MedicalResearch.com Interview with:
Dr. Alexandra White PhD in Epidemiology
University of North Carolina at Chapel Hill
Postdoctoral fellow
National Institute of Environmental Health Science
MedicalResearch: What is the background for this study? Dr. White: Many studies have shown that being overweight or obese is a risk factor for postmenopausal breast cancer. We know less about how obesity impacts breast cancer risk in premenopausal women.
About a third of U.S. adults are obese, which is defined as having a body mass index (BMI) greater than 30. Similarly, the prevalence of abdominal obesity, measured by a person’s waist circumference, has increased by 10% in the last decade. In 2012, more than two-thirds of U.S. women had a waist circumference that indicated abdominal obesity.
Abdominal obesity may be a better predictor than BMI for breast cancer risk and other chronic diseases, because it is related to insulin resistance and can reflect metabolically active fat stores.
In order to understand how different types of obesity (overall vs. abdominal) influence breast cancer risk, we used information from >50,000 participants in the Sister Study. The Sister Study, led by scientists at the National Institute of Environmental Health Sciences, part of the National Institutes of Health investigates environmental and genetic risk factors for breast cancer.
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MedicalResearch.com Interview with:
Michaela Ann Dinan Ph.D.
Assistant Professor in Medicine
Member of Duke Cancer Institute
Duke University School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Dinan: For many years we have known that overall, women with early stage, hormone receptor positive breast cancer show an overall survival benefit from the receipt of adjuvant chemotherapy. However, depending on the age of the patient, we have also known that between 3 to 10% of patients appear to be truly experiencing this survival benefit and that we are treating a lot of women unnecessarily. The use of the Oncotype DX assay has provided additional information for patients to assess who at low risk of disease progression and can forgo chemotherapy.
In this study we looked to see whether the adoption of this assay was associated with reduce rates of chemotherapy in women over the age of 65. We found that somewhat surprisingly, there was no overall association with receipt of the assay and use of chemotherapy. However, in women who had high risk disease, receipt of the assay was associated with reduced rates of chemotherapy use. In patients with low risk disease, receipt of the assay was associated with increased chemotherapy use.(more…)
MedicalResearch.com Interview with:
Tuya Pal MD
Division of Population Sciences
Department of Health Outcomes and Behavior
Moffitt Cancer Center
Tampa, Florida
Medical Research: What is the background for this study?
Dr. Pal: Young Black women bear a disproportionate burden associated with breast cancer incidence and mortality compared to their White counterparts. Given that inherited mutations in the BRCA1 and BRCA2 genes are more common among young breast cancer survivors, we questioned to what extent mutations in these genes might contribute to the racial disparity in breast cancer incidence among young women.
Medical Research: What are the main findings?
Dr. Pal: Through conducting the largest U.S. based study of BRCA mutation frequency in young black women diagnosed with breast cancer at or below age 50, we discovered they have a much higher BRCA mutation frequency than that previously reported among young white women with breast cancer. Specifically, of the 396 Black women with breast cancer diagnosed at or below age 50, 12.4% had mutations in either BRCA1 or BRCA2. Furthermore, over 40 percent of those with a mutation had no close relatives with breast or ovarian cancer, which suggests that family history alone may not identify those at risk for carrying a BRCA mutation.(more…)
MedicalResearch.com Interview with:
Jaclyn Bradley Palmer, MM, MT-BC
University Hospitals Of Cleveland
Cleveland, OH
Medical Research: What is the background for this study? What are the main findings?
Response: Patients awaiting breast cancer surgery may be understandably anxious. While pharmacologic intervention may reduce anxiety, higher doses of preoperative drugs can depress circulation and respiration, making alternative measures a particular interest. Music therapy is the clinical use of music interventions to accomplish individualized goals within a therapeutic relationship by a board-certified music therapist. While music in surgery has been researched under the label of "music therapy", many of the studied investigations illicit recorded music provided by non-music therapy staff, making it truly "music medicine" practices instead. In this investigation, the effect of both live and recorded music therapy on anxiety, anesthesia requirements, recovery time and patient satisfaction were studied perioperatively. Breast cancer surgery patients were engaged in a brief music therapy session which consisted of one live or recorded preferred song choice, followed by discussion and processing of emotions. Compared to usual care, both live and recorded music therapy groups experienced significantly greater reductions in anxiety (p<.001) with point reductions of 27.5 (42.5%) and 26.7 (41.2%), respectively. During surgery, both music groups listened to music-therapist selected recorded, instrumental harp music, chosen for it's evidence-based therapeutic value of smooth lines, consistent volumes and stable melodies. In measuring the amount of interoperative drug (propofol) needed to reach moderate sedation, the intraoperative music was not found to have an effect in this trial. Patient satisfaction was universally high in all three study groups. Those who received live music preoperatively were discharged an average of 12.5 minutes sooner than those who received recorded music preoperatively, although neither music group was dischanged significantly sooner than the control group. Subjective reactions to the music interventions relayed that music therapy in surgery was an enjoyable addition.
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MedicalResearch.com Interview with:
Philip M.P. Poortmans PhD MD
Head of Department, Radiation Oncology
ESTRO President
Radboud university medical center
The Netherlands
Medical Research: What is the background for this study?
Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.
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MedicalResearch.com Interview with:
Leif W. Ellisen, M.D., Ph.D
Professor of Medicine, Harvard Medical School
Program Director, Breast Medical Oncology
Co-Leader, Breast Cancer Program
MGH Research Scholar MGH Cancer Center
Boston, MA 02114
Medical Research: What is the background for this study? What are the main findings?
Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific.
Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families. Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family.
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MedicalResearch.com Interview with: Dr Stephen Chan DM, FRCR, FRCP
Consultant Oncologist Breast and Gynaecological Cancers
Nottingham University Hospitals Trust
Honorary Professor at the University of Nottingham
Visiting Professor of Cancer Medicine at Nottingham Trent University
MedicalResearch: What is the background for this study? What are the main findings?Dr. Chan: Worldwide each year 1.68 million women are diagnosed with breast cancer and more than half a million die from the disease. Of these new cases around 12% will be classified as triple negative breast cancer (TNBC), meaning that tumour cells from these patients do not show any of the three established clinical markers that can be treated with targeted therapies. These drugs are used in addition to standard chemotherapy to improve the chance of a good treatment response, leading to prolonged disease free survival. Without these additional treatment options triple negative patients are forced to depend entirely on chemotherapy to treat their cancer.
Traditionally the sensitivity of a cancer to different types of chemotherapy has been categorised is based on a tumours tissue of origin and stage. There is currently no predictive marker of response that would allow chemotherapy treatment to be tailored to individual patients. With this information a clinician can predict which patients would benefit most from a particular chemotherapy and switch any who would do poorly to an alternative. The result would be a shift to increased treatment efficacy, while avoiding toxicity from ineffective treatment, which would in turn also reduce the cost to the health service. This need is particularly acute in triple negative breast cancer cases where chemotherapy is the cornerstone of treatment.
In collaboration with researchers based at Nottingham Trent University our group has been successful in finding new markers, which can predict how a patient will respond to chemotherapy treatment. One of these is HAGE (DDX43), a DEAD box RNA helicase. We have found that high HAGE expression predicts good respond to one of the main first line chemotherapy drugs, called anthracycline (Tarek MA Abdel-Fatah et al, April 2014). Our recent work (Tarek MA Abdel-Fatah, 2015) has shown that the predictive value is strong in triple negative breast cancer cases.
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MedicalResearch.com Interview with:
Simona F. Shaitelman, MD, EdM
Assistant Professor
Department of Radiation Oncology
University of Texas MD Anderson Cancer Center
Houston, TX 77030
Medical Research:...
MedicalResearch.com Interview with:
Karla M. Gonye, MBA
President, sphingotec LLC
Cambridge, Massachusetts
MedicalResearch: What is the background for this study?
Response:
Met- and Leu-Enkephalin: are endogenous pentapeptides of the family of opioid peptides known as opiod-growth factors (OGF)
Enkephalins have been widely studied and play a major role in a variety of physiological processes
Perception of pain
Regulation of stress
Regulation of cardiovascular function
Regulation of bone formation
Regulation of immune responses
Alcohol and pain relievers reduce synthesis of Enkephalins
Met-Enkephalin (opioid growth factor) inhibits tumor progression and metastasis and enhances natural killer cell activity1,2
Mechanisms3-7:
Opioids can directly interact with tumor cells to cause a cytotoxic or antiproliferative effect
Opioids can modulate host antitumor immune mechanisms
Opiods can also induce apoptosis
We need enkephalins to help inhibit tumor progression
At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that reduced enkephalins in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure enkephalin.
This method is published in a separate publication by Ernst et al (2006) in Peptides.
To test this hypothesis, Sphingotec measured enkephalin levels in the MDC and MPP study populations to determine if an association could be made between lower enkephalins and risk of breast cancer: We related proenkephalin (P-ENK) in fasting plasma from 1929 healthy women (mean age 58±5.9 years) of the population based Malmö Diet and Cancer Study (MDCS) to incidence of breast cancer (n=123) using multivariate Cox proportional hazards models during 14.8 years of follow-up. For replication, P-ENK was related to risk of breast cancer (n=130) in an older independent sample from the Malmö Preventive Project (MPP) consisting of 1569 women (mean age 70.0±4.4 years), using multivariate logistic regression.
MedicalResearch.com Interview with:
Karla M. Gonye, MBA
President, Sphingotec LLC
Cambridge, Massachusetts
MedicalResearch: What is the background for this study?
Response:
In experimental studies, Neurotensin and neurotensin expression was highly associated to breast cancer tissue
Dupouy et al (2009) investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal carcinomas (IDCs) and found that NTS is expressed in ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade 3 (p<0.05), larger tumor size (p<0.01), and the number of metastatic lymph nodes (p<0.05).
It was concluded from this paper that NTS/NTSR1 is a contributor to breast cancer progression.
Souaze et al (2006)also studied IDCs and found 34% of all tumors were positive for neurotensin and 91% positive for the NT1 receptor, suggesting the contribution of neurotensin’s involvement in the signaling cascade within breast cancer progression. In this study, it was found that disruption of neurotensin receptor signaling by silencing RNA or using a specific NT1 antagonist in nude mice xenografted with an aggressive cell line SR48692, caused the reversion of transforming functions that lead to tumor growth.
These findings support the contribution of neurotensin to breast cancer progression.
Wu, Z. et al (2013) reviewed the contribution of the neurotensinergic system to cancer progression, as well as the regulation and mechanisms of the system in order to highlight its potential as a therapeutic target, and its prospect for its use as a treatment in certain cancers.
This summarizes nicely the oncogenic effects of neurotensin after stimulation signaling proliferation, survival, migration, invasion and neoangeogeneis.
Several other papers published demonstrate the effects of neurotensin in cancers including breast cancer.
New studies such as Roselli et al (2015) further demonstrate the role of neurotensin in aggressive breast cancer.
At sphingotec, it was hypothesized that disease progression begins earlier than symptoms are present and that elevated expression of neurotensin in the blood would be an indicator of future breast cancer; measurement of this hormone peptide was possible with the company’s expertise, and that test could be developed to precisely measure neurotensin.
This method is published in Ernst et al (2006) in Peptides.
To test the hypothesis, the first clinical study was conducted in a cohort of normal healthy population that was indentified from the Malmo Diet and Cancer study, a prospective epidemiological study of 28,449 men and women. Of this group, a subset of 4632 randomly selected subjects were identified and neurotensin was measured in all subjects. Subjects were adjusted for known breast cancer risk factors such as age, age of menarche, heredity of cancer (all), hormone status, etc. (see Table 3, Melander et al JAMA 2012) so that the factors did not influence outcomes. On a 10-15 follow up period, of these subjects, 123 breast cancer events were found to be associated with higher levels of neurotensin, with the highest quartile associated with the highest levels of neurotensin and the lowest quartile associated with the lowest levels of neurotensin. The association of elevated neurotensin was found to be statistically significant for prediction of breast cancer.
MedicalResearch.com Interview with:
Martha F. Goetsch, MD, MPH
Oregon Health & Science University
Portland, OR 97239
MedicalResearch: What is the background for this study?Dr. Goetsch: Women who are survivors of breast cancer now number about 3 million in the US. Therapy for breast cancer is anchored in creating a state of postmenopause in which estrogen is eliminated from the system. One of the most difficult symptoms of lack of estrogen is dyspareunia, the term for pain with intercourse. The old term “vulvovaginal atrophy” has been changed to “genitourinary syndrome of menopause” by agreement of two specialty societies. Because of my focus in the gynecologic specialty of vulvar pain, I have felt that this menopausal symptom is more than a condition of atrophy. Additionally, my clinical experience has led me to believe that the exquisite tenderness is located in the vulvar vestibule rather than in the vagina. The vestibule is the inner vulva or entryway before the vagina. This study was devised to answer these hypotheses.
I predicted that the population most likely to represent the worst examples of postmenopausal dyspareunia was the population of women who cannot use estrogen due to being survivors of breast cancer. I treated the problem as a pain problem rather than solely a problem of dryness.
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MedicalResearch.com Interview with:
Mitchell H. Gail, M.D., Ph.D.
Senior Investigator
Biostatistics Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute National Institutes of Health
Rockville MD 20850-9780
Medical Research: What is the background for this study?
Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the trends in age- and stage-specific breast cancer death rates after diagnosis.
We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ. We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant).
Medical Research: What are the main findings?
Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter. For women under age 70, rates also fell for women with distant disease.
Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis. (more…)
MedicalResearch.com Interview with:
Helmneh Sineshaw, MD, MPH
Senior Epidemiologist, Health Services Researcher
American Cancer Society, Inc
Atlanta, GA 30303
MedicalResearch: What is the background for this study? Dr. Sineshaw: Male breast cancer is a rare disease, and its incidence rate is increasing. Younger black men have a higher breast cancer incidence than their white counterparts. Although black/white disparities in treatment receipt and survival among women with breast cancer have been widely documented in the literature, there have been few similar studies in men with breast cancer. Previous studies were based on smaller sample size, older databases, or using data from elderly patients.
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MedicalResearch.com Interview with:
Alison L. Chetlen, D.O.
Associate Professor, Department of Radiology
Penn State Milton S. Hershey Medical Center
Hershey, PA 17033
Medical Research: What is the background for this study?
Dr. Chetlen: Breast cancer risk assessment provides a means of identifying women who are at risk for development of this disease. Identifying individuals at high risk for breast cancer allows for genetic testing, supplemental breast cancer screening, possibly prophylactic surgery or chemoprevention in hopes of decreasing mortality from breast cancer. Despite the advantages of cancer genetic risk assessment and testing, most individuals in the general population who would benefit from such services currently do not receive them.
Medical Research: What are the main findings?
Dr. Chetlen: After implementation of a specific high-risk recommendation within our standardized mammography report along with a letter written in “lay” language informing patients of their high-risk status, the number of referrals to our high-risk clinic increased only modestly. Despite these specific recommendations to both physicians and patients, over 85% of high risk patients did not consult a high-risk provider regarding their elevated lifetime risk of breast cancer.
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MedicalResearch.com Interview with: Niels de Jonge, Ph.D
Head of the Innovative Electron Microscopy group
German Cancer Research Center (DKFZ) in Heidelberg
University of Freiburg
Medical Research: What is the background for this study? What are the main findings?
Response: HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood. We now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth.
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MedicalResearch.com Interview with:
Dr. Vincent L. Cryns MD
Chief of the Division of Endocrinology, Diabetes and Metabolism
Department of Medicine
University of Wisconsin Carbone Cancer Center
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin
Medical Research: What is the background for this study? What are the main findings?Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or die. What’s been missing is a molecular explanation for these effects that would allow us incorporate this approach into a rationally designed clinical trial. In our work, we have demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a “fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a targeted cancer therapy. (more…)
MedicalResearch.com Interview with:
Dr. Jürg Bernhard Ph.D.
International Breast Cancer Study Group Coordinating Center and Bern University Hospital, Inselspital, Bern, Switzerland
Medical Research: What is the background for this study? What are the main findings?
Response: In the combined analysis of the SOFT and TEXT trials, the aromatase inhibitor exemestane was more effective than tamoxifen in preventing breast cancer recurrence in young women (premenopausal) who also receive ovarian function suppression (OFS) as adjuvant (post-surgery) treatment for hormone-sensitive early breast cancer, providing a new treatment option for these women. These trials were conducted by the International Breast Cancer Study Group (IBCSG) and involved more than 4700 patients of over 500 centers in 27 countries. Now we present patient-reported quality of life outcomes from these trials.
In the TEXT and SOFT trials, patients assigned exemestane+OFS reported more detrimental effects of bone or joint pain, vaginal dryness, greater loss of sexual interest and difficulties becoming aroused, while patients assigned tamoxifen+OFS were more affected by hot flushes and sweats. Global quality of life domains (mood, ability to cope and physical well-being) were similar between the randomized treatment groups. (more…)
MedicalResearch.com Interview with:
Dr. Mitchell Kamrava MDDepartment of Radiation Oncology
University of California Los Angeles
Los Angeles, CA
Medical Research: What is the background for this study? What are the main findings?
Dr. Kamrava: Breast conservation (lumpectomy followed by radiation) is known, based on multiple randomized trials with over 20 years of follow-up, to provided equivalent outcomes as mastectomy. The radiation component of breast conservation has standardly been delivered to the whole breast. Studies show that the majority of breast recurrences occur near the lumpectomy cavity causing some to ask whether it is necessary to treat the whole breast in order to reduce the risk of a recurrence.
Partial breast radiation delivers treatment just to the lumpectomy cavity with a small margin of 1-2 cm. It’s delivered in a shorter time of 1 week compared with about 6 weeks for standard whole breast radiation and 3-4 weeks for hypofractionated whole breast radiation.
The original method developed to deliver partial breast radiation is interstitial tube and button brachytherapy. This uses multiple small little tubes that are placed through the lumpectomy cavity to encompass the area at risk. One end of these tubes can be connected to a high dose rate brachytherapy machine that allows a motorized cable with a very small radiation source welded to the end of it to be temporarily pushed in and out of each of the tubes so that the patient can be treated from “inside out”. This helps concentrate the radiation to the area of the lumpectomy cavity while limiting exposure to normal tissues. This treatment is most commonly delivered as an out-patient two times per day for a total of 10 treatments.
The main finding from our paper is that in reviewing the outcomes on over 1,000 women treated with this technique with an average follow-up of 6.9 years that the 10 year actuarial local recurrence rate was 7.6% and in women with more than 5 years of follow-up physician reported cosmetic outcomes were excellent/good in 84% of cases.
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MedicalResearch.com Interview with:
Kristian Pietras, Ph.D.
Göran & Birgitta Grosskopf Professor of Molecular Medicine
Strategic Director of Cancer Research Lund University
Dept of Laboratory Medicine Lund
Div of Translational Cancer Research Lund, SwedenMedical Research: What is the background for this study? What are the main findings?
Dr. Pietras: Breast cancer is the largest malignant disease among women with 1.7 million new cases worldwide each year (25% of all new cancer cases for women). The prognosis for breast cancer patients is relatively good when the disease is detected at early stages (close to 90% of patients are still alive 5 years after diagnosis). Nevertheless, metastatic disease is the cause of 90% of all cancer-related deaths. Thus, learning more about the metastatic process and finding new cures for widespread disease is justifiably at the center of clinical attention.
The current study is part of our ongoing efforts to map support functions performed by the various cell types comprising the tumor stroma with the premise that decisive treatment benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that collectively sustain the growth of tumors. The development of a rich vascular supply is recognized as a key hallmark of a growing tumor necessary for the development into a clinically relevant disease.
Our focus is the role of the tumor vasculature in preventing or promoting metastatic dissemination from the primary tumor. For a metastasis to form, a cancer cell must,
1) detach from its neighboring cells in the mother tumor,
2) traverse the vascular wall to escape into the blood stream,
3) exit the vasculature to enter the metastatic site, and
4) colonize the metastatic site.
Recent evidence points to that the transmigration into and out of the vasculature is a regulated process of previously unrecognized importance for the metastatic process. Importantly, the fact that the process of escape into/from the vasculature is regulated also implies that it is possible to use drugs to block this process.
In the present study, we have combined functional studies in advanced models of cancer and computational biology approaches to investigate the specific contribution to the metastatic process of a molecular signaling pathway emanating from the ALK1 protein expressed by endothelial cells in the vasculature. Using information from 2 different patient cohorts including a total of nearly 2000 breast tumors, we found that patients specifically having high levels of ALK1 in the vasculature of their tumor were much more likely to develop metastatic/recurrent disease. Accordingly, therapeutic administration of a drug (dalantercept) blocking the action of ALK1 prevented metastatic dissemination in multiple mouse models of breast cancer to a large degree. In addition, combination therapy of dalantercept and a commonly used chemotherapeutic drug (docetaxel) was exceedingly effective in preventing spread of the primary tumor to the lungs.
Our results suggest that the molecular features of the tumor vasculature are important to consider as potential determinants of breast cancer dissemination and that metastatic spread can be delayed by targeting the tumor vasculature.
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MedicalResearch.com Interview with:
Isabelle Bedrosian, M.D., F.A.C.S.
Associate Professor, Department of Surgical Oncology, Division of Surgery,
Medical Director, Nellie B. Connelly Breast Center
The University of Texas MD Anderson Cancer Center, Houston, TX
Medical Research: What is the background for this study? What are the main findings?Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns.
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MedicalResearch.com Interview with:
Michaela Dinan, Ph.D.
Duke Clinical Research Institute and Duke Cancer Institute
Department of Medicine
Duke University School of Medicine
Durham, North Carolina
Medical Research: What is the background for this study? What are the main findings?
Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer. The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients.
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MedicalResearch.com Interview with:
Ying Wang, PHD | Senior Epidemiologist
American Cancer Society, Inc.
Atlanta, GeorgiaDr. 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.
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MedicalResearch.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.
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MedicalResearch.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.
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MedicalResearch.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. (more…)
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.
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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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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:
Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CA 94305-5826Medical 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. (more…)
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:
Dr. Alexandra White PhD in Epidemiology
University of North Carolina at Chapel Hill
Postdoctoral fellow
National Institute of Environmental Health Science
MedicalResearch: What is the background for this study?
Dr. White: Many studies have shown that being overweight or obese is a risk factor for postmenopausal breast cancer. We know less about how obesity impacts breast cancer risk in premenopausal women.
About a third of U.S. adults are obese, which is defined as having a body mass index (BMI) greater than 30. Similarly, the prevalence of abdominal obesity, measured by a person’s waist circumference, has increased by 10% in the last decade. In 2012, more than two-thirds of U.S. women had a waist circumference that indicated abdominal obesity.
Abdominal obesity may be a better predictor than BMI for breast cancer risk and other chronic diseases, because it is related to insulin resistance and can reflect metabolically active fat stores.
In order to understand how different types of obesity (overall vs. abdominal) influence breast cancer risk, we used information from >50,000 participants in the Sister Study. The Sister Study, led by scientists at the National Institute of Environmental Health Sciences, part of the National Institutes of Health investigates environmental and genetic risk factors for breast cancer.
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