Serotonin Receptors Tied To Weight Gain From Atypical Antipsychotic Medications

MedicalResearch.com Interview with:

Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077

Dr. Chen Liu

Chen Liu, Ph.D.
Assistant Professor
Departments of Internal Medicine and Neuroscience
Division of Hypothalamic Research
The University of Texas Southwestern Medical Center
Dallas, Texas 75390-9077 

MedicalResearch.com: What is the background for this study?

Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma.

On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief.

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Holes in Cigarette Filters Linked To Increase in Lung Adenocarcinomas

MedicalResearch.com Interview with:
Peter G. Shields, M.D.
Deputy Director, Comprehensive Cancer Center
James Cancer Hospital
Professor, College of Medicine
Julius F. Stone Chair in Cancer Research
The Ohio State University Columbus, OH

MedicalResearch.com: What do we know about the health effects of cigarette filters? 
Response:  The issue is that the design of the filters makes a cigarette even more dangerous, which can be regulated by the FDA. The issue is not about having a filter, but how they are made. And now we are changing the dialogue to the design of virtually all cigarettes. The holes on the filter are likely one reason the cigarettes of today are more dangerous.

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NSAIDS May Increase Mortality From Endometrial Cancer

MedicalResearch.com Interview with:

Theodore Brasky, PhD Research Assistant Professor Center of Excellence in Regulatory Tobacco Science Epidemiology College of Public Health The Ohio State University

Dr. Theodore Brasky

Theodore Brasky, PhD
The Ohio State University
Comprehensive Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is a significant amount of data to suggest that long-term, regular use of nonsteroidal anti-inflammatory drugs (NSAIDS; examples include aspirin and ibuprofen) are associated with reduced risks of several cancers. Although the data across studies are inconsistent, one such candidate is endometrial cancer, which is the most common gynecologic cancer. There is good evidence that the use of these medications is associated with improved prognosis among patients diagnosed with colon cancer. Despite the importance of inflammation in endometrial cancer progression, very few have examined whether use of NSAIDs is associated with risk of death or recurrence from the disease. The study we published is the first of its kind to examine NSAID use comprehensively and in a study of over 4,000 patients.

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Study Links Well-Water Arsenic To Increased Bladder Cancer Risk in New England

MedicalResearch.com Interview with:

Dr. Debra Silverman Sc.D Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics National Cancer Institute

Dr. Debra Silverman

Dr. Debra Silverman Sc.D
Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics
National Cancer Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor.

A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:

  • Naturally occurring arsenic from geological sources (released from rock deep in the earth)
  • Leaching of arsenic-based pesticides used on food crops many years ago. From the 1920s through the 1960s there was extensive agricultural use of arsenic-based pesticides. These compounds were used on food crops such as blueberries, apples and potatoes. Residue from the treatments may have leached into the ground water.

Intake of water containing high levels of arsenic is an established cause of bladder cancer, largely based on studies conducted in highly exposed populations. However, emerging evidence suggests that low-to-moderate levels of exposure may also increase bladder cancer risk.

To explore possible reasons for the excess incidence of bladder cancer in northern New England, we conducted a large, comprehensive population-based case-control study in Maine, New Hampshire and Vermont. We examined the role of known and suspected bladder cancer risk factors, with a focus on private well water consumption and arsenic levels in drinking water.

The major cause of bladder cancer is cigarette smoking. Some occupational exposures (e.g., exposure to metalworking fluids such as that experienced by metalworkers and some types of machine operators) are also associated with elevated risk. However, smoking and occupational exposures do not appear to explain the New England bladder cancer excess.

This study was funded and carried out by researchers in the NCI Division of Cancer Epidemiology and Genetics in collaboration with the Geisel School of Medicine at Dartmouth, the Departments of Health for Maine, New Hampshire, and Vermont, and the US Geological Survey.

We reported that heavy consumption of drinking water from private dug wells (which are shallow—less than 50 feet deep—and susceptible to contamination from manmade sources than drilled wells), established prior to 1960 (when arsenic-based pesticides were widely used), may have contributed to the longstanding bladder cancer excess in northern New England.

We saw that cumulative arsenic exposure from all water sources showed an increasing risk with increasing exposure (exposure-response relationship). Among the highest exposed participants, risk was twice that of the lowest exposure group. (Cumulative arsenic exposure is a measure of the average daily arsenic intake by number of days of arsenic exposure.)

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Hepatitis C Raises Risk of HPV Head and Neck Cancers

MedicalResearch.com Interview with:

Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030

Dr. Harrys Torres

Harrys A. Torres, MD, FACP, FIDSA
Associate Professor
Director of Hepatitis C Clinic
Department of Infectious Diseases, Infection Control and Employee Health
The University of Texas MD Anderson Cancer Center
Houston TX 77030

Medical Research: What is the background for this study? What are the main findings?

Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers.

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Early Breast Cancer Screening Recommended For Survivors of Childhood Hodgkin’s Lymphoma

MedicalResearch.com Interview with:

David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto

Dr. David Hodgson

David Hodgson, MD, MPH, FRCPC
Associate Professor
University of Toronto
Toronto, ON Canada  

MedicalResearch.com: What is the background for this study?

Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance.

MedicalResearch.com: What are the main findings?

Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have “false positive” tests – abnormal findings that are not really cancer.

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Genetics Study Points To Different Pathways For Melanoma Risk

MedicalResearch.com Interview with:

Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599

Dr. Nancy E. Thomas

Nancy E. Thomas, MD PhD
Department of Dermatology, University of North Carolina
Chapel Hill, NC 27599

Medical Research: What is the background for this study?

Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways.

Medical Research: What are the main findings?

Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development.

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No Increase Risk of Breast Cancer Recurrence With Antidepressants While On Tamoxifen

Reina Haque, PhD, MPH Research scientist Department of Research & Evaluation Kaiser Permanente Southern California Pasadena Calif

Dr. Haque

MedicalResearch.com Interview with:
Reina Haque, PhD, MPH

Research scientist
Department of Research & Evaluation
Kaiser Permanente Southern California
Pasadena Calif

Medical Research: What is the background for this study? What are the main findings?

Dr. Haque: Tamoxifen is a commonly prescribed generic drug taken by women with breast cancer to reduce their chances of developing a recurrence. Tamoxifen is recommended for five years, but has notable side effects, including hot flashes, night sweats and depression. Since hormone replacement therapy is not recommended to alleviate these symptoms in breast-cancer survivors, antidepressants have been increasingly prescribed for relief. Almost half of the 2.4 million breast-cancer survivors in the U.S. take antidepressants.

However, previous studies have suggested that antidepressants reduce tamoxifen’s effectiveness in lowering subsequent breast-cancer risk. This study was conducted to determine whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer.
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Young Black Colon Cancer Patients Have Greater Risk of Recurrence

Harry H. Yoon, MD Mayo Clinic Rochester, MN 55905MedicalResearch.com Interview with:
Harry H. Yoon, MD
Mayo Clinic
Rochester, MN 55905

Medical Research: What is the background for this study? What are the main findings?

Dr. Yoon: In the U.S., the survival of patients with colon cancer is known to differ by race, with individuals of black race having worse outcomes than those of white race.

However, it has been difficult to tease apart why the differences in survival exist.

It is generally believed that social or other non-biologic factors (eg, decreased access to care, suboptimal treatment) contribute to the discrepancy.  It’s also known that differences in the general medical condition of patients could affect how long a patient lives.

However, it is unknown whether there are race-based differences in the biology of colon tumors themselves.  This biology can be reflected in the genetic composition of tumors, as well as by whether and how quickly the cancer returns after the patient has undergone surgery and chemotherapy.

In addition, it is unknown whether race-based differences in biology may be related to the age of the patient at the time of diagnosis.  Blacks with colorectal cancer typically have an earlier age of onset than whites do.

A major barrier to addressing these questions are that there are very few large populations of colon cancer patients where everyone had the same disease stage and received uniform treatment, and where patients were monitored for years afterward specifically to see whether the cancer returned.  It is much harder to measure whether cancer has returned (ie, cancer recurrence), as compared to simply knowing whether a patient is alive or dead.  This difference is important, because knowing about cancer recurrence sheds more light on cancer biology than only knowing about patient survival, since many factors unrelated to cancer biology (eg., heart disease) can affect whether a person is alive or dead.

The most reliable data on cancer recurrence (not just patient survival) generally comes from patients who have enrolled in a clinical trial.  In the Alliance N0147 trial, all patients had the same cancer stage (ie, stage III), underwent surgery and received standard of care chemotherapy (ie, “FOLFOX”) after surgery.  Patients had uniform, periodic monitoring after chemotherapy to see if the cancer returned.

In other words, examining racial outcomes in this cohort largely eliminates some of the key factors (eg, decreased access to care, suboptimal treatment) that are believed to contribute to racial discrepancies, and provides a unique opportunity to determine if differences in cancer biology between races may exist.

This study was done to see if colon cancers are genetically different based on race, and whether race-based differences exist in cancer recurrence rates.

The study found that tumors from whites, blacks, and Asians were different in terms of the frequency of mutations in two key cancer-related genes, BRAF and KRAS.  Tumors from whites were twice as likely to have mutated BRAF (14% in whites compared to 6% in Asians and 6% in blacks).  Tumors from blacks had the highest frequency of KRAS mutations (44% in blacks compared to 28% in Asians and 35% in whites).  Tumors from Asians were the mostly likely to have normal copies of both genes (67% in Asians compared to 50% in blacks and 51% in whites).

Next, the study found that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites.  However, this discrepancy was only evident among young patients (ie, aged less than 50 years).  Almost 50% of younger black patients experienced colon cancer recurrence within 5 years, compared to ~30% of black patients over age 50, or compared to white or Asian patients regardless of age. The worse outcome among young blacks remained evident even after adjusting for many potential confounding factors, such as tumor grade, the number of malignant nodes, or the presence of BRAF or KRASmutations.  Because this question was examined in a clinical trial cohort of uniform stage and treatment, the role of multiple important potential confounders was diminished.

To our knowledge, this is the first report indicating that colon cancers from young black individuals have a higher chance of relapsing after surgery and chemotherapy, compared to those from white individuals.

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Breast Cancer Pattern Likely To Change as Population Ages

Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892MedicalResearch.com Interview with:
Philip S. Rosenberg, PhD
Biostatistics Branch, Senior Investigator
Division of Cancer Epidemiology and Genetics
National Cancer Institute, 9609 Medical Center Drive
Bethesda, MD 20892 

Medical Research: What is the background for this study? What are the main findings?

Dr. Rosenberg: It has been previously reported that breast cancer burden (number of new cases diagnosed in a year) is expected to rise in the future, mostly due to the aging of the female population in the US.

Also, it has been established that the age-adjusted breast cancer incidence rates (cases per 100,000 women per year) are increasing for invasive ER-positive cancers overall and decreasing for ER-negative cancers overall. When taken together, these two trends tend balance each other out, resulting in a somewhat flat breast cancer incidence rate overall. 

Though the overall trends for invasive breast cancer have been previously reported, this study uses a more refined forecasting method by including recent birth cohort patterns to forecast breast cancer to 2030 by age group, estrogen receptor-status, and invasive vs. in situ tumors.

New in this report are the findings for in situ tumors and the more granular break down by age, ER status, and invasive vs. in situ tumors both for rate and burden (number of cases).
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Aspirin and Ibuprofen May Reduce Bowel Cancer Risk in Lynch Syndrome

Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 AustraliaMedicalResearch.com Interview with:
Aung Ko Win, MBBS MPH PhD

Research Fellow
NHMRC Early Career Clinical Research Fellow
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health
The University of Melbourne VIC 3010
Australia

Medical Research: What is the background for this study?

Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome.

A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome. Continue reading

Tubal Ligation May Limit Spread Of Endometrial Cancer

MedicalResearch.com Interview with:
Ashley S. Felix, PhD

Bethesda, MD

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Felix: Endometrial cancer prognosis is strongly affected by disease stage, or the extent of spread from the primary site. Endometrial cancers can spread via the lymph nodes, blood vessels, through the uterine wall, or through the fallopian tube into the peritoneal cavity. The last of these mechanisms is poorly understood, but appears to be a more common mode of spread for aggressive histologic subtypes of endometrial cancer. We hypothesized that women who previously underwent tubal ligation (TL) and later developed endometrial cancer would have lower stage disease, possibly by blocking passage of tumor cells along the fallopian tubes. Further, we hypothesized that TL would be associated with better prognosis, due to its relationship with lower stage.

We found that women in our study who previously had tubal ligation were more likely to have lower stage endometrial cancer compared with women who did not report a previous tubal ligation. Specifically, tubal ligation was inversely associated with stage III and stage IV cancer across all subtypes of the disease, including aggressive histologic subtypes. Further, in statistical models of tubal ligation, tumor stage, and mortality, we observed no independent association with improved survival, suggesting that tubal ligation impacts mortality mainly through its effects on stage.

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Lymph Node Cancer Metastases Do Not Require Growth of New Blood Vessels

Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114MedicalResearch.com Interview with:
Timothy P. Padera, PhD
Edwin L. Steele Laboratories
Department of Radiation Oncology
MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School
Boston, Massachusetts 02114

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting. We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical models of spontaneous lymphatic metastasis, however there were no mechanistic data to explain these observations. Here, we developed a novel chronic lymph node window model to facilitate new discoveries in the mechanisms of growth and spread of lymph node metastases. Our new data provide pre-clinical evidence along with supporting clinical evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in adjuvant setting, particularly those involving lymph node metastases.

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Molecule May Help Ovarian Cancer Patients Overcome Chemotherapy Resistance

Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030MedicalResearch.com Interview with:
Wei Zhang, Ph.D., Professor

Department of Pathology
Director, Cancer Genomics Core Lab
University of Texas MD Anderson Cancer Center
Houston, Texas 77030

Medical Research: What is the background for this study? What are the main findings?

Dr. Zhang: Epithelial ovarian cancer remains the most lethal gynecological malignancy. The 5-year survival rate for patients with advanced ovarian cancer is only 30-40%, and acquired resistance to platinum is considered a major factor in disease relapse. A major challenge in cancer treatment is the resilient ability of cancer cells to repair DNA damage caused by chemotherapy agents.  In this study, we found that adding a molecule called miR-506 to standard chemotherapy can help cells overcome drug resistance, so that the chemotherapy drugs remain effective against ovarian cancer. This research supports a new combination approach, which may substantially benefit patients with this deadly disease.

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Breast Cancer Risk Reduction of Prophylactic Salpingo-Oophorectomy May Be Overestimated For Some BRCA1 Carriers

Bernadette A.M. Heemskerk-Gerritsen, Ph.D.		 Department of Medical Oncology Erasmus MC Cancer Institute Roterdam, the NetherlandsMedicalResearch.com Interview with:
Bernadette A.M. Heemskerk-Gerritsen, Ph.D.
Department of Medical Oncology
Erasmus MC Cancer Institute
Roterdam, the Netherlands

Medical Research: What is the background for this study? What are the main findings?

Dr. Heemskerk-Gerritsen: Women with a BRCA1 or BRCA2 mutation have substantially higher risks of developing both primary and contralateral breast cancer (BC) and ovarian cancer than women from the general population. Options to reduce these increased cancer risks include risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). The latter intervention obviously reduces the risk of developing ovarian cancer, but has been reported also to reduce the risk of developing a subsequent breast cancer with approximately 50%. However, studies on the efficacy of risk-reducing surgery in BRCA1/2 mutation carriers are confined to observational studies, thus challenging several methodological issues. Consequently, previous studies on breast cancer risk-reduction after RRSO may have been influenced by bias associated with selection of study subjects, bias associated with start of follow-up, or by confounding, and breast cancer risk-reduction may have been overestimated.

In the current study, we revisited the association between risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1/2 mutation carriers, focusing on the impact of different analytical methods and potential types of bias.

First, we replicated the analyses of four previously performed studies, to examine if our Dutch cohort was comparable with the cohorts used in the previous studies. We replicated the approximately 50% breast cancer risk reduction after RRSO in the Dutch cohort.

Second, we estimated the effect of RRSO on breast cancer risk in the Dutch cohort using a revised analytical approach for observational studies in BRCA1/2 mutation carriers in order to minimize bias as much as possible. Using this method of analysis, we found no evidence of first BC risk-reduction after RRSO in BRCA1/2 mutation carriers.

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‘Chemobrain’: Cognitive Impairment May Be a Form Of Cancer-Related PTSD

Dr. Kerstin Hermelink Senior psychologist  Dept. of Gynecology and Obstetrics Ludwig Maximilian University of MunichMedicalResearch.com Interview with:
Dr. Kerstin Hermelink
Senior psychologist
Dept. of Gynecology and Obstetrics
Ludwig Maximilian University of Munich

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all.

Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained.

Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis.

We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms.

Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer.

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Coffee May Lower Melanoma Risk

MedicalResearch.com Interview with:
Erikka Loftfield
Doctoral student at the Yale School of Public Health
Fellow at the National Cancer Institute

Medical Research: What is the background for this study? What are the main findings?

Response: Previous studies have reported conflicting results on the association between coffee drinking and melanoma. We sought to clarify this relationship using data from the large NIH-AARP Diet and Health Study. We followed over 400,000 retirees aged 50 to 71 years at study entry for an average of 10 years. Participants were asked to report typical coffee intake. During the course of follow-up nearly 3,000 cases of malignant melanoma occurred. In our study, we observed that individuals who reported the highest total coffee intake (4 cups/day) had about 20% lower risk of malignant melanoma compared with those who did not consume coffee.

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Risk-Benefits of Tamoxifen for Breast Cancer Prevention

https://medicalresearch.com/category/hepatitis-liver-disease/page/2/MedicalResearch.com Interview with:
Hazel B. Nichols, PhD
Assistant Professor, Department of Epidemiology
University of North Carolina
Gillings School of Global Public Health

MedicalResearch:What is the background for this study?

Dr. Nichols: Tamoxifen, a drug that is often used to treat breast cancer, has also been approved to prevent breast cancer in women who may be at high risk for developing the disease. Taking tamoxifen for 5 years can lower breast cancer risk by up to 48%. The United States Federal Drug Administration (FDA) approved tamoxifen for breast cancer prevention more than 15 years ago (in 1998) for women ages 35 and older who are at high risk of breast cancer and who are at low risk for serious side effects.

National estimates show that <1% of women who are eligible to use tamoxifen actually use it for breast cancer prevention. While tamoxifen lowers breast cancer risk it does cause hot flashes and may lead to serious side effects such as cataract, stroke, and uterine cancer. Women who start taking tamoxifen may also stop taking it before the recommended 5-years due to side effects.

We used a tool developed by scientists at the National Cancer Institute (NCI) to calculate whether the benefits of tamoxifen outweighed the risks for women in the Sister Study, a study of more than 50,000 U.S. and Puerto Rican women with a family history of breast cancer. The tool uses information on a woman’s age, race, breast cancer risk, menopausal status, and whether she had a hysterectomy (surgical removal of the uterus) to estimate whether there is no, moderate or strong evidence that the benefits of tamoxifen will outweigh the risks.

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BRCA Screening of Ashkenazi Women Would Be Cost Effective

MedicalResearch.com Interview with:
Dr Ranjit Manchanda
Consultant Gynaecological Oncologist, St Bartholomew’s Hospital, London, UK
Honorary Sr Lecturer, Women’s Cancer, EGA Institute for Women’s Health, University College London, UK  and
Professor Ian Jacobs
Vice President, The University of Manchester
Dean & Head School of Medicine
Faculty of Medical & Human Sciences, Director
MAHSC (Manchester Academic Health Science Centre)

Medical Research: What is the background for this study? What are the main findings?

Dr. Jacobs:  Background- Women carrying a BRCA1/2 gene alteration have a very high risk of developing breast and ovarian cancer and men carrying this alteration have an increased risk of prostate and breast cancer. Approximately 45-65% women who have this inherited genetic change will develop breast cancer and 15-35% ovarian cancer. They also have a 50% chance of passing these genes on to their children. At risk individuals can access available options of screening and prevention through the National Health Service (NHS). Some population groups across the world are known to have a higher frequency of BRCA 1/2 gene alterations than others. One example is Ashkenazi Jews who have a 1 in 40 likelihood of having a BRCA1/2 gene alteration. This is 10-20 times higher than in the general non-Jewish population.

At present in the UK, genetic testing is available within the NHS to individuals who have a strong family history of cancer. However, many people are not aware of their family history or its significance and do not seek advice. Many other individuals with BRCA1/2 gene alterations do not have a family history at all. The current approach misses a large number of people at risk who could benefit from knowing about their BRCA 1/2 mutation status and the ability to access opportunities for prevention or screening. In order to address this the GCaPPS study has investigated the best method of screening for risk of inherited (familial) cancer by exploring the alternative approach of offering the genetic test to all men and women >18 years in the Ashkenazi Jewish population. It does so by comparing the benefits and disadvantages of: (i) The current system of testing only those with a family history and (ii) The new option of testing everyone in the population.

Main Findings: Over half of the BRCA1/BRCA2 carriers detected did not give a strong family history of cancer and would not have been identified by current family history based testing criteria used in the NHS (National Health Service) in the UK and most health systems internationally. Reassuringly population-based genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life. A health economic analysis indicated that population-based screening for BRCA-mutations in Ashkenazi Jewish women ≥30years would be highly cost-effective compared to the traditional family history based approach. Such an approach if implemented could reduce the incidence of and deaths from breast and ovarian cancer as well as reducing cost and save the NHS funds.

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Breast Cancer: CYP2D6 Remains Important Biomarker of Tamoxifen Effectiveness

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo ClinicMedicalResearch.com Interview with:
Dr. Matthew P. Goetz, MD
Associate Professor of Pncology
Mayo Clinic

Medical Research: What is the background for this study? What are the main findings?

Dr. Goetz: There has been conflicting data with regard to the importance of tamoxifen metabolism as measured by CYP2D6 genetic variation.   Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy.   Our findings demonstrated that these studies were flawed in part based on analytical validity issues.  In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples.

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Prior Cancer Excludes Many Patients From Lung Cancer Trials

Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical CenterMedicalResearch.com Interview with:
Dr. David Gerber MD
Associate Professor of Internal Medicine
Division of Hematology and Oncology
Harold C. Simmons Cancer Center at UT Southwestern Medical Center

Medical Research: What are the main findings of the study?

Dr. Gerber: Fewer than 3% of adult cancer patients in the United States are enrolled in clinical trials.  Increasingly numerous and stringent eligibility criteria are a major factor limiting participation in clinical trials.  We examined the longstanding and widespread practice of excluding patients with prior cancer from oncology clinical trials.  This policy presumably reflects concerns that a prior cancer would interfere with the conduct, outcomes, or interpretation of a clinical trial, although there is no clear evidence supporting that assumption.

We examined more than 50 National Cancer Institute (NCI)-sponsored lung cancer clinical trials.  We found that 80% excluded patients with prior cancers.  This exclusion criterion was applied broadly, including to more than two-thirds of trials with non-survival endpoints.  We then examined national Surveillance Epidemiology and End Results (SEER)-Medicare linked data to estimate the proportion of patients who would be excluded from these trials due to prior cancer.  We found that up to 18% of potential patients are excluded for this reason alone.  In large phase 3 clinical trials, that corresponds to more than 200 patients.

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Engineering A Probiotic To Reduce Obesity

Sean Davies PhD Department of Pharmacology Vanderbilt UniversityMedicalResearch.com Interview with:
Sean Davies PhD
Department of Pharmacology
Vanderbilt University

Medical Research: What are the main findings of the study?

Dr. Davies: N-acyl phosphatidylethanolamine (NAPE) is a fat-like molecule normally produced by small intestine of mammals in response to eating high fat foods that helps signal a feeling of fullness to the brain.  This sensation of fullness is what normally helps us decide to stop eating, but in obese people it appears that not enough NAPE is produced so that not enough of that signal gets sent to the brain.  So we wanted to find a way to increase the amount of NAPE made in the intestinal tract, with the hope that this would help protect against obesity. Our approach was to engineer a probiotic bacteria that normally colonizes the gut of humans and other mammals so that it would make NAPE.  Our hope was that when this gut bacteria made the NAPE, it would be absorbed by the intestine and help supplement the NAPE already being made by the intestine so that a more complete sensation of fullness would be send to the brain.

What we found was that our engineered bacteria made a significant amount of NAPE and that when fed to mice, the bacteria would colonize the gut like normal and that the intestinal cells could absorb this NAPE.  Most importantly, we found that mice that received this bacteria ate less of the high fat diet than mice that were not treated or that received bacteria that did not make NAPE. Because the mice ate less of the high fat diet, and also because they burned the fat they had more effectively, the mice receiving the bacteria producing NAPE had only 50% of  the body fat of the control mice.  While the control mice showed the early signs of developing diabetes, the mice that received the NAPE producing bacteria showed almost no signs of developing diabetes. So the presence of these NAPE producing bacteria protected the mice from the harmful effects of the high fat diet.

Another key findings was that because the bacteria live in the GI tract and keep producing the NAPE for many weeks, we didn’t have to keep administering the bacteria to the mice to keep up the protective effect.  Even a month after we stopped giving the bacteria producing NAPE, the mice were still protected from the effects of the high fat diet.  Eventually after about six weeks, the bacteria died out and the mice started eating the same amount of food as the control mice, but even for at least another six weeks after this, they still weighed less than the control mice.

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Links Between Breast Cancer and Obesity Studied

Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine The University of Texas MD Anderson Cancer Center Department of Emergency Medicine Department of Endocrine Neoplasia & Hormonal Disorders Houston, Texas  77230-1402MedicalResearch.com Interview with
Sai-Ching Jim Yeung, MD, PhD, FACP
Professor of Medicine
The University of Texas MD Anderson Cancer Center
Department of Emergency Medicine
Department of Endocrine Neoplasia & Hormonal Disorders
Houston, Texas  77230-1402

MedicalResearch: What are the main findings of the study?

Dr. Yeung: We believe that this study has bridged a significant gap in knowledge between epidemiological data (the association of obesity and poor breast cancer prognosis) and biological mechanisms mediating the impact of obesity on cancer. This study provides an important mechanistic insight into the causal relationship between obesity and breast cancer growth.

  1. Direct evidence for the links between obesity-associated changes in the biological processes and hallmarks of cancer in human estrogen receptor-positive (ER+) breast cancer. 

It is well known that obesity is associated epidemiologicaly with decreased survival in ER+ breast cancer patients. Although a body of experimental literature exists to suggest important roles for estrogen, insulin/IGF-1 and adipokine signaling and inflammation in the mechanisms mediating the impact of obesity on cancer, direct evidence for these mechanisms and their importance relative to one another is lacking in cancers from obese humans.

Functional transcriptomic analysis of a prospective observation cohort with treatment-naïve ER+ breast cancer samples identified the insulin/PI3K signaling and secretion of cytokines among the top biological processes involved. Many of the obesity-associated changes in biological processes can be linked to cancer hallmarks.  Upstream regulator analysis identified estrogen (?-estradiol), insulin (INS1), insulin-like growth factor-1 (IGF1), and adipokines [vascular endothelial growth factor A (VEGFA), tissue necrosis factor (TNF), interleukin-6 (IL6), oncostatin-M (OSM), chemokine ligand 5 (CCL5), leptin (LEP), leukemia inhibitory factor (LIF), C-reactive protein (CRP), adiponectin (ADIPOQ), and interleukin-10 (IL10)] in mediating the impact of obesity on human ER+ breast cancer.

  1. Experimental evidence that obesity causes accelerated oncogene-driven ER+ breast cancer carcinogenesis.

While it is not possible to conduct a human experiment to prospectively examine the causal relationship between obesity and breast cancer, we created a transgenic mouse model with genetically induced obesity and oncogene-driven breast cancer.  With this model we found strong in vivo evidence using both longitudinal experiments and cross-sectional experiments that obesity accelerated oncogene-driven breast carcinogenesis.
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Aspirin and Lifestyle Changes May Modulate Colon Cancer Risk

Kaspar Truninger, MD, FMH Gastroenterology and Internal Medicine Langenthal, SwitzerlandMedicalResearch.com Interview with:
Kaspar Truninger, MD, FMH
Gastroenterology and Internal Medicine
Langenthal, Switzerland

MedicalResearch: What are the main findings of the study?

Dr. Truninger: In our study, we investigated the effect of lifestyle exposure on DNA methylation. We measured genome-wide promoter CpG methylation in 1092 normal colon biopsies from 546 healthy females. We observed that fewer CpGs acquired age-dependent methylation in users of aspirin and hormonal replacement therapy compared with nonusers, whereas more CpGs were affected in smokers and individuals with a body mass index > 25 compared with nonsmokers and less obese females. Half of the CpGs showing age-dependent methylation gain were hypermethylated in tissue of colorectal cancer. These loci gained methylation with a higher rate and were particularly susceptible to lifestyle exposure compared to age-only methylated CpGs. In addition, these CpGs were enriched for polycomb regions.  Finally, all effects were different according to the anatomic location along the colon.

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Prostate Cancer: Tomato Products May Reduce Risk

Edward Giovannucci, MD, ScD Department of Nutrition Harvard School of Public Health Boston, MAMedicalResearch.com Interview with:
Edward Giovannucci, MD, ScD
Department of Nutrition
Harvard School of Public Health
Boston, MA


MedicalResearch: What are the main findings of the study?

Dr. Giovannucci: In 50,000 men followed over 24 years, we found that those regularly consuming tomato products, which are high in lycopene, had a 30% lower risk of developing lethal prostate cancer. Among men being screened regularly with PSA, the risk reduction from high tomato consumption was 50%. We also examined the prostate cancer tissue and found that higher dietary lycopene intake was associated with less new blood vessel formation, which may help explain why the cancers were less likely to progress.
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Breast Cancer: High Fat Diet Raises Risk of Hormone Sensitive Cancer

dr_sabina-sieriMedicalResearch.com Interview with:
Sabina Sieri, PhD
Epidemiology and Prevention Unit
Department of Preventive & Predictive Medicine
Fondazione IRCCS Istituto Nazionale dei Tumori
20133 Milan – Italy

MedicalResearch.com: What are the main findings of this study?

Dr. Sieri: In our study we found that there was an increased risk of developing breast cancer from high saturated fat intake. High total and saturated fat intake were associated with greater risk of ER PR positive breast cancer. High saturated fat intake was also associated with a greater risk of HER2 negative disease. So, a high-fat diet increases breast cancer risk and, most conspicuously, a high saturated fat intake increases the risk of developing hormone-sensitive diseases, suggesting saturated fat involvement in the etiology of hormone-sensitive breast cancer.

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Breast Cancer Survivors: Increased Marker of Aging Accompanies Standard Chemotherapy

Hanna Sanoff MD, MPH Lineberger Comprehensive Cancer Center Department of Medicine University of North Carolina, Chapel Hill, NCMedicalResearch.com Interview with:
Hanna Sanoff MD, MPH
Lineberger Comprehensive Cancer Center
Department of Medicine
University of North Carolina, Chapel Hill, NC


MedicalResearch.com: What are the main findings of the study?

Dr. Sanoff: We measured p16, a protein that increases with cellular aging, in blood cells of women receiving chemotherapy for breast cancer. We found that a standard course of chemotherapy led to an increase in p16 expression equivalent to what we have previous seen in people over the course of 10-15 years of chronological aging. This increase persisted in cancer survivors an average of three and half years after treatment.
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Mucin Profiling of Pancreatic Cysts to Improve Pancreatic Cancer Detection

Dr. Karolina Sjöberg Jabbar, MD, Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital Gothenburg, SwedenMedicalResearch.com Interview with
Dr. Karolina Sjöberg Jabbar, MD,

Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital
Gothenburg, Sweden

 

MedicalResearch.com: What are the main findings of the study?

Answer: The main finding of this study is that the presence of mucin proteins in pancreatic cyst fluid, as evaluated by mass spectrometry, can predict with high accuracy (97%) which pancreatic cysts contain premalignant and malignant tumours. This is important, given that pancreatic cystic lesions are an increasingly common incidental finding on imaging. While most of them pose no threat to the patient, a minor proportion has malignant potential, and may be considered precursors to pancreatic cancer.

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Castration-Resistant Prostate Cancer: Serum Biomarkers of Bone Metabolism

Primo N. Lara, Jr, MD, Professor of Medicine, University of California Davis School of Medicine Associate Director for Translational Research UC Davis Comprehensive Cancer Center Sacramento, CA 95817MedicalResearch.com Interview with:
Primo N. Lara, Jr, MD,
Professor of Medicine, University of California Davis School of Medicine
Associate Director for Translational Research
UC Davis Comprehensive Cancer Center
Sacramento, CA 95817

MedicalResearch.com: What are the main findings of the study:

Dr. Lara:  “We found that blood markers of bone turnover can be used to predict outcomes in men with advanced prostate cancer with spread to bone. We also found that a small proportion of men could be predicted to benefit from an investigational drug based on these same markers.”
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Colon Cancer Patients Have Less Diverse Gut Bacteria

MedicalResearch.com Interview with:
Jiyoung Ahn, PhD Assistant Professor of Epidemiology Department of Population Health NYU School of Medicine New York, NY 10016Jiyoung Ahn, PhD
Assistant Professor of Epidemiology
Department of Population Health
NYU School of Medicine
New York, NY 10016


MedicalResearch.com: What are the main findings of the study?

Dr. Ahn: Before we did our research, it was suspected that gut bacteria were related to colorectal cancer. We, for the first time, found colorectal cancer patients have a different gut bacteria composition than healthy subjects.

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Breast Cancer Risk: Increased by Pre- First Pregnancy Alcohol Intake

MedicalResearch.com Interview with:

Ying Liu, MD, PhD
Instructor, Division of Public Health Sciences
Department of Surgery
Washington University School of Medicine
660 South Euclid Ave Campus Box 8100
St. Louis, MO 63110

MedicalResearch.com: What are the main findings of the study?

Answer: Alcohol intake between menarche (first menstrual period) and first pregnancy was consistently associated with increased risks of breast cancer and proliferative benign breast disease. For every 10 gram/day alcohol intake (approximately a drink a day) during this specific time period, the risk for breast cancer increased by 11% and the risk for proliferative benign breast disease increased by 16%.
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Lung Cancer: Micropapillary Morphology To Guide Resection vs Lobectomy Choice

Prasad Adusumilli MD, FACS Associate Member, Thoracic Surgery Memorial Sloan-Kettering Cancer Center New YorkMedicalResearch.com Interview with: Prasad Adusumilli MD, FACS
Associate Member, Thoracic Surgery
Memorial Sloan-Kettering Cancer Center
New York


MedicalResearch.com: What are the main findings of the study?

Answer: The current standard of care of for early-stage lung adenocarcinoma, the common form of lung cancer is curative-intent surgery either by limited resection, LR (removal of tumor with clear margins) or lobectomy, LO (removal of one-third to one-half of the lung harboring the tumor). Although lung-sparing LR is preferable, there is a reported incidence of 30-40% of recurrences within the same lung. The causative factor/s for these local recurrences is not known.

In our study, we analyzed recurrence patterns and pathological features in patients who underwent 476 LO and 258 LR performed at the Memorial Sloan-Kettering Cancer Center, New York. We investigated the morphological patterns in pathology specimens utilizing the recently proposed International Association for the Study of Lung Cancer / European Respiratory Society / American Thoracic Society (IASLC/ERS/ATS) classification. We noticed that presence of micropapillary morphology was associated with three times higher recurrences in patients undergoing LR compared to LO, these recurrences were lower when there is an adequate margin (2 cm) resected beyond the tumor. In patients undergoing LO, the recurrences were 75% less.
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HIV-Lymphoma Survival – Not Improving in Anti-Retroviral Therapy Era

MedicalResearch.com Interview with: Satish Gopal, MD, MPH
Program in Global Oncology, Lineberger Comprehensive Cancer Center
UNC Project-Malawi, Tidziwe Center, Private Bag A-104, Lilongwe, Malawi

MedicalResearch.com: What is the primary message our physician readers should take away from the piece?”

Answer: Lymphoma is one of the leading causes of HIV-associated death in the modern ART era. In our analyses of a large multicenter US cohort, survival for HIV-associated lymphoma patients receiving routine care has not clearly improved since the modern ART era began, and remains significantly worse than SEER outcomes for the same lymphoma subtypes in the general population. This was somewhat surprising in an era of normalizing life expectancy for HIV-infected patients on ART, and quite different from the outstanding results achieved for this population in recent clinical trials conducted by AMC and NCI.
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Regional Variation in Spending and Survival for Older Adults With Advanced Cancer

Gabriel Brooks MD Fellow, Medical Oncology Dana-Farber Cancer InstituteMedicalResearch.com Interview with Gabriel Brooks MD
Fellow, Medical Oncology
Dana-Farber Cancer Institute

MedicalResearch.com: What are the main findings of the study?

Dr. Brooks: First, we found that there is substantial regional variation in Medicare spending for patients with advanced cancer.  For patients with a new diagnosis of advanced stage cancer, spending in the six months following diagnosis varied by 32% between regions in the highest and lowest quintiles of spending.  And for patients who died from cancer, spending in the last six months of life varied by 41% between the highest and lowest spending regions.

Second, we tested the association between area-level spending and survival from the time of advanced cancer diagnosis.  We found that there was no consistent association between increasing spending and survival for any of the five cancer sites included in our study (non-small cell lung cancer, colorectal cancer, pancreas cancer, breast cancer and prostate cancer).
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Selection Criteria for Lung-Cancer Screening

Dr. Martin C. Tammemägi  Professor (Epidemiology) Brock University Department of Community Health Sciences Walker Complex – Academic South, Room 306 St. Catharines, Ontario, Canada L2S 3A1Medical Research.com
Author Interview: Dr. Martin C. Tammemägi

Professor (Epidemiology) Brock University
Department of Community Health Sciences
St. Catharines, Ontario, Canada L2S 3A1

Medical Research.com What are the main findings of the study? 

Dr. Tammemägi: Our study accomplished three things:

1. We presented an updated Lung Cancer Risk Prediction Model, which compared to our previously JNCI-published model, incorporates more predictors but is simpler to use because we changed the way we modeled nonlinear effects.

2. We demonstrated that using the Lung Cancer Risk Prediction Model to select individuals for lung cancer screening was much more effective than using the National Lung Screening Trial (NLST) enrolment criteria.  41.3% fewer lung cancers were missed.  Sensitivity and positive predictive value of identifying individuals who develop lung cancer were significantly improved.  Shortly after our NEJM paper was published, Ma et al published in CANCER their findings that 8.6 million Americans are NLST-criteria positive and if they were CT screened under ideal conditions 12,000 lung cancer deaths would be averted.  Our NEJM article findings indicate that an additional 2,764 lives would be saved if the selection criteria had enrolled 8.6 million individuals for screening based on highest risk by our Lung Cancer Risk Prediction Model.

3. Importantly, using NLST data we demonstrated that the beneficial effect of CT screening did not vary by model predicted lung cancer risk.
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