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ABIRATERONE EFFECTIVE ALSO IN HIGH GLEAN SCORE PROSTATE CANCER

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In 1,048 prostate cancer patients previously treated with docetaxel, and 996 metastatic, castration-resistant patients, treatment with the androgen-lowering drug abiraterone acetate (Zytiga) led to longer overall disease control, even when a very high Gleason score indicated especially aggressive cancer.
Study Findings
Results recently published by Fizazi et al in the Annals of Oncology show that for patients with Gleason score greater than 8, postdocetaxel treatment with abiraterone extended progression-free survival from 5.5 months to 6.4 months, and prechemotherapy abiraterone treatment extended progression-free survival from 8.2 months to 16.5 months.
“We have the idea that with an unfavorable Gleason score, we have to immediately reach for the harshest chemicals, but this study shows that's not always the case. Abiraterone is easier to take, has fewer side effects, and shows prolonged survival,” said Thomas Flaig, MD, Associate Director for Clinical Research at the University of Colorado Cancer Center, and Associate Professor of Medicine at the University of Colorado School of Medicine.
Dr. Flaig was coinvestigator of clinical trials that led to U.S. Food and Drug Administration (FDA) approval of abiraterone acetate, and with collaborators, continues to explore the best use of the drug. Previous work showed that the drug is useful even in cases of prostate cancer that has metastasized to the liver, another poor prognostic sign. The current study extends this finding to include all aggressive prostate cancers marked by high Gleason score.
“The main thing this analysis does is help us better understand how to use this new agent. Certainly there are cases in which cytotoxic chemotherapies are appropriate. But this study points to a broad use of this oral hormonal agent,” Dr. Flaig said.
In addition to extending the duration of progression-free survival, this study showed greater overall survival and better control of prostate-specific antigen with abiraterone treatment. The treatment is used in combination with prednisone.
“Thus, the Gleason score at the time of diagnosis should not factor into the decision to prescribe or treat a patient with metastatic castration-resistant prostate cancer with abiraterone acetate plus prednisone,” the authors concluded.

FACTS FOR BREAST CANCER SCREENING

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Findings of a systematic review of the benefits and harms of breast cancer screening commissioned by the American Cancer Society (ACS) to inform its updated guideline on screening in average-risk women were reported in JAMAby Myers et al of the Duke Evidence Synthesis Group. Their findings were published along with the updated ACS guideline.
The review included literature searches through March 2014, yielding 7 reviews, 10 randomized clinical trials, 72 observational studies, and 1 modeling study providing relevant data. Key findings of the systematic review are reproduced here.
Key Findings
  • Across all ages of women at average risk, pooled estimates of the association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials: relative risk (RR) = 0.80, 95% confidence interval [CI] = 0.73–0.89, in a UK Independent Panel analysis; RR = 0.82, 95% CI = 0.74–0.94, in a Canadian Task Force analysis; and RR = 0.81, 95% CI = 0.74–0.87, in a Cochrane analysis.
  • Risk reduction was greater in a meta-analysis of cohort studies (RR = 0.75, 95% CI = 0.69–0.81) and similar in a modeling study (Cancer Intervention and Surveillance Modeling Network; median RR equivalent among seven models = 0.85 (range = 0.77–0.93).
  • There is uncertainty about the magnitude of screening-associated mortality reduction in the entire U.S. population, among women aged 40 to 49 years, and with annual vs biennial screening.
  • There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to a lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis.
  • For women with a first mammography screening at age 40 years, the estimated 10-year cumulative risk of a false-positive biopsy result was higher with annual (7.0%, 95% CI = 6.1%–7.8%) than biennial screening (4.8%, 95% CI = 4.4%–5.2%). Ten-year probabilities of false-positive biopsy results were similar among women first screened at age 50 years, but indirect estimates of lifetime probability of false-positive results were lower.
  • Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was of low quality.
  • There was no direct evidence for any additional mortality benefit associated with the addition of clinical breast examination to mammography. Observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of clinical breast exam.
The investigators concluded: “For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.”
The study was funded by the American Cancer Society.

SURGERY FOR METASTATIC BREAST CANCER ?

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The overall survival of patients who are initially diagnosed with metastatic breast cancer has improved by 6 months over the past 2 decades, according to a population-based study conducted in the United States.
And the improvement is associated with breast surgery after the initial diagnosis, which is a debated practice in these patients, according to the authors, led by Mary Schroeder, PhD, a health services researcher at the University of Iowa in Iowa City.
The investigators reviewed data on 21,372 metastatic patients from the Surveillance, Epidemiology, and End Results (SEER) program for two periods — 1988 to 1991 and 2007 to 2011. They found that median survival increased from 20 months in the earlier period to 26 months in the later period.
None of the patients received radiation therapy as part of their first course of treatment, and only 39% underwent surgery.
Nevertheless, surgery was found to be associated with better survival on multivariate analysis that controlled for patient characteristics, clinical characteristics, and time period (hazard ratio, 0.60; 95% confidence interval [CI], 0.57 - 0.63).
The study, which was published online today in JAMA Surgery, provides a "contemporary" look at these patients, the investigators say.
"This updates earlier reports, which described outcomes for women diagnosed as having stage IV breast cancer more than a decade ago," they explain.
So does the study suggest that patients diagnosed with metastatic breast cancer should undergo surgery?
Not necessarily, according to the investigators.
Surgery might provide "critical disease control" for some patients and "could be" a component of prolonged survival, they conclude.
But they acknowledge that surgery might be a "surrogate" for other factors that extend life but are not reviewable in the SEER data, such as systemic therapies, social support, and access to care.
Randomized clinical trials and prospective patient registries are needed to truly define the observed survival benefit seen in this study, Dr Schroeder and her colleagues note.
In fact, a randomized trial being conducted in Canada and the United States (ECOG E2108) has recently completed accrual, and a Japanese trial is nearing completion, Dr Schroeder told Medscape Medical News.
In the meantime, what should clinicians and patients do?
"I offer breast surgery selectively to patients with stage IV disease," said Lisa A. Newman, MD, MPH, director of the breast oncology program at the Henry Ford Health System in Detroit.
The goals of surgery include the reduction of the "total body burden of disease," Dr Newman, who also wrote an accompanying editorial, told Medscape Medical News.
Patients who are "more likely" to benefit in this way are "medically fit with limited distant organ involvement and with disease that is amenable to targeted endocrine and/or anti-HER2/neu therapy," she said.
But other patients might also benefit. "Evidence of metastatic focus downstaging in response to primary systemic therapy would be another feature indicating possible benefit," Dr Newman added.
And patients with "bulky, ulcerated, or fungating breast tumors represent a distinctly different scenario, where surgery might be considered purely for palliation," she added.
Metastatic patients "often" want surgery, Dr Schroeder explained. However, "most commonly," surgery is not recommended by their multidisciplinary teams.
Two recent phase 3 trials comparing surgery with no surgery in metastatic breast cancer have shown no survival benefit with surgery, Dr Newman reports in her editorial.
However, both of these studies were international, and might not be relevant in a "more affluent country such as the United States, where patients have improved access to advanced diagnostic and treatment options," she said. For example, the trial conducted in India did not include anti-HER2/neu therapy, as reported by Medscape Medical News in 2013.
If surgery does indeed improve survival, it is probably a modest benefit, Dr Schroeder and her colleagues contend.
"A large benefit for many women with stage IV breast cancer with surgery to the intact primary tumor is unlikely, especially as an ever-increasing array of more potent and targeted drugs may be able to provide better control or even eradication of systemic disease," they write.
However, their results suggest that the benefit could be long term, which is the hoped-for outcome for all metastatic cancers.
Of the 7504 patients diagnosed with metastatic disease before 2002, survival of at least 10 years was seen in 353 patients who underwent surgery and in 107 who did not (9.6% vs 2.9%; odds ratio [OR], 3.61; 95% CI, 2.89 - 4.50).
On multivariate analysis, survival of at least 10 years was associated with receipt of surgery (OR, 2.80; 95% CI, 2.08 - 3.77). Surgery was a more powerful predictor of this long-term survival than age, tumor size, year of diagnosis, marital status, race/ethnicity, or tumor receptor status, the investigators report.
This study was supported in part by the University of Iowa Holden Comprehensive Cancer Center Population Research Core, which is supported in part by a National Cancer Institute grant. The study authors and Dr Newman have disclosed no relevant financial relationships.


ANTHRACYCLINE USE LINKED TO LONG TERM MEMORY PROBLEMS?

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Anthracyclines might increase the risk for certain long-term memory problems and brain injury in patients with breast cancer, according to a small study published online December 3 in JAMA Oncology.
The study is the first to directly assess the neurotoxic effects of anthracyclines and nonanthracyclines in long-term survivors of breast cancer.
Cognitive problems related to cancer and its treatment are sometimes referred to as "cancer brain." These problems can persist over the long term and greatly decrease quality of life. Studies have linked chemotherapy to faster brain aging and to neurodegenerative disorders like Alzheimer's disease.
So far, the neurotoxic effects of various types of chemotherapy regimens are unclear, say researchers Shelli Kesler, PhD, from the University of Texas M.D. Anderson Cancer Center in Houston, and Douglas W. Blayney, MD, from the Stanford University School of Medicine in Palo Alto, California.
But their study indicates that regimen matters.
"Using standardized neuropsychological tests and resting state fMRI, we demonstrated significantly lower verbal memory performance and left precuneus connectivity in participants who received anthracycline regimens compared with those who received nonanthracycline regimens and to participants who did not receive chemotherapy," the pair write.
The left precuneus region is involved in memory, visuospacial processing, and consciousness. It is part of the brain's default mode network, which refers to cognitive activities carried out while the brain is at rest. Changes in connectivity in this region could lower the efficiency of information processing. Past studies have suggested that the default mode network is particularly vulnerable to the chemotherapy used to treat breast cancer. Studies have also linked changes in the default mode network to neurodegenerative disorders, Drs Kesler and Blayney report.
In their study, the researchers evaluated results from standardized cognitive tests and resting state functional MRI data for 62 survivors of primary breast cancer (mean age, 54.7 years). Patients had been off therapy for an average of 2 years. Twenty patients had received four to eight cycles of anthracycline-based chemotherapy, 19 had received four to eight cycles of nonanthracycline chemotherapy, and 23 had no history of chemotherapy. Patients were treated at Stanford University from 2008 to 2014.
There was a significant decrease in verbal memory performance in the anthracycline group, compared with the other two groups. This included a decrease in immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001).
There was also less left precuneus connectivity in the anthracycline group than in the other two groups (F = 7.48; P = .001). And patients treated with anthracyclines had significantly less default mode network connectivity (effect size, 0.6 - 1.3; P = .001).
Patient-reported outcomes for cognitive dysfunction and psychologic distress were worse in patients treated with anthracyclines (F = 7.27; P = .002) and nonanthracyclines (F = 5.64; P = .006) than in those not treated with chemotherapy. Executive functioning and fatigue were also worse in both chemotherapy groups than in the no-chemotherapy group.
There was no association between the number of chemotherapy cycles and cognitive status (P > .50), or between the number of cycles and treatment with endocrine therapy (P > .63). Adjustment for disease stage did not significantly change the results.
The small sample size and the retrospective cross-sectional design limited the study, the researchers acknowledge.
"Larger, prospective studies are needed that include pretreatment and post-treatment assessments so that patients' individual cognitive and neurobiologic trajectories can be evaluated with respect to potential anthracycline-related neurotoxic effects," the researchers conclude. "Continued research regarding the mechanisms by which anthracyclines disrupt neurocircuitry could help identify interventions that will protect against anthracycline-associated neurotoxic effects without reducing the anticancer efficacy of these regimens."
The complexity of research in this area was highlighted in an accompanying editorial by Kelly Nudelman, PhD, Brenna McDonald, PsyD, and Andrew Saykin, PsyD, all from the Indiana University School of Medicine in Indianapolis.
Imaging studies have suggested that a wide array of brain regions are affected by cancer and chemotherapy, they write. "Connectomics," they suggest, could help create a larger picture of the way cancer and its treatment affect cognitive functioning and brain networking.
Larger studies need to include different types of cancer, evaluate genetic factors, and look at the differential role of various cancer agents in neurodegeneration and cognitive aging, they explain.
"Additional prospective studies are needed to address baseline differences and the impact of specific treatments on cognitive function, the underlying neural substrate, and specific biological pathways," the editorialists write. "Resolving the pathways leading to cognitive dysfunction will be important for development of targeted interventions."
Dr Kesler and her colleagues note that anthracyclines, such as doxorubicin, work by inducing double-stranded DNA breaks and free-radical damage in both healthy and cancerous cells. The use of these agents has been linked to neuroinflammation, oxidative stress, and cerebrovascular disease, such as microinfarcts, all of which could contribute to neurodegeneration.

NINTEDANIB FAILED IN OVARIAN CANCER

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NEW YORK (Reuters Health) - In a phase III trial, women with advanced ovarian cancer had a small improvement in progression-free survival with nintedanib, but at the expense of gastrointestinal side effects, according to European investigators.
Nintedanib is an oral inhibitor of the VEGF receptors (VEGFRs) 1-3, fibroblast growth factor receptors (FGFRs) 1-3, and platelet-derived growth factor receptors (PDGFRs) alpha and beta, with anti-angiogenic activity.
"The trial supports the concept that angiogenesis is a valuable target in ovarian cancer," wrote Dr. Andreas du Bois, in an email to Reuters Health. At this point, however, it's not clear whether the company will try to register the drug for ovarian cancer, he said. It is approved for lung cancer treatment.
In a paper online November 15 in Lancet Oncology, Dr. du Bois of Oslo University Hospital in Norway and colleagues reported on 1,366 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IV ovarian cancer and upfront debulking who were randomly assigned to receive standard carboplatin and paclitaxel chemotherapy protocols with or without nintedanib.
Nine study groups in 22 countries participated.
Median progression-free survival was about two weeks longer with nintedanib vs placebo (17.2 vs 16.6 months; p=0.024).
"There will be another analysis focusing on overall survival," Dr. du Bois told Reuters Health. "It is not mature yet."
Post hoc analyses revealed that women with low postoperative tumor burden saw the largest benefit in progression-free survival. In this non-high-risk subgroup, median progression-free survival was 27.1 months with nintedanib, compared to 20.8 months with placebo.
Gastrointestinal side effects occurred in 21% in the nintedanib group vs 2% in the placebo group.
Rates of grade 3 and grade 4 neutropenia were 20% and 22%, respectively, with nintedanib and 20% and 16% with placebo.
Serious adverse events occurred in 42% of the nintedanib group and 34% of the placebo group. The rate of adverse events leading to death were 3% with nintedanib and 4% with placebo.
The high rate of adverse GI events "demands more attention and needs further optimization," Dr. du Bois said. "However, the rate of patients stopping the drug completely was not so high, indicating that dose modifications and pauses may be an appropriate way to improve tolerability."
Dr. Charles Drescher of the Fred Hutchinson Cancer Research Center at the University of Washington in Seattle, who was not involved in the research, told Reuters Health, "Similar to prior trials, it is demonstrating some activity for anti-angiogenesis effect. However, the effectiveness is pretty modest and not a huge impact."
He added: "You have to balance that against the GI toxicity and the cost of the drug."
In a comment published with the paper, Dr. Sean Kehoe from the Institute of Cancer and Genomics at the University of Birmingham, UK, points to the "intriguing" finding that "women at lower risk of progression or lower postsurgical tumor burden who were in the nintedanib group had a longer median progression-free survival."
Dr. Kehoe contrasts this with findings from the ICON7 trial of bevacizumab added to upfront therapy, in which women with larger tumor burden or stage IV disease had improved overall survival.
"Besides the different drugs used, how can this difference be explained?" Dr. Kehoe asks. He suggests, as does Dr. du Bois, that patients with stage IV cancer in ICON7 might have been reclassified in this trial as low-risk after tumor clearance.
The study was funded by Boehringer Ingelheim.
SOURCE: http://bit.ly/1MRD51Q
Lancet Oncol 2015.

NEW GENOMIC TEST INCREASES BRONCOSCOPY SENSITIVITY

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A new genomic test may be able to improve the diagnostic performance of bronchoscopy and help avoid the need for more invasive procedures in patients with suspected lung cancer.
"This test can change clinical practice in pulmonary medicine," commented senior author Avrum Spira, MD, professor of medicine at Boston University School of Medicine, in Massachusetts, who is the coinventor of the test. "It allows physicians to confidently identify patients who are at low probability for having lung cancer following an indeterminate bronchoscopy result."
The Percepta Bronchial Genomic Classifier (Veracyte) is a bronchial-airway gene-expression classifier. Results of two large studies show that this genomic test can help pinpoint which patients with suspicious lung lesions may be able to safely avoid lung biopsies.
The results of both studies were presented at the American Thoracic Society 2015 International Conference, being held in Denver, Colorado, and were published concurrently online in the New England Journal of Medicine.
With the advent of the use of low-dose CT in the screening of patients at high risk for lung cancer, more suspicious lesions are being detected. The next step for these patients is a bronchoscopy. Following these two procedures, patients are then assessed as being at high, intermediate, or low risk for cancer. "The sweet spot for the test," Dr Spira told Medscape Medical News, "is the intermediate-risk group."
"While the test did well across all groups, the most difficult cases are where the physician is not sure what the next step is," he said.
Low-risk patients may just need to be followed closely and have repeat scans, whereas a biopsy would be indicated for high-risk patients. But for patients at intermediate risk, it is not as clear, Dr Spira explained. "And this is the group where the test had the biggest impact in clinical decision making. It had a negative predictive value of 91%, and these results provide an opportunity for patients to be monitored using CT scans instead of having to go undergo biopsy."
Accurate Diagnosis of Cancer
The test is a 23-gene molecular classifier that can detect molecular changes in the epithelial cells that line the respiratory tract. Cells are obtained from cytology brushings taken during bronchoscopy from the proximal airway.
Dr Spira and colleagues undertook the two studies to prospectively validate this classifier in patients undergoing bronchoscopy for suspected lung cancer and also to evaluate whether its use could change the diagnostic performance of bronchoscopy.
The cohort included current or former smokers who were undergoing bronchoscopy for suspected lung cancer at 28 different centers. A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A genomic analysis was conducted in epithelial cells that were collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer.
In AEGIS-1, the classifier accurately identified 194 of 220 patients with cancer (sensitivity, 88%; 95% confidence interval [CI], 83 to 92) and 37 of 78 patients without cancer (specificity, 47%; 95% CI, 37 to 58).
For the AEGIS-2 study, results were similar. The classifier correctly identified 237 of 267 patients with cancer (sensitivity, 89%; 95% CI, 84 to 92) and 35 of 74 patients without the disease.
In patients with a nondiagnostic bronchoscopic examination, the classifier accurately identified cancer in 49 of 57 patients in AEGIS-1 (sensitivity, 86%; 95% CI, 74 to 94) and in 58 of 63 patients in AEGIS-2 (sensitivity, 92%; 95% CI, 82 to 97).
False Negatives
Although the classifier achieved a high negative predictive value in patients with a nondiagnostic bronchoscopic examination, the authors note that 13 patients in this group had a false negative result. Although they had lung cancer, they had a negative classifier score. The majority of them (10 of 13) had a high (>60%) probability of cancer; three patients had an intermediate (10% to 60%) pretest probability of cancer.
There are going to be some false negatives, Dr Spira pointed out. "But the patients are followed and will have repeat scans."
The test is already on the market, but the initial release was limited to only about 30 centers through an early access program, he said. "It was a soft launch, and will soon be more readily available."
It can be performed in any facility in which bronchoscopies are performed. Samples are sent to a central laboratory to be analyzed.
The study is funded by Allegro Diagnostics and by grants from the National Institutes of Health, the Department of Defense, and the National Cancer Institute. Dr Spira is a coinventor of the genomic test; several of the authors have listed potential conflicts of interest, including relationships with Allegro.

STUDY FINDS LINK BETWEEN TESTICULAR CANCER AND GYM SUPPLEMENTS

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Men who reported taking muscle-building supplements, such as pills and powders with creatine or androstenedione, reported a significantly higher likelihood of having developed testicular cancer than men who did not use such supplements, according to a study by Li et al in the British Journal of Cancer.
Moreover, said study senior author Tongzhang Zheng, DSc, the associated testicular germ cell cancer risk was especially high among men who started using supplements before age 25, those who used multiple supplements, and those who used them for years.
“The observed relationship was strong,” said Dr. Zheng, who led the study at Yale University School of Public Health, before joining the Brown University School of Public Health as Professor of Epidemiology. “If you used [supplements] at [an] earlier age, you had a higher risk. If you used them longer, you had a higher risk. If you used multiple types, you had a higher risk.”
Increasing Incidence of Testicular Cancer
Testicular cancer incidence rose to 5.9 cases per 100,000 men in 2011, from 3.7 cases in 100,000 in 1975, Dr. Zheng said. Researchers aren't sure why.
“Testicular cancer is a very mysterious cancer,” he said. “None of the factors we've suspected can explain the increase.”
The study is the first analytical epidemiologic study of the possible link between supplements and testicular cancer. Research was inspired by mounting evidence that at least some supplement ingredients may damage the testes.
“Our study found that supplement use was related to a higher risk of developing testicular cancer. These results are important, because there are few identified modifiable risk factors for testicular cancer,” said Russ Hauser, MD, MPH, ScD, Professor of Environmental Health Science at Harvard T.H. Chan School of Public Health.
Study Finds Significant Risk
Dr. Zheng's research team conducted detailed interviews of nearly 900 men from Massachusetts and Connecticut—356 of whom had been diagnosed with testicular germ cell cancer, and 513 who had not. In the interviews, researchers asked the men not only about their supplement use, but also about a wide variety of other possible factors, such as smoking, drinking, exercise habits, family history of testicular cancer, and prior injury to the testes or groin.
After tallying their data and accounting for all possible confounders, as well as age, race, and other demographics, the researchers found that men who used supplements had a 1.65 odds ratio (a 65% greater risk) of having developed testicular cancer compared to the men who did not use supplements.
The researchers defined “use” as consuming one or more supplements at least once a week for four consecutive weeks or more.
The odds ratios increased to 2.77 (a 177% greater risk) among men who used more than one kind of supplement, and to 2.56 among men who used supplements for 3 years or longer. Men who started using supplements at age 25 or younger also had an elevated associated odds ratio of 2.21, the researchers calculated.
“Considering the magnitude of the association and the observed dose-response trends, muscle-building supplement use may be an important and modifiable exposure that could have important scientific and clinical importance for preventing testicular germ cell cancer development, if this association is confirmed by future studies,” the study authors concluded.
Future large epidemiologic studies and laboratory experiments would be necessary to establish a causal link between supplements and testicular cancer.
Dr. Zheng is the corresponding author for the British Journal of Cancer article.
The study was supported by the National Institutes of Health, the National Natural Science Foundation of China, The Beijing Natural Science Foundation, and the Beijing Nova Program.

STATINS INCREASE DIABETES RISK

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Statin therapy appears to increase the risk for type 2 diabetes by 46%, even after adjustment for confounding factors, a large new population-based study concludes.
This suggests a higher risk for diabetes with statins in the general population than has previously been reported, which has been in the region of a 10% to 22% increased risk, report the researchers, led by Henna Cederberg, MD, PhD, from the University of Eastern Finland and Kuopio University Hospital, and colleagues, who published their study online March 4 in Diabetologia.
The majority of people in this new study were taking atorvastatin and simvastatin, and the risk for diabetes was dose-dependent for these two agents, the researchers found.
Nevertheless, senior author Markku Laakso, MD, from the University of Eastern Finland and Kuopio University Hospital, told Medscape Medical News: "Even if statin treatment is increasing the risk of getting diabetes, statins are very effective in reducing cardiovascular risk.
"Therefore I wouldn't make a conclusion from my study that people should stop statin treatment, especially those patients who have a history of myocardial infarction or so on.
"But what I would say is that people who are at the higher risk, if they are obese, if they have diabetes in the family, etc, should try to lower their statin dose, if possible, because high-dose statin treatment increases the risk vs lower-dose statin treatment," he continued.
Asked to comment, Alvin C Powers, MD, from Vanderbilt University School of Medicine, Nashville, Tennessee, explained that there were limitations to the conclusions that could be drawn from this study.
Speaking as part of the Endocrine Society, he said: "The first thing is that this study did not examine the benefits of statin therapy, it examined only the risk of diabetes."
With every treatment, there are risks and benefits, and the benefits of statins have been clearly proven in certain situations. In those instances, "the benefit would outweigh the increased risk of diabetes for many people," Dr Powers told Medscape Medical News.
Statins Appear to Affect Insulin Secretion and Sensitivity 
Dr Cederberg and colleagues explain that previous studies have suggested an increased risk of developing diabetes, of varying levels, associated with statin use. However, in many of these, study populations have been selective, especially in statin trials, which have included participants at high risk for cardiovascular disease.
Hence, the risk for diabetes in clinical trials is likely to differ from that in the general population. And very often, in previous studies the diagnosis of diabetes has been based on self-reported diabetes or fasting glucose measurement, leading to an underestimation of the actual numbers of incident diabetes cases.
In this new study, the authors investigated the effects of statin treatment on blood glucose control and the risk for type 2 diabetes in 8749 nondiabetic men age 45 to 73 years in a 6-year follow-up of the population-based  Metabolic Syndrome in Men (METSIM) trial, based in Kuopio, Finland.
The authors also investigated the mechanisms of statin-induced diabetes by evaluating changes in insulin resistance and insulin secretion.
Diabetes was diagnosed via an oral glucose tolerance test (OGTT), HbA1c levels ≥ 6.5% (48 mmol/mol) or by having started glucose-lowering medication. During the follow-up, 625 of the participants were diagnosed with diabetes. OGTT-derived indices were used to assess insulin sensitivity and secretion.
Statins were taken by 2412 individuals. The drugs were associated with an increased risk for type 2 diabetes even after adjustment for age, body mass index, waist circumference, physical activity, smoking, alcohol intake, family history of diabetes, and beta-blocker and diuretic treatment, at a hazard ratio (HR) of 1.46.
The risk was found to be dose-dependent for simvastatin and atorvastatin, which were taken by 388 and 1409 participants, respectively. High-dose simvastatin was associated with a hazard ratio (HR) of 1.44 for diabetes vs 1.28 for low-dose therapy, while the HR for diabetes with high-dose atorvastatin was 1.37.
Statin therapy was also associated with a significant increase in 2-hour glucose (= .001) and the glucose area under the curve at follow-up (  < .001), as well as a nominally significant increase in fasting plasma glucose (= .037).
Furthermore, individuals taking statins had a 24% decrease in insulin sensitivity and a 12% reduction in insulin secretion compared with those not receiving the drugs. These increases were again dose-dependent for atorvastatin and simvastatin.
Although pravastatin, fluvastatin, and lovastatin were found to be less diabetogenic than atorvastatin and simvastatin, the number of participants taking these agents was too small to reliably estimate their individual effects on the risk for diabetes, the research team notes.
Which Patients Should Take Statins?
Discussing the take-home message for prescribers seeking to balance the risk for diabetes with the benefits of statin therapy, Dr Laasko reiterated that individuals with a history of cardiovascular events and high LDL cholesterol "should definitely take statins."
However, he emphasized that the main aim of statins is to prevent a recurrent cardiovascular event, so individuals need to have had one event to start statin therapy.
"But in primary prevention, especially in women, who are at a lower risk of getting cardiovascular disease, maybe we should be more careful when we start statin treatment?" he ventured. "Statins are not meant to be a treatment for everybody."
Dr Powers observed that this new study doesn't provide any information about whether people who have diabetes who are on a statin should continue with the statin, "but there are clear benefits for statin therapy in people who have diabetes.
"People who have diabetes who are on a statin should continue with the statin.…This increased risk of diabetes, to me, is not relevant to their reason for taking the statin," he commented.
And in diabetes patients who have heart disease and are taking a statin, "the risk/benefit ratio would clearly be in the direction of benefit," Dr Powers observed.
In individuals who do not have diabetes and who are taking a statin, for example to reduce their risk for cardiovascular disease, "statin therapy has to be considered in the context of what's the benefit of the statin therapy in that group…especially in individuals who are genetically susceptible to type 2 diabetes or who have prediabetes," he continued.
"Those individuals will need to be monitored for the development of diabetes."
"People who are taking statins should keep taking statins, if there's an appropriate reason for them taking a statin. The risk/benefit ratio in most people is in favor of benefit; the risk is outweighed by that benefit," he concluded.
This work has been supported by the Academy of Finland, the Finnish Diabetes Research Foundation, the Finnish Cardiovascular Research Foundation, the Strategic Research Funding from the University of Eastern Finland, Kuopio, and a grant from Kuopio University Hospital. The authors have reported no relevant financial relationships.

NEW GENOMIC TEST INCREASES BRONCOSCOPY SENSITIVITY

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A new genomic test may be able to improve the diagnostic performance of bronchoscopy and help avoid the need for more invasive procedures in patients with suspected lung cancer.
"This test can change clinical practice in pulmonary medicine," commented senior author Avrum Spira, MD, professor of medicine at Boston University School of Medicine, in Massachusetts, who is the coinventor of the test. "It allows physicians to confidently identify patients who are at low probability for having lung cancer following an indeterminate bronchoscopy result."
The Percepta Bronchial Genomic Classifier (Veracyte) is a bronchial-airway gene-expression classifier. Results of two large studies show that this genomic test can help pinpoint which patients with suspicious lung lesions may be able to safely avoid lung biopsies.
The results of both studies were presented at the American Thoracic Society 2015 International Conference, being held in Denver, Colorado, and were published concurrently online in the New England Journal of Medicine.
With the advent of the use of low-dose CT in the screening of patients at high risk for lung cancer, more suspicious lesions are being detected. The next step for these patients is a bronchoscopy. Following these two procedures, patients are then assessed as being at high, intermediate, or low risk for cancer. "The sweet spot for the test," Dr Spira told Medscape Medical News, "is the intermediate-risk group."
"While the test did well across all groups, the most difficult cases are where the physician is not sure what the next step is," he said.
Low-risk patients may just need to be followed closely and have repeat scans, whereas a biopsy would be indicated for high-risk patients. But for patients at intermediate risk, it is not as clear, Dr Spira explained. "And this is the group where the test had the biggest impact in clinical decision making. It had a negative predictive value of 91%, and these results provide an opportunity for patients to be monitored using CT scans instead of having to go undergo biopsy."
Accurate Diagnosis of Cancer
The test is a 23-gene molecular classifier that can detect molecular changes in the epithelial cells that line the respiratory tract. Cells are obtained from cytology brushings taken during bronchoscopy from the proximal airway.
Dr Spira and colleagues undertook the two studies to prospectively validate this classifier in patients undergoing bronchoscopy for suspected lung cancer and also to evaluate whether its use could change the diagnostic performance of bronchoscopy.
The cohort included current or former smokers who were undergoing bronchoscopy for suspected lung cancer at 28 different centers. A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A genomic analysis was conducted in epithelial cells that were collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer.
In AEGIS-1, the classifier accurately identified 194 of 220 patients with cancer (sensitivity, 88%; 95% confidence interval [CI], 83 to 92) and 37 of 78 patients without cancer (specificity, 47%; 95% CI, 37 to 58).
For the AEGIS-2 study, results were similar. The classifier correctly identified 237 of 267 patients with cancer (sensitivity, 89%; 95% CI, 84 to 92) and 35 of 74 patients without the disease.
In patients with a nondiagnostic bronchoscopic examination, the classifier accurately identified cancer in 49 of 57 patients in AEGIS-1 (sensitivity, 86%; 95% CI, 74 to 94) and in 58 of 63 patients in AEGIS-2 (sensitivity, 92%; 95% CI, 82 to 97).
False Negatives
Although the classifier achieved a high negative predictive value in patients with a nondiagnostic bronchoscopic examination, the authors note that 13 patients in this group had a false negative result. Although they had lung cancer, they had a negative classifier score. The majority of them (10 of 13) had a high (>60%) probability of cancer; three patients had an intermediate (10% to 60%) pretest probability of cancer.
There are going to be some false negatives, Dr Spira pointed out. "But the patients are followed and will have repeat scans."
The test is already on the market, but the initial release was limited to only about 30 centers through an early access program, he said. "It was a soft launch, and will soon be more readily available."
It can be performed in any facility in which bronchoscopies are performed. Samples are sent to a central laboratory to be analyzed.
The study is funded by Allegro Diagnostics and by grants from the National Institutes of Health, the Department of Defense, and the National Cancer Institute. Dr Spira is a coinventor of the genomic test; several of the authors have listed potential conflicts of interest, including relationships with Allegro.

CARDIAC MONITORING DURING TRASTUZUMAB TREATMENT

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Breast cancer patients on adjuvant trastuzumab need cardiac monitoring, but most don't get it, new research suggests.
"We suspected that the rates of cardiac monitoring were going to be low, but we were surprised at how low the rates were, particularly in this high-risk group of patients. Of particular concern was that, even among patients with cardiac comorbidities, the rates of cardiac monitoring were not higher," lead author Dr. Mariana Chavez-MacGregor, assistant professor of Cancer Prevention at the University of Texas MD Anderson Cancer Center in Houston, told Reuters Health by email.
Physician characteristics may have greater influence than patient factors on the adequacy of cardiac monitoring, the authors wrote online May 11 in the Journal of Clinical Oncology.
Dr. Chavez-MacGregor and colleagues extracted Medicare-linked data from the Surveillance, Epidemiology, and End Results (SEER) database and the Texas Cancer Registry (TCR) to examine the patterns and adequacy of cardiac monitoring and to evaluate factors associated with adequate monitoring.
According to the authors, "Cardiac monitoring with echocardiogram or radionuclide ventriculography (multiple-gated acquisition scans) is part of the standard of care among patients receiving trastuzumab-based chemotherapy. The National Comprehensive Cancer Network guidelines recommend cardiac monitoring at baseline and at 3, 6, and 9 months after initiating trastuzumab therapy."
They identified 2,203 patients age 66 or older, with a median age of 72, who had full Medicare coverage and had been diagnosed with stage I to III breast cancer between 2005 and 2009 and treated with trastuzumab.
Only 793 (36.0%) of the patients were adequately monitored.
Patients who received optimal cardiac monitoring were more likely to have a more recent year of diagnosis (hazard ratio 1.83), a physician graduating after 1990 (HR, 1.66), a female prescribing physician (HR 1.37), and anthracycline use (HR 1.39).
Patients with cardiac comorbidities were not more likely to receive adequate cardiac monitoring.
Overall, 15.3% of the variance in the adequacy of cardiac monitoring was attributable to physician factors and 5.2% to patient factors.
"I think that our findings can create awareness among oncologists and hopefully impact the practice of oncologists by improving the rates of cardiac monitoring," Dr. Chavez-MacGregor wrote in an email.
Dr. Tracey O'Connor, associate professor of oncology at Roswell Park Cancer Institute in Buffalo, New York, told Reuters Health by email, "At 36%, the rates of optimal cardiac monitoring in this interesting study were surprisingly low, given the ready availability of guidelines to shape medical practice, and the knowledge that older patients are particularly likely to develop cardiac toxicity, making monitoring critical."
"Cardiac monitoring is especially important in elderly patients, who have more preceding cardiac history and are at higher risk for developing cardiac problems from trastuzumab," advised Dr. O'Connor, who was not involved in the study.
Dr. Susmita Parashar, director of the Winship at Emory Cardio-Oncology Program of Emory University in Atlanta, Georgia, said by phone, "These findings that only about one-third of these patients received adequate monitoring are alarming. It is disappointing that the quality of care is so low, but it does not surprise me because in a similar study, we found that only about one-third of lymphoma patients had adequate cardiac monitoring."
"Breast cancer patients taking trastuzumab may have decreased ejection fraction. If we don't follow up with these patients, they may have heart failure," cautioned Dr. Parashar, who was not involved in the study.
"Early detection and monitoring can prevent further progression. It's very important to monitor these patients so we can detect early subclinical heart disease and prevent heart failure," she added.
The authors acknowledged that they were limited by the retrospective nature of the data and the characteristics inherent in claims-based research.
Dr. Chavez-MacGregor called for further research "to determine what is the optimal/needed time interval to perform tests and whether any other tests (echocardiogram with strain for example) might be better to detect early cardiac dysfunction.
Dr. Chavez-MacGregor has received financial support from Roche, the parent company of Genentech, the maker of Herceptin (trastuzumab).