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.”

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.

Tan et al. Opioid use among female breast cancer patients using different adjuvant endocrine therapy regimens. Breast Cancer Res Treat. 2017;165(2):455-465 [Abstract]

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Early deaths from childhood cancer up to 4 times more common than previously reported

Treatments for childhood cancers have improved to the point that 5-year survival rates are over 80 percent. However, one group has failed to benefit from these improvements, namely children who die so soon after diagnosis that they are not able to receive treatment, or who receive treatment so late in the course of their disease that it is destined to fail.

A study published in the Journal of Clinical Oncology explores this challenging population, finding that death within a month of diagnosis is more likely in very young children and those from minority racial and ethnic groups even independent of low socioeconomic status. The study uses a large national database to find that the rate of deaths within one month of diagnosis has been previously under-reported in clinical trial data, with early deaths from some pediatric cancer subtypes up to four times as common as had been implied by clinical trial reports.

During my pediatric residency a teenager came in with leukemia, but had so much cancer when he presented that he had multi-organ failure and died within about 24 hours of coming to our attention, before we could even start treatment. I wanted to find out who these kids are in hopes that as a system we could learn to spot them earlier, when treatment still has a chance of success,” says Adam Green, MD, investigator at the University of Colorado Cancer Center and pediatric oncologist at Children’s Hospital Colorado. Green originated this study during his clinical fellowship at Dana Farber Cancer Institute, working with Carlos Rodriguez Galindo, MD.

Green and colleagues used data from the Surveillance, Epidemiology and End Results (SEER) database, finding 36,337 cases of pediatric cancer between the years 1992 and 2011. Of these young patients, 555 or 1.5 percent died within one month of cancer diagnosis. Overall, the strongest predictor of patients who would die soon after diagnosis was age below one year.

In general, babies are just challenging, clinically, because they can’t tell you what they’re feeling. Parents and physicians have to pick the ones with cancer from the ones with a cold, without the patient being able to tell you about symptoms that could be diagnostic. Babies tend to get aggressive cancers, it’s hard to tell when they’re getting sick, and some are even born with cancers that have already progressed. These factors combine to make very young age the strongest predictor of early death in our study,” Green says.

Additionally, black race and Hispanic ethnicity predicted early death, even beyond the influence of socioeconomic status. Green hopes that future studies will be able to discover whether biologic or cultural factors may be responsible for these disparities, or if higher rates of early death in minority populations could be due to factors built into insurance and health care systems.

He also points out that the rate of early deaths due to pediatric cancers is higher than previously reported.

Most of what we know about outcomes for cancer patients come from clinical trials, which have much more thorough reporting rules than cancer treated outside trials. However, these kids in our study aren’t surviving long enough to join clinical trials,” Green says.

For example, the paper shows that a clinical trial against childhood Acute Myeloid Leukemia (AML) reported early death in 16 of 1,022 young patients, or 1.6 percent of these cases. In contrast, the SEER database, which collects about 15 percent of all cancer outcomes across the United States (representing a geographic and socioeconomic cross-section), shows 106 early deaths in 1,698 diagnoses, or 6.2 percent of all cases, almost four times as high as previously reported. When comparing the rates of early deaths seen in the SEER database to rates of early deaths reported in clinical trial data, early death was higher for all cancer subtypes (0.7 versus 1.3 percent in non-infant ALL; 2.0 versus 5.4 percent in infant ALL; 1.4 versus 3.8 percent in hepatoblastoma; 0.04 versus 0.5 percent in Wilms tumor).

I had a hunch this was a bigger problem than we thought. Now we see that is indeed the case,” says Green.

Now that Green has shown the fact of early death in this population, he hopes to work with CU Cancer Center colleagues to design a national prospective study that could more closely examine the factors associated with this outcome. “So that whenever a family has a child who dies of cancer within a month of diagnosis, we could contact the family to gather information about timing of symptoms and their experience accessing care. We can already act on our findings in this current study to improve early identification of these patients. But with prospective, patient-level data, we can move from understanding the scope and risk factors for early death to identifying problems in the diagnostic process we can fix,” Green explains.

The overall goal of this ongoing line of research is to change potential early deaths to long-term survivors.

This is a population that deserves our attention,” Green says.

Green et al.  Death Within 1 Month of Diagnosis in Childhood Cancer: An Analysis of Risk Factors and Scope of the Problem. Journal of Clinical Oncology (2017) DOI: 10.1200/JCO.2016.70.3249 [Article]

Cervical cancer death rates higher among older and black women

A woman’s risk of dying of cervical cancer is higher than long believed, particularly among older and black women, new Johns Hopkins Bloomberg School of Public Health-led research suggests.

The researchers found that black women in the United States are dying from cervical cancer at a rate 77 percent higher than previously thought while white women are dying at a rate 47 percent higher. The new figures reflect a change in how mortality rates are calculated. By excluding women who have had hysterectomies, which typically involves the removal of the cervix and therefore reduces the risk of developing cervical cancer to zero, the researchers say these data paint a more accurate picture of who is getting cervical cancer – and can be used to better understand how to prevent it.

Meanwhile, many of those who are dying are over the age of 65, a cutoff point where guidelines no longer recommend women with cervixes be regularly screened for cervical cancer. With routine screening, cervical cancer is preventable. In the United States, there are 12,000 cases of cervical cancer each year and around 4,000 deaths.

The findings, published Jan. 23 in the journal Cancer, highlight the need to understand the risks associated with cervical cancer in older and black women and determine both the best screening and treatment options for these women.

This is a preventable disease and women should not be getting it, let alone dying from it,” says study leader Anne F. Rositch, PhD, MSPH, an assistant professor in the Department of Epidemiology at the Bloomberg School. “Since the goal of a screening program is to ultimately reduce mortality from cervical cancer, then you must have accurate estimates within the population targeted by those programs — adult women with a cervix. These findings motivate us to better understand why, despite the wide availability of screening and treatment, older and black women are still dying from cervical cancer at such high rates in the United States.”

Excluding women with a history of a hysterectomy, something that has not been done in previous calculations, makes a sizable difference since one in five women in the United States have had a hysterectomy, with the number slightly higher in black women than white women. Current guidelines do not recommend cervical cancer screening after the age of 65, since it was believed that older women were at much less risk. These new findings suggest the risk remains – and even increases – in older women.

These data tell us that as long as a woman retains her cervix, it is important that she continue to obtain recommended screening for cervical cancer since the risk of death from the disease remains significant well into older age,” Rositch says.

To produce these national mortality rates, the researchers analyzed cervical cancer mortality rates using national death certificate data from the National Center for Health Statistics and from the Surveillance, Epidemiology, and End Results (SEER) national cancer registries and then removed the proportion of women who reported a hysterectomy, a number obtained from a national survey.

The rate of cervical cancer mortality among black women over the age of 20 was 5.7 per 100,000 each year and 3.2 per 100,000 each year in white women. The rate in black women jumped to 10.1 per 100,000 per year when corrected for hysterectomy, a rate similar to less developed nations, and to 4.7 per 100,000 per year in white women. Black women are more likely to have hysterectomies, and at younger ages, compared to white women, largely because black women are more susceptible to fibroids — benign masses in the uterus — which can cause symptoms requiring surgery. Including all women in mortality rate calculations underestimated the racial disparity in death rates between black and white women by 44 percent.

Current screening guidelines call for routine Pap smears to test for cervical cancer among women between 21 and 65. If women have had three healthy tests over the previous decade, they are no longer recommended for testing after the age of 65. An inexpensive Pap smear can find changes in the cervix before cancer develops. It can also find cervical cancer early, when it is in its most curable stage. Cervical cancer, which is caused by the human papillomavirus (HPV), can also be prevented by the HPV vaccine, which is offered to young people.

Rositch says it isn’t clear why older and black women are dying of cervical cancer at higher rates. Were they not properly screened? Was there no follow-up after an abnormal screening test? Was something missed during screening? Was treatment ineffective? Answering these questions are critical to identifying the most appropriate interventions that would lower these mortality rates.

Previous research suggests that black women are more likely to have their cervical cancer caught at a later stage of diagnosis and may receive different treatment than white women. One study found that black women had 50-percent lower odds of receiving surgery and 50-percent higher odds of receiving radiation compared to white women with the same stage and insurance.

While rare in the United States, cervical cancer is more common in the developing world. Worldwide, more than 500,000 women are diagnosed each year and more than 200,000 die. GLOBOCAN, an arm of the World Health Organization, estimated in 2012 that 9.8 women per 100,000 die of cervical cancer in less developed nations, including all of Africa, Asia (excluding Japan), Latin America and the Caribbean).

While trends over time show that the racial disparities gap has been closing somewhat, these data emphasize that it should remain a priority area,” Rositch says. “Black women are dying of cervical cancer at twice the rate as white women in the United States and we need to put in place measures to reverse the trend.”

Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States” was written by Anna Beavis, MD, MPH, Patti E. Gravitt, PhD, and Anne F. Rositch, PhD, MSPH. Collaborating institutions include the Johns Hopkins University School of Medicine and the George Washington University Milken Institute School of Public Health.

Beavis et al. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;doi:10.1002/cncr.30507 [Abstract]

Recovering Latina breast cancer patients report big gaps in ‘survivorship’ care

Breast cancer patients in one of the United States’ largest and fastest-growing ethnic minority groups are likely to experience numerous gaps in care following their primary treatment, research from Oregon State University suggests.

Seventy-four Latina women who had breast cancer participated in the “survivorship” care research, recruited through support groups and health fairs. The subjects, ages 30 to 75, took part in semi-structured focus groups that used a question guide crafted by a task force of academic researchers and community partners such as the American Cancer Society. Approximately half of the women were low-income, uninsured or publicly insured.

Results indicate numerous gaps and unmet needs in Latinas’ survivorship care experiences, including problems with finances, continuity of care, unmet needs for information, and symptom management,” said Carolyn Mendez-Luck, an assistant professor in OSU’s College of Public Health and Human Sciences and one of the authors of the study.

The California Breast Cancer Research Program provided primary funding for the research. Results were recently published in Public Health Nursing. Optimal survivorship care, according to the Institute of Medicine, includes the prevention of recurrence, new cancer and late effects of cancer treatment; the monitoring or surveillance for cancer and medical, mood and social issues; interventions for the effects of cancer and its treatment; and coordination among specialists and primary care providers to ensure all health needs are met.

Many survivors experience persisting symptoms including fatigue, pain, depression and sleep disturbance, but until recent years, survivorship has been relatively neglected in education, clinical practice and research,” Mendez-Luck said.

People of Mexican, Cuban, Puerto Rican, and Central and South American descent comprise 17.6 percent of the U.S. population, and about 10 percent of the women in the Hispanic/Latino population will develop breast cancer at some point in their lifetime.

Latina women are more likely to be diagnosed at later stages than non-Hispanic whites and also face linguistic and cultural barriers to diagnosis and treatment, including modesty; spiritual beliefs that cancer is God’s punishment; de-prioritizing their own health care in favor of their roles as mother and wife; and passivity in interactions with health care providers out of respect for their authority.

In addition, there are often financial hurdles – more than 25 percent of Latina women live in poverty and lack health insurance.

Understanding the cultural context in which women receive care is important,” Mendez-Luck said.
Women in the study sample expressed confusion and anxiety associated with a lack of information regarding future surveillance and treatment once primary care concluded. Many were unsure who was to be in charge of their treatment in the future, what the right schedule was for follow-up examinations, what self-care activities were recommended, and what to expect regarding their physical and psychological well-being.

Among the women in our focus groups, survivorship care plans were scarce,” Mendez-Luck said. “The vast majority of participants reported never having heard of them, or associated them with a completely different meaning – making a plan for how their families could carry on after they were gone.
The research also showed that depending on the person, “survivor” could have negative or positive connotations.

Negative perceptions included feelings that being identified as a cancer survivor was depressing, victimizing and stigmatizing,” Mendez-Luck said. “Also, that thinking about the cancer could potentially contribute to an increased likelihood of a recurrence, either by ‘tempting fate’ or from the stress brought on by negative thinking.

Positive views, the professor noted, included feeling special, strong, and blessed by God. Many survivors felt they had a special purpose for living, often including a mission to serve others.

A survivorship care plan is meant to be this living document for you and your care providers, a document a patient can follow through this entire process of what’s going on with the cancer and what she can do to stay healthy and reduce the chances that the cancer will return,” Mendez-Luck said. “It makes the patient truly a partner in her own care with health providers. But that’s not happening, clearly, at least not for these women. There’s an enormous opportunity there for improvement.

Tisnado et al. Perceptions of Survivorship Care among Latina Women with Breast Cancer in Los Angeles County. Public Health Nursing, 2016; DOI: 10.1111/phn.12299 [Abstract]

Combining new and old drugs improves survival for soft-tissue cancer patients

Adding a novel monoclonal antibody therapy to traditional chemotherapy increased median survival by nearly a year in patients with advanced sarcoma, a lethal soft-tissue cancer. Findings from a multicenter clinical trial of the combination therapy, led by researchers at Columbia University Medical Center and NewYork-Presbyterian, represent the first appreciable improvement in sarcoma outcomes in decades.

We estimated from preclinical data that the new drug–olaratumab–might improve survival in these patients by a few months, but the extent of the improvement exceeded everybody’s expectations,” said study leader Gary K. Schwartz, MD, professor of medicine at Columbia University Medical Center and chief of the division of hematology and oncology at NewYork-Presbyterian/Columbia. “While sarcoma remains a fatal disease, we’re encouraged that we’re on the right track and hope to build on this progress.”

Soft-tissue sarcomas are a group of cancers that arise in fat, muscle, nerves, joint linings, blood vessels, and other tissues that connect, support, and surround various body structures. There are more than 50 different types of soft-tissue sarcomas.

If caught early, sarcomas can be treated effectively with surgery. However, if the disease spreads, or metastasizes, treatment with chemotherapy does relatively little to slow disease progression or improve survival. The median survival time after diagnosis of advanced disease is 12 to 16 months. In 2015, 12,000 people were diagnosed with soft-tissue sarcomas and 5,000 died of the disease, according to the American Cancer Society.

Several years ago, Dr. Schwartz (then at Memorial Sloan Kettering Cancer Center) reported that a cell-surface receptor called platelet-derived growth factor receptor alpha (PDGFR-alpha)–found in many people with soft-tissue sarcoma–appeared to play a key role in tumor growth in specific sub-types of soft-tissue sarcoma. By inhibiting this receptor, he was able to get the sarcoma cells to stop growing in his laboratory.

Working in close association with scientists at ImClone, since acquired by Eli Lilly and Company, he developed the clinical trial with the agent olaratumab, a human monoclonal antibody that blocks PDGFR-alpha and disrupts this signaling pathway, which is critical for sarcoma growth. The drug was also shown to enhance the effects of a standard chemotherapy called doxorubicin, which is routinely used in the treatment of sarcoma. The study was published in The Lancet.In

In a phase 2 clinical trial, 133 patients with metastatic soft-tissue sarcoma were given either doxorubicin or doxorubicin plus olaratumab. The median overall survival of patients in the doxorubicin group was 14.7 months, compared to 26.5 months in the doxorubicin-olaratumab group. Adding olaratumab to standard chemotherapy did not significantly increase treatment side effects.

As an oncologist, I am ecstatic that the drug worked as well as it did,” said Dr. Schwartz. “As a physician-scientist, however, I remain frustrated because we still don’t know exactly why it worked as well as it did. It might be directly affecting the tumor cells, the tumor microenvironment (cells immediately around the tumor cells), or even the immune cells. The future development of this drug will be helped by figuring this out.”

Dr. Schwartz and his colleagues are currently studying other potential drug targets for arresting the progression of soft-tissue sarcomas. “Sarcomas are complex. There are, in fact, multiple receptors on the cell surface. PDGFR-alpha is just one of the receptors that are overexpressed on sarcoma cells. We now have some ideas about how to combine drugs that block multiple types of these receptors, which will probably be more effective that targeting a single type of receptor,” he said.

Eli Lilly recently completed a larger, phase 3 clinical trial of olaratumab, which included some of Dr. Schwartz’s patients at Columbia/NewYork-Presbyterian. Results of the study have not yet been published. In the meantime, the FDA has granted the drug priority review as a potential treatment for advanced soft-tissue sarcoma.

Tap et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 2016;http://dx.doi.org/10.1016/S0140-6736(16)30587-6 [Abstract]

Hispanic and black young adult cancer patients more likely to die of their disease

Hispanic white and non-Hispanic black cancer patients between ages 15 and 29 may be more likely than same-aged white patients to die of their disease, according to a University of Colorado Cancer Center study presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2016.

The finding is partially but not wholly explained by socioeconomic status, meaning that in addition to the health risks associated with low socioeconomic status or stage of presentation, there are additional health risks associated specifically with these racial/ethnic identities.

As with many disparities, you have to identify the problem before you can fix it,” says Meryl Colton, MS, medical student at University of Colorado School of Medicine, who performed the analysis with Adam L. Green, MD, investigator at the CU Cancer Center and pediatric oncologist at Children’s Hospital Colorado.

The study used data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) database to compare the overall rate of death in the two years following cancer diagnosis for the three above-mentioned racial/ethnic groups, as well as people with Medicaid or no insurance compared to private insurance. For example, taking the chance of a young-adult white patient dying within two years of being diagnosed with liver cancer as a baseline of “1”, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient’s chance of dying is 1.76.

“What this means is that black and Hispanic young adult patients are almost 75 percent more likely to die after being diagnosed with liver cancer than are white young adult patients,” Colton says.
This increased risk of mortality for black and Hispanic patients, as well as those without private health insurance, holds true across cancer types including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.

Much of this disparity is explained by the overlap between low socioeconomic status and racial/ethnic minority status, meaning that the increased chance of dying after a cancer diagnosis is due in part to conditions associated with having less financial resources no matter one’s race/ethnicity. However, even after controlling for insurance status, an indicator of socioeconomic status, and stage of presentation, disparities in death rates after cancer diagnosis remained between these racial/ethnic groups, implying an influence of race/ethnicity independent of financial resources.

This is a starting point,” says Colton. “Part of an analysis like this is saying, ‘hey, this exists!’ And now the second part is trying to figure out why this is happening.”

Though additional study is certainly required, Colton points to three possible components of this continuing disparity: The possibility that residual socioeconomic factors could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of these diseases to make cancers more dangerous in certain populations, or the possibility that the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.

This is a population that shouldn’t be getting cancer and it’s devastating when they do,” Colton says. “Knowing that a disparity exists allows us to ask questions that can help ensure everyone receives the best possible care.”

The American Society of Clinical Oncology (ASCO) annual meeting 2016, Chicago, Illinois

Can gender play a role in determining cancer treatment choices?

MD Anderson study reveals ‘sex-biased’ gene signatures in review of 13 cancer types
It is well known that men and women differ in terms of cancer susceptibility, survival and mortality, but exactly why this occurs at a molecular level has been poorly understood.

A study at The University of Texas MD Anderson Cancer Center reviewed 13 cancer types and provided a molecular understanding of sex effects in diverse cancers. The research revealed two cancer-type groups associated with cancer incidence and mortality, suggesting a “pressing need” to develop sex-specific therapeutic strategies for some cancers.The research findings are published online issue of Cancer Cell.

Using data from The Cancer Genome Atlas, a team led by Han Liang, Ph.D., associate professor of Bioinformatics and Computational Biology, found more than half of the genes studied that were related to clinical practice of cancer treatment showed sex-biased signatures in certain cancer types.

Our study helps elucidate the molecular basis for sex disparities in cancer and lays a critical foundation for the future development of precision cancer medicine that is sex-specific,” said Liang. “This is a crucial finding as currently, male and female patients with many cancer types often are treated in a similar way without explicitly considering their gender.

Liang’s group performed a comprehensive analysis of molecular differences between male and female patients, revealing two sex-effect groups associated with distinct incidence and mortality profiles and accounting for 53 percent of clinically actionable genes. Those genes are informative for clinical decisions and are either therapeutic targets or biomarkers that can help predict patient survival or tumor response.
In the study, Liang found one group contained a small number of sex-affected genes (weak group), while the other showed a much greater number of sex-biased molecular signatures (strong group). Liang said the current equal treatment of both genders may be appropriate for those in the “weak” group, but observations in the “strong” group are clinically significant.

Special consideration should be given to those in the strong sex-effect group in terms of both drug development and practice,” said Liang. “For a therapeutic target with a strong sex-biased signature, sex-specific clinical trials may be more likely to succeed. This new information is vital as the fundamental issue of sex differences for cancer prevention and therapy has not been investigated systematically.

Liang’s team analyzed data in patient cohorts of 30 or greater samples for each sex for various cancers of the bladder, colon, kidney, brain, rectum, thyroid, liver and lung as well as acute myeloid leukemia. They looked for specific molecular data including somatic mutations, copy alterations, protein and gene expression and DNA methylation. The study included controls for other factors such as race, age, disease stage, smoking status and tumor purity.

Interestingly, our analysis also suggested that sex bias might be amplified during the tumor formation process,” said Liang. “However this observation should be interpreted with caution at this early stage as further efforts are needed to determine the relative contributions of other factors, including tumorigenesis, sex chromosomes and hormones.”

Yuan et al. Comprehensive characterization of molecular differences in cancer between male and female patients. Cancer Cell, 2016;29:711–722 DOI: http://dx.doi.org/10.1016/j.ccell.2016.04.001 [Abstract]