Biology
University of York, Heslington, York UK
Medical Research: What is the background for this study?Dr. Brackenbury: Metastasis, the spread of cancer cells from the primary tumour to secondary sites, e.g. the lungs or bones, is the main cause of deaths from cancer. However, there are no effective treatments available to slow or stop this devastating aspect of the disease. We and others have found that sodium channels, normally present in neurons and muscle cells, are up-regulated in metastatic breast cancer cells. Sodium channels appear to regulate the behaviour of these cancer cells, helping them to move and squeeze their way out of the primary tumour as they invade and metastasise on their way to distant sites. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis.
Medical Research: What are the main findings?
Dr. Brackenbury: Sodium channels are important drug targets for treating epilepsy. We have found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduces tumour growth and metastasis in a preclinical model of breast cancer. We found that phenytoin reduces proliferation of cancer cells within the primary tumour. It also reduces local invasion of cancer cells into the surrounding fat and muscle, and reduces the number of cells metastasising to distant sites in the liver, lungs and spleen. (more…)
MedicalResearch.com Interview with:
Rachel A. Freedman MD, MPH
Assistant Professor of Medicine, Harvard Medical SchoolDepartment of Medical Oncology
Dana-Farber Cancer Institute, Boston, MassachusettsMedical Research: What is the background for this study? What are the main findings?Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases. (more…)
MedicalResearch.com Interview with:
Dr Jingmei Li
Department of Medical Epidemiology and Biostatistics
Karolinska Institutet Stockholm, SwedenMedical Research: What is the background for this study? What are the main findings?
Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes.
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MedicalResearch.com Interview with:
Cecilia Cesa Schiavon
Department of Nutrition, Federal University of Santa Catarina
Florianópolis, Santa Catarina, Brazil
Medical Research: What is the background for this study? What are the main findings?
Response: The study was based on a nutritional intervention for patients undergoing treatment for breast cancer. The intervention took place right after the surgical procedure and lasted about a year, until the end of chemotherapy. The patients were submitted to a special methodology of intervention, aimed at increasing fruit and vegetable intake and reducing red and processed meat, following the World Cancer Research Fund and the American Institute for Cancer Research in the document entitled Food, Nutrition, Physical Activity and the prevention of Cancer: A Global Perspective”.
The main findings show that women undergoing breast cancer treatment may benefit from immediate, individualized, and detailed nutrition monitoring through appropriate nutrition education.
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MedicalResearch.com Interview with:
Dr. Jorge Morales-Montor
Departamento de Inmunología
Instituto de Investigaciones Biomédicas
Universidad Nacional Autónoma de México
México City México
MedicalResearch:What is the background for this study?Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders.
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MedicalResearch.com Interview with:
Javaid Iqbal, MD, MSC (Candidate)
Institute of Medical Sciences, and
Women’s College Research Institute/Women’s College Hospital
University of Toronto, Toronto Canada
What is the background for this study? What are the main findings?Dr. Iqbal: A woman’s racial/ethnic background predicts her participation in breast cancer control program (i.e., awareness and screening). The ultimate objective of breast cancer control program is to detect cancer at an optimal stage, which is stage I, because women with stage I breast cancer survive longer. Given the racial/ethnic diversity of North America, this poses questions such as “what predicts stage I breast cancer in the multiethnic North American population?”, “what predicts its survival?”, and “does a woman’s ethnic background plays a role in predicting an early stage, and survival?”
We studied 373,563 women diagnosed with invasive breast cancer in the United States between 2004 and 2011. We followed these women for 7 years and recorded whether or not they died of breast cancer, or whether they are still alive. We then divided all women into different ethnic groups, in particular white, black, Chinese, Japanese, and Indian/Pakistani (South Asian). For each racial/ethnic group, we estimated proportions of women who were diagnosed with stage I breast cancer, and risk of death at 7 years. Our aim was to determine if the racial/ethnic differences in early stage breast cancer, and its survival were better explained by intrinsic biological differences in tumor characteristics, or by differences in early-detection of breast cancer.
We found that a woman’s racial/ethnic background predicted the diagnosis of stage I breast cancer, as well as her risk of dying at 7 years after breast cancer. A black woman was less likely than a white woman to be diagnosed with stage I breast cancer. A black woman was also more likely than a white woman to die of stage I breast cancer 7 years after her diagnosis. The Japanese and Chinese women were more likely than white women to be diagnosed with stage I breast cancer. The risk of death at 7 years was lowest for Indian or Pakistani (South Asian) women. Furthermore, even for small sized (2.0) breast cancers the risk of death at 7 years was higher for black women (9%), compared to white women (5%). Compared to white women, small sized breast cancers in black women were more aggressive at diagnosis, and had spread to lymph nodes and other organs.
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MedicalResearch.com Interview with:
Dr. Pentao Liu PhD and Dr. Walid Khaled PhD
Wellcome Trust Sanger InstituteCambridgeshire United Kingdom
Medical Research: What is the background for this study? What are the main findings?
Dr. Pentao Liu: The significance of this research is that it aims to tackle the worst type of breast cancer. Triple Negative Breast Cancer (TNBC) has the poorest patient survival rate compared to other forms of breast cancer. At present there are no targeted therapies available for TNBC, leaving the non-specific chemotherapy as the only treatment option. In this study we identify a new key gene in Triple Negative Breast Cancer which could potentially be inhibited for the targeted treatment of TNBC.
In this study we report the identification of a novel gene for Triple Negative Breast Cancer. By analyzing genomics data from 3,000 patients we find BCL11A to be highly expressed in TNBC. We then demonstrate experimentally that upregulation of BCL11A drives tumour development while its downregulation leads to reduction in tumour size. In the experimental mouse model, inactivation of this gene completely abolishes breast tumour development.
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MedicalResearch.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.
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