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Helping patients understand colonoscopy alternatives and make a colorectal cancer screening choice based on their own values -- combined with one-on-one support -- dramatically increases screening completion among patients with historically lower screening rates, a new study finds. Colorectal cancer is the second leading cause of cancer death in the United States. In the Journal of the American Medical Association Internal Medicine, researchers from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center report a 40 percent increase in screening rates for patients at two community health centers in North Carolina and New Mexico using a decision aid and support from a trained navigator. Michael Pignone, M.D., a former researcher at UNC and chair of the Department of Internal Medicine at Dell Medical School at The University of Texas at Austin, co-authored the study. "This study gives us one model for effective health interventions in vulnerable populations," said Pignone. "There's no doubt that colon cancer screening is beneficial when implemented in the right age group. The question is, how far are care providers willing to go to bring those benefits to people with barriers to screening?" Regular screening for colorectal cancer is recommended for people between 50 and 75 years of age. But research shows rates are low in some groups, particularly for people who are low-income, on Medicaid, have limited English proficiency and some minority groups. The majority of the 265 patients in the UNC study fit the profile of those with typically lower screening rates. "We've shown that if we structure care such that we catch patients right when they are seeing their doctor, systematically provide them with clear and compelling information about screening and what their choices are, and then give them personal support they need to get the screening test they prefer, we can substantially improve rates," said the study's lead author, Dan Reuland, M.D., MPH, a UNC Lineberger member and professor in the UNC School of Medicine. Before their appointments, patients watched a decision-aid video in English or in Spanish (per primary language) about their colon cancer screening options, which include colonoscopy or a home test that allows patients to mail in a sample of their stool. Then, patients met one-on-one with a navigator who followed up about their plans for a colonoscopy appointment or home tests. Overall, 68 percent of patients who watched the video and met with a patient navigator were screened for colorectal cancer within six months, compared with 27 percent of patients who did not receive the intervention. "Colonoscopy is just one of several screening tests recommended by the U.S. Preventive Services Task Force," said Alison Brenner, PhD, MPH, associate program director of the Decision Support Lab at UNC's Cecil G. Sheps Center for Health Services Research. "Studies have shown that offering colonoscopy only results in lower adherence to screening than offering a choice, and our study appears to confirm that." The video aid helped patients make an informed discussion with their physician about screening and share in decision-making. Due to time constraints of appointments, physicians aren't always able to elicit patients' preferences regarding screening tests, but this intervention facilitated the conversation. Combining the decision aid with support from a trained navigator also contributed to the success, researchers concluded. Navigators helped to make sure patients received a stool test kit if they wanted it, completed the test, accessed financial assistance programs, and scheduled a colonoscopy if needed. Shared decision-making is a key component of patient-centered health care, one that Dell Medical School is embedding into its curriculum, clinical care and community outreach efforts, Pignone said. He plans to adapt the principles from the UNC study to initiatives in Travis County to measurably improve health in the community. One barrier to replicating the intervention model is the cost to community health centers for navigator salaries. Follow-up studies are planned to analyze the cost-effectiveness of the method so that it could be improved and implemented in a value-based health care framework. In addition to Reuland, Brenner and Pignone, study authors include: Richard Hoffman, M.D., MPH; Andrew McWilliams, M.D., MPH; Robert Rhyne, M.D.; Christina Getrich, Ph.D.; Hazel Tapp, Ph.D.; Mark A. Weaver, Ph.D.; Danelle Callan, M.A.; Laura Cubillos, MPH; and Brisa Urquieta de Hernandez. The study was primarily supported by the American Cancer Society. Additional funding was provided by the University of New Mexico Clinical and Translational Science Center, the North Carolina Translational and Clinical Sciences Institute at the University of North Carolina, and UNC Lineberger. Individual researchers were supported by the Agency for Healthcare Research and Quality's National Research Service Award, and the National Center for Advancing Translational Sciences.


CHAPEL HILL - Alcohol consumption is known to be a risk factor for breast cancer based on studies predominantly done in white women. Now a University of North Carolina Lineberger Comprehensive Cancer Center study has found the same risk exists for black women, an understudied group. Researchers found in the new study that black women who drank more than 14 alcoholic drinks per week had a significantly higher risk of invasive breast cancer than those who drank less. The findings, published in the journal Cancer, Epidemiology, Biomarkers & Prevention, confirmed the link between alcohol consumption and breast cancer risk, which has been seen in other studies drawn from majority white populations. And while some breast cancer risk factors - like age or genetics -- aren't easily modified, alcohol consumption is one risk factor that women, regardless of race, can change to potentially lower their cancer risk. "Minority groups are often understudied because they represent a smaller proportion of study populations. This work avoided that limitation by working with a consortium of many different studies, including more than 20,000 black women," said Melissa Troester, PhD, a member of UNC Lineberger and professor of epidemiology in the UNC Gillings School of Global Public Health. "We found that the patterns observed in other studies examining alcohol and breast cancer risk hold in black women, too." The researchers analyzed data for 22,338 women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, which combines data from four large breast cancer studies. Researchers evaluated alcohol as a risk factor for invasive breast cancer as well as for specific breast cancer subtypes, such as estrogen receptor positive or negative cancer. "Our study demonstrated there is benefit in creating consortia to focus on understudied groups," said the study's first author Lindsay Williams, a graduate research assistant at UNC Gillings. When they studied the data across all breast cancer subtypes, they found consuming seven or more alcoholic drinks per week was linked to increased risk of breast cancer across all subtypes. Women who previously drank alcohol, and later stopped, had lower risk than women who reported recent use - indicating that women may be able to reduce their risk by drinking less. However, they did find significantly higher risk for some women who have never drank alcohol. The researchers said that the group of women that avoids alcohol also sometimes includes women who have other health conditions, and some of these health conditions can increase risk for breast cancer. The finding may direct additional research. "In the future, it may be worth-while to better characterize women who identify as never drinkers to understand reasons for abstaining from alcohol," Williams said. The researchers underscored that the study is important as alcohol consumption can be changed or addressed. "Overall, our findings among African American women mirror those reported in the literature for white women, namely that high levels of alcohol intake - more than one drink per day - are associated with increased breast cancer risk," Troester said. "Alcohol is an important modifiable exposure, and women who are concerned about their risk of breast cancer could consider reducing levels of exposure." In addition to Troester and Williams, other authors include: Andrew F. Olshan, Chi-Chen Hong, Elisa V. Bandera, Lynn Rosenberg, Ting-Yuan David Cheng, Kathryn L. Lunetta, Susan E. McCann, Charles Poole, Laurence N. Kolonel, Julie R. Palmer, and Christine B. Ambrosone. The study was supported by the National Institutes of Health, the Komen for the Cure Foundation, the Breast Cancer Research Foundation and the University Cancer Research Fund.


News Article | May 1, 2017
Site: www.futurity.org

While brain inflammation is a major part of neurodegenerative diseases including multiple sclerosis, Alzheimer’s, Parkinson’s, ALS, and others, comparatively little is known about its causes and exact role in various diseases. Now, researchers may have made a key discovery about the molecular trigger for brain inflammation, a new study suggests. In a study published in the Journal of Experimental Medicine, researchers identified key molecules that drive brain inflammation in a mouse model of multiple sclerosis—molecules that are present at abnormally high levels in the brains of humans with the disease. The findings show that these inflammatory molecules are ripe targets for further study and potential targets for future multiple sclerosis treatments. The research may also lead to a better understanding of Alzheimer’s, traumatic brain injury, stroke, and other diseases that involve neuroinflammation. “We need to better understand brain inflammation at the molecular level in order to treat neurodegenerative conditions,” says Jenny Ting, a professor of genetics at University of North Carolina at Chapel Hill, who is also a member of the university’s Lineberger Comprehensive Cancer Center. “Our study shows how two proteins that control inflammation are crucial to a particular kind of brain inflammation.” The study began as an investigation of LPC (lysophosphatidylcholine), a fat-related signaling molecule that researchers have suspected stokes harmful brain inflammation in multiple sclerosis and other central nervous system diseases. In initial experiments, study co-lead authors—postdoctoral researcher Haitao Guo, graduate student Leslie Freeman, and former graduate student Sushmita Jha—found evidence that LPC triggers the inflammatory activation of mouse immune cells through two proteins called NLRP3 and NLRC4. NLRP3 and NLRC4 are components of the so-called innate immune system—a network of infection-fighting molecules and cells evolutionarily older than the better-known adaptive immune system’s T-cells, B-cells, and antibodies. Like other NLR-family proteins, NLRP3 and NLRC4 appear to have evolved to detect molecular patterns associated with certain microbes. The two proteins trigger inflammation in response to these microbes. There is evidence, too, that NLR-family proteins can trigger inflammation in response to non-microbial signals related to tissue damage. LPC is suspected to be one such kind of signal, and it is this sort of non-microbial tissue inflammation that researchers think is involved in neurodegenerative diseases. In previous studies, NLRP3 was shown to be a factor in brain inflammation in multiple sclerosis and Alzheimer’s disease. But no one had reported a brain inflammation role for NLRC4 in neurodegenerative diseases involving animal models. To investigate that possibility, Freeman, Guo, and Jha examined mouse astrocytes and microglia—resident brain cells that can perform immune functions in the nervous system. These cells are usually the main sources of inflammation in neurodegenerative diseases. Ting’s team found that LPC could induce an inflammatory response in these brain cells, as well, in a way dependent on NLRP3 and NLRC4. The researchers then worked with a mouse model of multiple sclerosis. They used a chemical called cuprizone to induce brain inflammation. This chemical also helped them strip the fatty layer surrounding nerve fibers. They found that the usual inflammatory activation of astrocytes and microglia, along with the stripping of nerve fibers, was greatly reduced when the mice lacked the genes for both NLRP3 and NLRC4. “Essentially, we saw a profound reduction of the inflammatory disease in these mice,” Guo says. “And where just one of those genes was absent, we didn’t see as pronounced a reduction of inflammation.” Underscoring the likely clinical relevance of these findings, the group found high levels of NLRC4 in astrocytes and microglia from the brain-inflamed mice, as well as in biopsied brain tissue from multiple sclerosis patients. Affected mouse and human brain tissue also showed abnormally high levels of an LPC cell receptor protein called G2A. “This is direct evidence of the importance of NLRC4 and NLRP3 in astrocytic and microglial inflammation, and we showed that this damage-associated molecule called LPC triggers the inflammation,” says Guo. The National Multiple Sclerosis Society and National Institutes of Health funded this work.


News Article | April 24, 2017
Site: www.eurekalert.org

CHAPEL HILL -- Although the health risks associated with indoor tanning are clear, tanning bed use among college-aged women is still popular. A new study by UNC Lineberger Comprehensive Cancer Center researchers suggests that adding images depicting the longer-term impacts of indoor tanning might be an effective health risk communication strategy. The researchers report in the Journal of Health Communication that anti-tanning bed messages with images showing some of the longer-term effects, such as skin cancer or wrinkles, produced greater negative emotional reactions and higher ratings of effectiveness in a survey of female college students. "Reducing tanning bed use would lead to reductions in skin cancer, and this is a 'winnable battle,'" said study co-author Seth Noar, PhD, a UNC Lineberger researcher and professor in the UNC School of Media and Journalism. "Indoor tanning is clearly a modifiable behavior - no one needs to lay in a tanning bed." Ninety percent of cases of melanoma, the deadliest skin cancer, are caused by exposure to ultraviolet light, the researchers report. A 2009 study found tanning beds' fluorescent bulbs generate UV radiation that is three times more intense than the sun. Indoor tanning is most common among younger, non-Hispanic white women. According to the 2010 National Health Interview Survey, as many of 32 percent of women aged 18 to 21 years used tanning beds, and 30 percent of white women aged 22 to 25 years reported using them. And according to the Skin Cancer Foundation, people who start indoor tanning before age 35 increase their risk of melanoma by 59 percent. Yet few studies have looked at messages to deter women from using tanning beds, Noar said. "This lack of research means we know little about what kinds of messages campaigns and other communications should focus on, and little about what would make an effective warning message," he said. "This study gives us some guidance as to what makes more effective messages targeting young women who use tanning beds or are thinking about using tanning beds." To identify which type of messages would be most effective, researchers surveyed 568 women enrolled at a university about the effectiveness of different messages viewed online. The study found messages with images produced greater negative emotional reactions, and were perceived as more effective in discouraging tanning than text-only messages. Messages that showed the longer-term health effects, like skin cancer and eye damage, and appearance-related side effects, like wrinkled skin, were rated as more effective among young women than images showing immediate tanning risks, like burns and infections. "Many young women who tan indoors are already familiar with the long-term health effects, but communicating these risks using visuals is much more hard-hitting than just text," said the study's first author Jennah Sontag, a doctoral candidate in the UNC School of Media and Journalism. "Because many women tan indoors to 'improve' their appearance, they should understand that their appearance is actually at-risk in the long-term," she added. Interestingly, they also saw that those surveyed said many of the text-only messages were more believable than those that included images. The researchers concluded that warnings should include images, but additional research is needed to make sure the images are realistic and believable. The study findings have the greatest implications for a print or even social media-based health communication campaign, Noar said, although they could be relevant to warnings on tanning beds themselves. "The FDA re-classified tanning beds into a stricter device category in September of 2014, and this included stronger warnings on tanning beds," Noar said. "However, the new warnings do not include images, and it is unclear whether they have impact. Our tanning research is very consistent with previous work in tobacco, and suggests that these kinds of warnings would be more effective if they were to visually depict real tanning harms such as melanoma, permanent eye damage, and premature skin aging." The study was supported by UNC Lineberger and the University Cancer Research Fund.


News Article | April 27, 2017
Site: www.biosciencetechnology.com

Brain inflammation is a key component of multiple sclerosis, Alzheimer’s, Parkinson’s, ALS, and most other major neurodegenerative diseases. How inflammation starts, how it’s sustained, and how it contributes to these diseases is not well understood, but scientists from the University of North Carolina School of Medicine have just found some important clues. In a study published in the Journal of Experimental Medicine, UNC researchers led by Jenny Ting, Ph.D., the William R. Kenan Distinguished Professor of Genetics, identified key molecules that drive brain inflammation in a mouse model of multiple sclerosis – molecules that are present at abnormally high levels in the brains of humans with the disease. The findings show that these inflammatory molecules are ripe targets for further study and potential targets for future multiple sclerosis treatments. The research may also lead to a better understanding of Alzheimer’s, traumatic brain injury, stroke and other diseases that involve neuroinflammation. “We need to better understand brain inflammation at the molecular level in order to treat neurodegenerative conditions,” said Ting, who is also a member of the UNC Lineberger Comprehensive Cancer Center. “Our study shows how two proteins that control inflammation are crucial to a particular kind of brain inflammation.” The study began as an investigation of LPC (lysophosphatidylcholine), a fat-related signaling molecule that researchers have suspected stokes harmful brain inflammation in multiple sclerosis and other central nervous system diseases. In initial experiments, study co-lead authors – UNC postdoctoral researcher Haitao Guo, PhD, graduate student Leslie Freeman, and former graduate student Sushmita Jha, PhD (now an assistant professor at the Indian Institute of Technology Jodhpur) – found evidence that LPC triggers the inflammatory activation of mouse immune cells through two proteins called NLRP3 and NLRC4. NLRP3 and NLRC4 are components of the so-called innate immune system – a network of infection-fighting molecules and cells evolutionarily older than the better-known adaptive immune system’s T-cells, B-cells, and antibodies. Like other NLR-family proteins, NLRP3 and NLRC4 appear to have evolved to detect molecular patterns associated with certain microbes. The two proteins trigger inflammation in response to these microbes. There is evidence, too, that NLR-family proteins can trigger inflammation in response to non-microbial signals related to tissue damage. LPC is suspected to be one such kind of signal, and it is this sort of non-microbial tissue inflammation that researchers think is involved in neurodegenerative diseases. In previous studies, NLRP3 was shown to be a factor in brain inflammation in multiple sclerosis and Alzheimer’s disease. But no one had reported a brain inflammation role for NLRC4 in neurodegenerative diseases involving animal models. To investigate that possibility, Freeman, Guo, and Jha examined mouse astrocytes and microglia – resident brain cells that can perform immune functions in the nervous system. These cells are usually the main sources of inflammation in neurodegenerative diseases. Ting’s team found that LPC could induce an inflammatory response in these brain cells, as well, in a way dependent on NLRP3 and NLRC4. The researchers then worked with a mouse model of multiple sclerosis. They used a chemical called cuprizone to induce brain inflammation. This chemical also helped them strip the fatty layer surrounding nerve fibers. They found that the usual inflammatory activation of astrocytes and microglia, along with the stripping of nerve fibers, was greatly reduced when the mice lacked the genes for both NLRP3 and NLRC4. “Essentially, we saw a profound reduction of the inflammatory disease in these mice,” Guo said. “And where just one of those genes was absent, we didn’t see as pronounced a reduction of inflammation.” Underscoring the likely clinical relevance of these findings, the group found high levels of NLRC4 in astrocytes and microglia from the brain-inflamed mice, as well as in biopsied brain tissue from multiple sclerosis patients. Affected mouse and human brain tissue also showed abnormally high levels of an LPC cell receptor protein called G2A. “This is direct evidence of the importance of NLRC4 and NLRP3 in astrocytic and microglial inflammation, and we showed that this damage-associated molecule called LPC triggers the inflammation,” said Guo.


News Article | May 3, 2017
Site: www.eurekalert.org

COLUMBUS, Ohio - More than half of breast cancer patients (57 percent) undergoing mastectomy lack the necessary medical knowledge to make a high-quality decision about reconstructive surgery that aligns with their personal goals, suggesting a trend toward overtreatment, according to a new study conducted by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). "High-quality" decisions were defined as those that demonstrated adequate medical knowledge of treatment choices - including associated risks - and that also matched with the patient's specific goals and preferences for choosing whether or not to pursue reconstructive surgery. Researchers say shared decision-making tools are needed to help women make decisions based on a full understanding of treatment choices and associated risks alongside their personal goals for surgery. Researchers report the findings online first in the medical journal JAMA Surgery May 3, 2017. In this observational, single-institution study, researchers sought to evaluate the quality of 126 adult breast cancer patients' decisions about breast reconstruction after mastectomy. All patients had stage I-III invasive ductal/lobular breast cancer, ductal carcinoma in situ (DCIS) or were having preventive mastectomies. The majority of patients (73 percent) had early-stage disease. Researchers measured study participants' medical knowledge about mastectomy and mastectomy with reconstruction -- for example, effects of surgery on appearance and associated risks. They also measured individual preferences of what mattered most to patients. Key preference factors included breast appearance/shape post treatment, length of recovery time and risk for complications. "We found that less than half of the women had adequate medical knowledge about breast reconstruction and made a choice that aligned with their personal preferences. This is very concerning to us, because it means that some women did not get the treatment they truly preferred, and quite a few had more treatment than they preferred," says Clara Lee, MD, principal investigator of the study and a breast reconstructive surgeon at The OSUCCC - James. Lee holds a dual associate professor appointment in the colleges of medicine and public health at Ohio State. "Many women were quite concerned about complication risks, but they didn't actually know how high the risk was. This may explain some of the overtreatment that we saw," she adds. Researchers found that only 43 percent of the patients in the study demonstrated an understanding of at least half of the important facts about reconstruction and made a choice that was consistent with their preferences. Understanding of surgical complications was particularly low, with only 14 percent of patients demonstrating strong knowledge of associated risks. "As breast cancer providers, we need to talk about the pros and cons of surgery to help women make treatment choices. Shared decision-making between the surgeon and patient would be particularly useful for this decision. We need to connect patients with decision aids to help them really think through what is most important to them," Lee adds. Collaborators in this National Cancer Institute-funded study include Allison Deal, MD, and Ruth Huh, BA, of Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill; Michael Pignone, MD, MPH, of University of Texas at Austin; and Peter Ubel, MD, of Duke University. "The interesting thing is that these findings are not unique to breast reconstruction," adds Pignone, study coauthor and chair of the Department of Internal Medicine at the Dell Medical School at The University of Texas at Austin. "In other places where we've looked at decision quality, we see gaps in patients' understanding of key information and poor alignment between the things they care most about and the treatments that they choose. It means that we need to do a much better job of providing decision support to patients, so that the care they get is, ultimately, the care they want." Lee and colleagues in Ohio State's colleges of engineering, communication and public health are working on a study to evaluate treatment decisions in early-stage breast cancer patients to assess how communication with their providers affects their decision-making. This ongoing study examines patients' knowledge, preferences, and expectations about future well-being. Information from this study is expected to help clinicians develop tools to aid patients in making an informed decision about their care. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 47 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. Learn more at cancer.osu.edu.


News Article | May 3, 2017
Site: www.eurekalert.org

More than half of breast cancer patients (57 percent) undergoing mastectomy lack the necessary medical knowledge to make a high-quality decision about reconstructive surgery that aligns with their personal goals, suggesting a trend toward overtreatment, according to a new study conducted at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). "High-quality" decisions were defined as those that demonstrated adequate medical knowledge of treatment choices -- including associated risks -- and that also matched with the patient's specific goals and preferences for choosing whether or not to pursue reconstructive surgery. Researchers say shared decision-making tools are needed to help women make decisions based on a full understanding of treatment choices and associated risks alongside their personal goals for surgery. Researchers report the findings online first in the medical journal JAMA Surgery May 3, 2017. In this observational, single-institution study, researchers sought to evaluate the quality of 126 adult breast cancer patients' decisions about breast reconstruction after mastectomy. All patients had stage I-III invasive ductal/lobular breast cancer, ductal carcinoma in situ (DCIS) or were having preventive mastectomies, and the majority (73 percent) had early-stage disease. Researchers measured study participants' medical knowledge about mastectomy and mastectomy with reconstruction -- for example, effects of surgery on appearance and associated risks. They also measured individual preferences of what mattered most to patients. Key preference factors included breast appearance/shape post treatment, length of recovery time and risk for complications. "We found that less than half of the women had adequate medical knowledge about breast reconstruction and made a choice that aligned with their personal preferences. This is very concerning to us, because it means that some women did not get the treatment they truly preferred, and quite a few had more treatment than they preferred," says Clara Lee, MD, principal investigator of the study and a breast reconstructive surgeon at The OSUCCC - James. Lee holds a dual associate professor appointment in the colleges of medicine and public health at Ohio State. "Many women were quite concerned about complication risks, but they didn't actually know how high the risk was. This may explain some of the overtreatment that we saw," she adds. Researchers found that only 43 percent of the patients in the study demonstrated an understanding of at least half of the important facts about reconstruction and made a choice that was consistent with their preferences. Understanding of surgical complications was particularly low, with only 14 percent of patients demonstrating strong knowledge of associated risks. "As breast cancer providers, we need to talk about the pros and cons of surgery to help women make treatment choices. Shared decision-making between the surgeon and patient would be particularly useful for this decision. We need to connect patients with decision aids to help them really think through what is most important to them," Lee adds. Collaborators in this National Cancer Institute-funded study include Allison Deal, MD, and Ruth Huh, BA, of Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill; Michael Pignone, MD, MPH, of University of Texas at Austin; and Peter Ubel, MD, of Duke University. Lee and colleagues in Ohio State's colleges of engineering, communication and public health are working on a study to evaluate treatment decisions in early-stage breast cancer patients to assess how communication with their providers affects their decision-making. This ongoing study examines patients' knowledge, preferences, and expectations about future well-being. Information from this study is expected to help clinicians develop tools to aid patients in making an informed decision about their care. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 47 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. Learn more at cancer.osu.edu.


News Article | May 4, 2017
Site: www.eurekalert.org

Although the odds of developing breast cancer are nearly identical for black and white women, black women are 42 percent more likely to die from the disease. This mortality gap - driven by social and environmental, as well as biological factors - continues to persist. A large, multi-institutional study, published on-line May 4, 2017, in JAMA Oncology, was designed to understand this gap by beginning to unravel the germline genetic variations and tumor biological differences between black and white women with breast cancer. This is the first "ancestry-based comprehensive analysis of multiple platforms of genomic and proteomic data of its kind," the authors note. Findings from this study could lead to more personalized risk assessment for women of African heritage and hasten the development of novel approaches designed to diagnose specific subtypes of aggressive breast cancers early and treat them effectively. One new finding is that black women with hormone receptor positive, HER2-negative breast cancer had a higher risk-of-recurrence score than white women. The study also confirmed that black patients were typically diagnosed at a younger age and were more likely to develop aggressive breast-cancer subtypes, including basal-like or triple-negative cancers (tumors lacking estrogen receptors, progesterone receptors and HER2), as well as other aggressive tumor subtypes. "People have long associated breast cancer mortality in black women with poverty, or stress, or lack of access to care, but our results show that much of the increased risk for black women can be attributed to tumor biological differences, which are probably genetically determined," said study author Olufunmilayo Olopade, MD, professor of medicine and human genetics at the University of Chicago. "The good news," she said, "is that as we learn more about these genetic variations, we can combine that information with clinical data to stratify risk and better predict recurrences - especially for highly treatable cancers - and develop interventions to improve treatment outcomes." "This is a great example of how team science and investments in science can accelerate progress in identifying the best therapies for the most aggressive breast cancers," said co-author Charles Perou, PhD, a member of the University of North Carolina Lineberger Comprehensive Cancer Center and professor of genetics, and pathology & laboratory medicine at the UNC School of Medicine. "In the largest dataset to date that has good representation of tumors from black women, we did not find much difference between the somatic mutations driving tumors in black and white women," he added. "Yet black women were more likely to develop aggressive molecular subtypes of breast cancer. Now we provide data showing that differences in germline genetics may be responsible for up to 40 percent of the likelihood of developing one tumor subtype versus another." The study used DNA data collected from 930 women - 154 of predominantly African ancestry and 776 of European ancestry - available through The Cancer Genome Atlas (TCGA), established by the National Cancer Institute and the National Human Genome Research Institute. The researchers combed through the data methodically, looking for racial differences in germline variations (normal DNA), somatic mutations (tumor acquired), subtypes of breast cancers, survival time, as well as gene expression, protein expression and DNA methylation patterns. "Most significantly," explained first author Dezheng Huo, MD, PhD, associate professor of public health sciences at the University of Chicago, "we observed a higher genetic contribution to estrogen-receptor negative breast cancer in blacks." Black women were more likely to get these highly aggressive cancers. This is one of the first studies to connect genetics to this racial difference in tumor subtype frequencies. The study also revealed 142 genes that showed differences in expression levels according to race. One gene, CRYBB2 (Crystallin Beta B2), was consistently higher in tumors from black patients within each breast cancer subtype, as well as in normal tissues, suggesting it may be a race-specific gene. The researchers also found somatic mutations in 13 genes or DNA segments that differed in frequency in tumors from black and white women. One of them, a mutated gene called TP53, was more common in black women (52%) than white women (31%) and was a strong predictor of disease recurrence. "Despite the relatively short follow-up time in the TCGA dataset, we were able to detect a significant racial disparity in patient survival using breast cancer-free interval as the endpoint between patients of African and European ancestries," said co-first author Hai Hu, PhD, vice president for research at the Chan Soon-Shiong Institute of Molecular Medicine at Windber. "Most of the worst outcomes came from basal-like subtype breast cancer patients of African Ancestry." "Black women in all categories, including the most common breast cancers, were likely to have a worse prognosis," Olopade said. "Understanding the basic, underlying genetic differences between black and white women, the higher risk scores and the increased risk of recurrence should lead us to alternative treatment strategies," said Perou. The crucial long-term benefit of this study, according to Olopade, is that "it is a step toward the development of polygenic biomarkers, tools that can help us better understand each patient's prognosis and, as we learn more, play a role in choosing the best treatment." "Genes matter," she added. "This is a foot in the door for precision medicine, for scientifically targeted treatment." "This study now outlines a path for us to personalize breast cancer risk assessment and develop better strategies to empower all women, especially black women, to know their genetics and be more proactive in managing their risk," Perou said. The study was funded by the National Cancer Institute, the Breast Cancer Research Foundation, Susan G. Komen Foundation for the Cure, the American Cancer Society and the U.S. Department of Defense. Also contributing were Toshio Yoshimatsu and Jason Pitt from the University of Chicago; Katherine Hoadley and Melissa Troester of the University of North Carolina at Chapel Hill; Jianfang Liu, Yuanbin Ru, and Lori Sturtz from the Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA; Suhn Rhie of the University of Southern California; Eric Gamazon of Vanderbilt University; Andrew Cherniack from the Broad Institute of MIT and Harvard; Tara Lichtenberg from Nationwide Children's Hospital, Columbus, Ohio; Carl Shelly from the University of Wisconsin; Christopher Benz from the Buck Institute for Research on Aging, Novato, Calif.; Gordon Mill from The MD Anderson Cancer Center; Peter Laird from the Van Andel Research Institute, Grand Rapids, MI; and Craig D. Shriver from the Walter Reed National Military Medical Center, Bethesda, MD. To reach co-author Charles Perou, PhD, of the University of North Carolina Lineberger Comprehensive Cancer Center and professor of genetics, and pathology & laboratory medicine at the UNC School of Medicine, contact Laura Oleniacz, Science Communications Manager, UNC Lineberger Comprehensive Cancer Center, 919-445-4219, laura_oleniacz@med.unc.edu. To reach co-author Hai Hu, PhD, vice president for research at the Chan Soon-Shiong Institute of Molecular Medicine at Windber contact Natalie Bombatch, Communications & Marketing Manager, Chan Soon-Shiong Institute of Molecular Medicine, Windber, PA, 814-467-3447, nbombatch@windbercare.org.

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