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Breast Cancer Patients on Opioids Less Likely to Stick to Vital Treatment

A new study has found a troubling lack of adherence to a potentially lifesaving treatment regimen among breast cancer patients who take opioids to manage their pain.

The treatment, adjuvant endocrine therapy, commonly known as hormone therapy, is used to prevent the cancer from returning after surgery, chemotherapy or radiation therapy. Opioid use, however, was “significantly associated” with both failure to adhere to the hormone therapy and a higher risk of death, the study found.

Overall, the study found “really suboptimal” adherence to hormone therapy among the women on opioids, said researcher Rajesh Balkrishnan, PhD, of the University of Virginia School of Medicine’s Department of Public Health Sciences. “It’s not a big secret that the U.S. uses more opioids than any other country in the world,” he said. “Clearly there has to be better management of opioids in the elderly cancer population.”

One researcher cautioned that the opioid crisis sweeping the country may be causing doctors to become too cautious about prescribing the powerful drugs, even when appropriate and much needed. “A lot of doctors feel worried about prescribing them,” said researcher Leslie Blackhall, MD, a pain-management expert at the UVA Health System. “People feel judged for prescribing them.”

Appropriate Use of Opioids

Blackhall suggested that the lack of adherence to the adjuvant endocrine therapy, as seen in the study’s findings, may be due to the pain involved in the therapy, rather than because of the opioid use, as some might assume. The pain, she said, is why the patients need powerful opioids in the first place.

“The main problem is that these hormonal medications … have so many side effects that women do not want to take them. They can cause really severe joint and muscle pain in a significant number of women,” Blackhall said. “These women switch from one agent  to the other but still can't tolerate them. They are then given opioids for the pain, which may or may not help. The opioids may themselves add to the mortality, but we don't know. More data is needed.”

Breast Cancer and Opioids

Up to 60 percent of breast cancer survivors suffer chronic pain related to their treatment, the study notes. Survivors often face 10 years of adjuvant endocrine therapy to keep the cancer from coming back – a long time to comply with any treatment regimen, but especially if suffering poorly managed pain.

To better understand the relationship between opioid use and the hormone therapy, the researchers looked at treatment adherence among more than 10,000 women, with an average age of 72.3, using the National Cancer Institute’s expansive SEER database. They found that women who were younger, single and had more advanced cancer all were more likely to be on opioids, as were women with depression.

Women who received chemotherapy and breast cancer surgery were more likely to take opioids, but this was not the case for women receiving radiation therapy. This may be because of new, more targeted radiation therapy that causes less pain, the researchers hypothesized.

Using Opioids Safely

Researcher Virginia LeBaron, PhD, of the UVA School of Nursing, is a former medical oncology staff nurse and palliative care nurse practitioner. “These results underscore the importance of a balanced approach to the utilization of prescription opioid medications,” she said. “By balanced approach, I mean that it is critically important we ensure that prescription opioid medications are accessible to cancer patients who need them, but at the same time we must ensure we have appropriate systems in place to mitigate risk and reduce potential harms related to these medications.”

The researchers have published their findings in the scientific journal Breast Cancer Research and Treatment. Blackhall noted that the article is intended to foster dialogue and spur additional research. For example, clinical trials might compare opioids with non-opioids for managing cancer pain or identify patient subgroups that would most benefit from certain approaches to pain management.  “This study was really just a way to bring attention to the problem and the need to provide better care for patients,” she said.

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UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

Related items

  • Focused Ultrasound Shows Promise to Treat Parkinson’s Disease Tremor

    An initial test to determine if a scalpel-free form of brain surgery can reduce tremor caused by Parkinson’s disease has produced encouraging results. Further research is warranted, the researchers conclude in a paper published today by the scientific journal JAMA Neurology.

    The pilot study was led by Jeff Elias, MD, of the University of Virginia School of Medicine and also was conducted at Swedish Neuroscience Institute in Seattle. Twenty-seven participants with tremor-dominant Parkinson’s disease were enrolled in the study; the research team randomly assigned 20 to be treated with  focused ultrasound waves on their brains, while the seven others received a fake procedure, to account for any potential placebo effect. (They were later offered the opportunity to have the actual procedure). All had tremor that had resisted medical treatment, and all continued taking their existing Parkinson’s medication.

    The trial participants who received the focused ultrasound procedure had a 62 percent median improvement in their hand tremor three months later. Those who underwent a sham procedure also improved to a lesser degree, however, suggesting some placebo effect. Additional testing is needed to better establish the effectiveness of focused ultrasound for Parkinson’s tremor, the researchers concluded.

    The median age of trial participants was 67.8 years, and 26 were male. The most significant side effects reported were mild numbness on one side of the body, which improved, and numbness of the face and finger, which were persistent. Two subjects also experienced partial weakness that recovered or improved during the study. (The procedure has since been modified to mitigate this risk of weakness, the researchers say.)

    About Focused Ultrasound

    Focused ultrasound already has been approved by the U.S. Food and Drug Administration for the treatment of essential tremor, the most common movement disorder. That approval came after Elias and his colleagues at UVA pioneered the approach. Other researchers are also evaluating focused ultrasound’s potential for treating many other conditions, including breast cancer, brain tumors, epilepsy and pain.

    The technology works by focusing sound waves inside the body to generate a tiny hot spot, much like a magnifying glass focuses light. By carefully controlling this process, researchers can interrupt faulty brain circuits or destroy unwanted tissue. Unlike traditional brain surgery, there is no need to drill or cut into the skull. Magnetic resonance imaging lets the researchers monitor the location and intensity of the procedure in real time, an important safety feature when making permanent changes to the brain.

    Next Steps

    The researchers believe that a larger, multicenter study is needed to better define the potential role of focused ultrasound in managing Parkinson’s disease. 

    “Our findings suggest that the patients likely to benefit from this approach are those for whom tremor reduction is enough to improve their quality of life,” said UVA researcher Binit Shah, MD.

    To learn more about focused ultrasound at UVA, visit uvahealth.com/focusedultrasound. To keep up with all the latest developments and research breakthroughs from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu

    About the Parkinson’s Research

    The research team consisted of Aaron E. Bond, Shah, Diane S. Huss, Robert F. Dallapiazza, Amy Warren, Madaline B. Harrison, Scott A. Sperling, Xin-Qun Wang, Ryder Gwinn, Jennie Witt, Susie Ro and Elias.

    The research was supported by the Focused Ultrasound Foundation, the Commonwealth of Virginia, Diane and David Heller, Robert and Molly Hardie and the Prince Charitable Trust.

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    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Breastfeeding for 2 Months HALVES Risk of SIDS, Study Finds

    Breastfeeding for at least two months cuts a baby’s risk of Sudden Infant Death Syndrome almost in half, a sweeping new international study has found.

    The study determined that mothers do not need to breastfeed exclusively for their baby to get the benefit, potentially good news for moms who can’t or choose not to rely solely on breastfeeding.

    “These results are very powerful! Our study found that babies who are breastfed for at least two months have a significant reduction in their risk of dying from SIDS,” said researcher Kawai Tanabe, MPH, of the University of Virginia School of Medicine. “Breastfeeding is beneficial for so many reasons, and this is really an important one.”

    Preventing SIDS

    Previous studies have suggested that breastfeeding was associated with a decreased risk of SIDS, the leading cause of death of babies between 1 month and one year of age, but this study is the first to determine the duration necessary to provide that protection. The researchers found, after adjusting for variables that could distort their results, that breastfeeding for at least two months was associated with a significant decreased risk. Breastfeeding for less than two months did not offer such a benefit.

    “Breastfeeding for just two months reduces the risk of SIDS by almost half, and the longer babies are breastfed, the greater the protection,” said UVA researcher Fern Hauck, MD, of the UVA School of Medicine and the UVA Children's Hospital. “The other important finding from our study is that any amount of breastfeeding reduces the risk of SIDS — in other words, both partial and exclusive breastfeeding appear to provide the same benefit.”

    To determine the effects of breastfeeding on SIDS risk, the researchers analyzed eight major international studies that examined 2,259 cases of SIDS and 6,894 control infants where death did not occur. This large collective sample demonstrated the consistency of findings despite differing cultural behaviors across countries, and it provides convincing evidence of the reliability of the findings.

    Based on their results, the researchers are calling for “ongoing concerted efforts” to increase rates of breastfeeding around the world. Data from 2007 showed that a quarter of U.S. babies had never been breastfed, the researchers report. (The World Health Organization has established a goal of having more than half of infants worldwide being breastfed exclusively for at least six months by 2025.)

    “It’s great for mothers to know that breastfeeding for at least two months provides such a strong protective effect against SIDS,” said researcher Rachel Moon, MD, of the UVA School of Medicine and the UVA Children's Hospital. “We strongly support international and national efforts to promote breastfeeding.”

    It remains unclear why breastfeeding protects against SIDS, though the researchers cite factors such immune benefits and effects on infant sleeping patterns as possible mechanisms.

    Findings Published

    The researchers have published their findings in the scientific journal Pediatrics. The research team consisted of John M.D. Thompson, of New Zealand’s University of Auckland; Kawai Tanabe of the UVA School of Medicine; Rachel Y. Moon, of the UVA School of Medicine; Edwin A. Mitchell, of the University of Auckland; Cliona McGarvey, of Temple Street Children’s University Hospital in Dublin, Ireland; David Tappin, of the University of Glasgow’s School of Medicine in Scotland; Peter S. Blair, of the School of Social and Community Medicine at the University of Bristol in England; and Fern R. Hauck, of the UVA School of Medicine.

    To keep up with the latest medical research news from UVA, subscribe to the  blog at http://makingofmedicine.virginia.edu.

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    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Aetna introduces new Medicare Advantage plan with UVA Health System

    Aetna (NYSE: AET) today announced a new Aetna Medicare Advantage plan with a $29 monthly plan premium. This plan is available for Medicare beneficiaries in Charlottesville as well as Albemarle, Fluvanna, Greene, Louisa, Madison and Nelson counties. The Aetna Medicare UVA Health System Prime Plan provides access to University of Virginia Health System’s network, physicians and other health care providers at in-network rates.

    Enrolled Medicare Advantage patients will experience more coordinated care. They’ll benefit from improved information flow to the UVA physicians providing care. This is particularly helpful for patients with chronic or complex health needs. Aetna nurse case managers will assist UVA care providers with care coordination, outreach and follow-up services.

    Plan highlights include a $0 copay for primary care physician office visits, lab services and routine vision and eye exams, along with $0 medical and pharmacy annual deductibles.

    “Aetna is pleased to offer Medicare beneficiaries a new low-premium plan that focuses on collaboration and quality of care,” said Mike Bucci, president of Aetna’s operations in Virginia. “We will work closely with the doctors and health care professionals at UVA Health System to provide each member with a personalized and coordinated health care experience.”

    “This relationship will help us better provide patient-centered care that is focused on health and wellness to Medicare beneficiaries throughout the Charlottesville region by helping us enhance care coordination,” said Pamela M. Sutton-Wallace, chief executive officer of UVA Medical Center.

    This plan will be available in Charlottesville as well as Albemarle, Fluvanna, Greene, Louisa, Madison and Nelson counties during the Medicare Annual Enrollment Period this fall with an effective date of January 1, 2018.

    For more information about the plan, please visit www.AetnaMedicare.com/UVA.

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    About Aetna

    Aetna is one of the nation’s leading diversified health care benefits companies, serving an estimated 44.7 million people with information and resources to help them make better informed decisions about their health care. Aetna offers a broad range of traditional, voluntary and consumer-directed health insurance products and related services, including medical, pharmacy, dental, behavioral health, group life and disability plans, and medical management capabilities, Medicaid health care management services, workers’ compensation administrative services and health information technology products and services. Aetna’s customers include employer groups, individuals, college students, part-time and hourly workers, health plans, health care providers, governmental units, government-sponsored plans, labor groups and expatriates. For more information, see www.aetna.com and learn about how Aetna is helping to build a healthier world@AetnaNews

    Aetna Medicare is a PDP, HMO, PPO plan with a Medicare contract. Our SNPs also have contracts with State Medicaid programs. Enrollment in our plans depends on contract renewal. This information is not a complete description of benefits. Contact the plan for more information. Limitations, copayments, and restrictions may apply. Benefits and/or co-payments/co-insurance may change on January 1 of each year. Other providers are available in our network. You must continue to pay your Medicare Part B premium. See Evidence of Coverage for a complete description of plan benefits, exclusions, limitations and conditions of coverage. Plan features and availability may vary by service area.

    About UVA Health System

    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

  • Exercise Discovery Could Save Lives of Sickest, Most Gravely Injured

    A new discovery about how exercise helps protect us from disease could one day dramatically reduce the death rate among the sickest and most gravely injured.

    People suffering from severe trauma or the full-body infection known as sepsis often develop multiple organ dysfunction syndrome, or MODS. It’s as though the immune system turns against the patient, attacking the vital organs instead of the infection. MODS is a primary cause of death in intensive care units, killing up to 80 percent of patients who develop it. Frustratingly, doctors know little about why it occurs, and nothing can be done to stop it. But the new discovery from the University of Virginia School of Medicine could change that.

    “This data suggests if everything is true, if this can indeed provide protection against sepsis and multi-organ dysfunction, that would imply that 80 percent of deaths in the clinical ICU could be cut in half,” said UVA researcher Zhen Yan, PhD.

    Exercise for Disease Prevention

    Yan’s research in mice suggests that skeletal muscles naturally make an antioxidant that helps get rid of excessive free radicals, unstable atoms that can damage cells. The antioxidant, known as EcSOD, is one of the mechanisms by which exercise protects the body from disease, his findings show. “This data really provides direct evidence that a humoral factor, a factor carried in the blood circulation produced by the largest organ of the body, ‘knows’ intelligently where to go and really provides protection where there is crisis,” said Yan, of UVA’s Department of Medicine and UVA’s Robert M. Berne Cardiovascular Research Center.  

    The antioxidant helps prevent MODS by protecting the first line of defense, the vessel wall, and preventing inflammatory cells from accumulating inside the vital organs. “In the condition of sepsis and severe trauma, our defense system becomes exaggerated to the point that [the body’s immune defenses] misunderstand the signal, so that they begin to attack the organs,” Yan said. “Our body is mistakenly thinking there is a danger signal coming from the organs themselves.”

    The new insight into the role of this elegant antioxidant that is produced by our body may let doctors rein in the excessive and damaging immune response. “If we understand the mechanism, we may be able to strategically and intelligently design better pharmacological interventions and genetic interventions,” Yan said.

    “Clinically, this has huge implications, indicating the importance of regular exercise in keeping us more resistant to many disease conditions,” he noted. “Even under the condition of serious disease, like sepsis, you have a better chance to survive.”

    Benefits for Patients, Troops

    Yan, a top expert in the study of the benefits of exercise, said his findings may offer a way to head off MODS and sepsis if those conditions are caught early. It’s unclear if a treatment based on the finding would help those with severe multi-organ dysfunction, he said. But he can foresee another benefit as well: “It could have tremendous implications for personnel deployed to the battlefield who may get injured,” he said. “If we train them regularly with the appropriate exercise regimen which will produce more [of the antioxidant] from the muscle, or we can design ways to provide biologically active EcSOD to subjects who are either vulnerable or who have already started to have severe disease conditions, this may lead to a huge impact on their survival.”

    Findings Published

    The researchers have published their findings online in the scientific journal Free Radical Biology & Medicine. The paper was authored by Jarrod A. Call, Jean Donet, Kyle S. Martin, Ashish K. Sharma, Xiaobin Chen, Jiuzhi Zhang, Jie Cai, Carolina A. Galarreta, Mitsuharu Okutsu, Zhongmin Du, Vitor A. Lira, Mei Zhang, Borna Mehrad, Brian H. Annex, Alexander L. Klibanov, Russell P. Bowler, Victor E. Laubach, Shayn M. Peirce and Yan.

    The work was supported by the National Institutes of Health, grant R01GM109473, and the American Heart Association.

    To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

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    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Susan G. Komen Awards UVA $450,000 for Innovative Breast Cancer Research

    Researcher Melanie Rutkowski, PhD, can envision a day when doctors prescribe a specific diet to prevent the spread of breast cancer. A day when doctors could identify women at high risk for breast tumors just by examining the bacteria in their guts.

    And now Susan G. Komen has awarded her $450,000 to fund pioneering research that could make that happen.

    Over the next three years, the grant will let Rutkowski, of the University of Virginia School of Medicine, expand our understanding of the relationship between the microbiome – the microorganisms that naturally live in our bodies – and the immune system’s response to breast cancer. She will seek to determine if chronic disruption of the microbiome, possibly caused by diets heavy in processed foods, fats and sugar, is hurting the immune system’s ability to battle breast tumors – and perhaps even facilitating the cancer’s spread through the body.

    “One of the underlying questions about breast cancer is why do some individuals with breast cancer develop more aggressive or metastatic disease? And why is there so much variability in the context of how their immune systems respond to these cancers?” said Rutkowski, of the UVA Cancer Centerand UVA’s Carter Immunology Center. “What our research is suggesting is that these microbes that live within us, when they are unbalanced, they can dramatically influence disease progression, making the tumors more aggressive and ultimately result in the inability of the immune system to eliminate the tumor.”

    Breast Cancer’s Link to the Gut

    Doctors are increasingly realizing the importance of the microbiome in human health and disease, Rutkowski noted. “It’s becoming more and more appreciated now that these microbes are involved in a whole variety of different pathologies,” she said. “There have been links with neurological disorders, with certain metabolic disorders, and now there’s a lot of appreciation of how these microbes, especially within the gastrointestinal tract, influence the immune response against certain types of cancer.”

    Once breast cancer has spread, it is untreatable, so preventing its spread – known as metastasis – is vital. Rutkowski’s research suggests that manipulating the microbiome may lead to better outcomes. It could be as simple as a doctor instructing a patient to eat a diet high in fiber to complement her treatment regimen, Rutkowski said.

    “These microorganisms have many functions. They provide a first line of defense against invading pathogens, they are involved in aiding in digestion, they have a lot of metabolic products that they secrete that help to break down the food we ingest,” she said. “Those metabolic products actually have immune regulatory activity. They help to maintain the balance of good inflammation and bad inflammation, and what is becoming really appreciated about these microorganisms is that they are able to influence our immune system. Our interest, then, is to understand how they influence cancer.”

    That understanding could then be put to use in the war against breast cancer – leading to better treatments and better ways to identify women at risk, Rutkowski hopes. “Ultimately,” she said, “I’d like to see this work benefit patients.”

    About Susan G. Komen

    Susan G. Komen has invested more than $920 million to support pioneering research around the world since its founding in 1982. The group is committed to supporting research, people and resources that will reduce breast cancer deaths in the United States by 50 percent by 2026.

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    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

    About UVA Cancer Center
    UVA Cancer Center is accredited by the Commission on Cancer and is one of 69 National Cancer Institute (NCI) designated cancer centers in the U.S. for its work in cancer research, prevention, detection and treatment. UVA Cancer Center provides comprehensive, world-class cancer treatment in an environment of caring for patients across Virginia, led by doctors who have been honored by publications such as Best Doctors in America® and America’s Top Doctors®.

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