User login
Tic disorders are associated with obesity and diabetes
The movement disorders are associated with cardiometabolic problems “even after taking into account a number of covariates and shared familial confounders and excluding relevant psychiatric comorbidities,” the researchers wrote. “The results highlight the importance of carefully monitoring cardiometabolic health in patients with Tourette syndrome or chronic tic disorder across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder (ADHD).”
Gustaf Brander, a researcher in the department of clinical neuroscience at Karolinska Institutet in Stockholm, and his colleagues conducted a longitudinal population-based cohort study of individuals living in Sweden between Jan. 1, 1973, and Dec. 31, 2013. The researchers assessed outcomes for patients with previously validated diagnoses of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. Main outcomes included obesity, dyslipidemia, hypertension, T2DM, and cardiovascular diseases, including ischemic heart diseases, arrhythmia, cerebrovascular diseases, transient ischemic attack, and arteriosclerosis. In addition, the researchers identified families with full siblings discordant for Tourette syndrome or chronic tic disorder.
Of the more than 14 million individuals in the cohort, 7,804 (76.4% male; median age at first diagnosis, 13.3 years) had a diagnosis of Tourette syndrome or chronic tic disorder in specialist care. Furthermore, the cohort included 5,141 families with full siblings who were discordant for these disorders.
Individuals with Tourette syndrome or chronic tic disorder had a higher risk for any metabolic or cardiovascular disorder, compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99) and sibling controls (aHR, 1.37). Specifically, individuals with Tourette syndrome or chronic tic disorder had higher risks for obesity (aHR, 2.76), T2DM(aHR, 1.67), and circulatory system diseases (aHR, 1.76).
The increased risk of any cardiometabolic disorder was significantly greater for males than it was for females (aHRs, 2.13 vs. 1.79), as was the risk of obesity (aHRs, 3.24 vs. 1.97).
The increased risk for cardiometabolic disorders in this patient population was evident by age 8 years. Exclusion of those patients with comorbid ADHD reduced but did not eliminate the risk (aHR, 1.52). The exclusion of other comorbidities did not significantly affect the results. Among patients with Tourette syndrome or chronic tic disorder, those who had received antipsychotic treatment for more than 1 year were significantly less likely to have metabolic and cardiovascular disorders, compared with patients not taking antipsychotic medication. This association may be related to “greater medical vigilance” and “should not be taken as evidence that antipsychotics are free from cardiometabolic adverse effects,” the authors noted.
The study was supported by a research grant from Tourettes Action. In addition, authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.
SOURCE: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.
The movement disorders are associated with cardiometabolic problems “even after taking into account a number of covariates and shared familial confounders and excluding relevant psychiatric comorbidities,” the researchers wrote. “The results highlight the importance of carefully monitoring cardiometabolic health in patients with Tourette syndrome or chronic tic disorder across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder (ADHD).”
Gustaf Brander, a researcher in the department of clinical neuroscience at Karolinska Institutet in Stockholm, and his colleagues conducted a longitudinal population-based cohort study of individuals living in Sweden between Jan. 1, 1973, and Dec. 31, 2013. The researchers assessed outcomes for patients with previously validated diagnoses of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. Main outcomes included obesity, dyslipidemia, hypertension, T2DM, and cardiovascular diseases, including ischemic heart diseases, arrhythmia, cerebrovascular diseases, transient ischemic attack, and arteriosclerosis. In addition, the researchers identified families with full siblings discordant for Tourette syndrome or chronic tic disorder.
Of the more than 14 million individuals in the cohort, 7,804 (76.4% male; median age at first diagnosis, 13.3 years) had a diagnosis of Tourette syndrome or chronic tic disorder in specialist care. Furthermore, the cohort included 5,141 families with full siblings who were discordant for these disorders.
Individuals with Tourette syndrome or chronic tic disorder had a higher risk for any metabolic or cardiovascular disorder, compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99) and sibling controls (aHR, 1.37). Specifically, individuals with Tourette syndrome or chronic tic disorder had higher risks for obesity (aHR, 2.76), T2DM(aHR, 1.67), and circulatory system diseases (aHR, 1.76).
The increased risk of any cardiometabolic disorder was significantly greater for males than it was for females (aHRs, 2.13 vs. 1.79), as was the risk of obesity (aHRs, 3.24 vs. 1.97).
The increased risk for cardiometabolic disorders in this patient population was evident by age 8 years. Exclusion of those patients with comorbid ADHD reduced but did not eliminate the risk (aHR, 1.52). The exclusion of other comorbidities did not significantly affect the results. Among patients with Tourette syndrome or chronic tic disorder, those who had received antipsychotic treatment for more than 1 year were significantly less likely to have metabolic and cardiovascular disorders, compared with patients not taking antipsychotic medication. This association may be related to “greater medical vigilance” and “should not be taken as evidence that antipsychotics are free from cardiometabolic adverse effects,” the authors noted.
The study was supported by a research grant from Tourettes Action. In addition, authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.
SOURCE: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.
The movement disorders are associated with cardiometabolic problems “even after taking into account a number of covariates and shared familial confounders and excluding relevant psychiatric comorbidities,” the researchers wrote. “The results highlight the importance of carefully monitoring cardiometabolic health in patients with Tourette syndrome or chronic tic disorder across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder (ADHD).”
Gustaf Brander, a researcher in the department of clinical neuroscience at Karolinska Institutet in Stockholm, and his colleagues conducted a longitudinal population-based cohort study of individuals living in Sweden between Jan. 1, 1973, and Dec. 31, 2013. The researchers assessed outcomes for patients with previously validated diagnoses of Tourette syndrome or chronic tic disorder in the Swedish National Patient Register. Main outcomes included obesity, dyslipidemia, hypertension, T2DM, and cardiovascular diseases, including ischemic heart diseases, arrhythmia, cerebrovascular diseases, transient ischemic attack, and arteriosclerosis. In addition, the researchers identified families with full siblings discordant for Tourette syndrome or chronic tic disorder.
Of the more than 14 million individuals in the cohort, 7,804 (76.4% male; median age at first diagnosis, 13.3 years) had a diagnosis of Tourette syndrome or chronic tic disorder in specialist care. Furthermore, the cohort included 5,141 families with full siblings who were discordant for these disorders.
Individuals with Tourette syndrome or chronic tic disorder had a higher risk for any metabolic or cardiovascular disorder, compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99) and sibling controls (aHR, 1.37). Specifically, individuals with Tourette syndrome or chronic tic disorder had higher risks for obesity (aHR, 2.76), T2DM(aHR, 1.67), and circulatory system diseases (aHR, 1.76).
The increased risk of any cardiometabolic disorder was significantly greater for males than it was for females (aHRs, 2.13 vs. 1.79), as was the risk of obesity (aHRs, 3.24 vs. 1.97).
The increased risk for cardiometabolic disorders in this patient population was evident by age 8 years. Exclusion of those patients with comorbid ADHD reduced but did not eliminate the risk (aHR, 1.52). The exclusion of other comorbidities did not significantly affect the results. Among patients with Tourette syndrome or chronic tic disorder, those who had received antipsychotic treatment for more than 1 year were significantly less likely to have metabolic and cardiovascular disorders, compared with patients not taking antipsychotic medication. This association may be related to “greater medical vigilance” and “should not be taken as evidence that antipsychotics are free from cardiometabolic adverse effects,” the authors noted.
The study was supported by a research grant from Tourettes Action. In addition, authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.
SOURCE: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.
FROM JAMA NEUROLOGY
Key clinical point: Monitor cardiometabolic health in patients with Tourette syndrome or chronic tic disorder.
Major finding: Patients with Tourette syndrome or chronic tic disorder have a higher risk of metabolic or cardiovascular disorders, compared with the general population (adjusted hazard ratio, 1.99) and sibling controls (adjusted hazard ratio, 1.37).
Study details: A Swedish longitudinal, population-based cohort study of 7,804 individuals with Tourette syndrome or chronic tic disorder.
Disclosures: The study was supported by a research grant from Tourettes Action. Authors reported support from the Swedish Research Council and a Karolinska Institutet PhD stipend. Two authors disclosed personal fees from publishers, and one author disclosed grants and other funding from Shire.
Source: Brander G et al. JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4279.
Soy didn’t up all-cause mortality in breast cancer survivors
A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.
The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.
Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.
The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.
Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.
There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.
However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.
This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”
Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho
Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.
Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.
The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.
Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.
Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.
Patient, disease, and treatment characteristics did not differ significantly among the tertiles.
An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.
For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.
For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).
Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).
Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”
“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”
The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”
The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.
The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
SOURCE: Ho S et al. NAMS 2018, Abstract S-23.
A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.
The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.
Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.
The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.
Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.
There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.
However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.
This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”
Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho
Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.
Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.
The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.
Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.
Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.
Patient, disease, and treatment characteristics did not differ significantly among the tertiles.
An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.
For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.
For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).
Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).
Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”
“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”
The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”
The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.
The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
SOURCE: Ho S et al. NAMS 2018, Abstract S-23.
A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.
The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.
Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.
The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.
Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.
There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.
However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.
This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”
Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho
Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.
Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.
The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.
Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.
Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.
Patient, disease, and treatment characteristics did not differ significantly among the tertiles.
An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.
For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.
For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).
Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).
Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”
“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”
The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”
The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.
The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
SOURCE: Ho S et al. NAMS 2018, Abstract S-23.
REPORTING FROM NAMS 2018
Key clinical point: Soy consumption did not increase mortality risk in breast cancer survivors.
Major finding: The hazard ratios for all-cause mortality were 0.63 and 0.95 for the two highest tertiles of soy consumption.
Study details: An ongoing prospective cohort study of 1,497 female breast cancer survivors in Hong Kong.
Disclosures: The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
Source: Ho S et al. NAMS 2018, Abstract S-23.
Daily News Special: SABCS
Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Neoadjuvant degarelix more effective than triptorelin for ovarian suppression
Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.
Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.
Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.
Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.
“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the Journal of Clinical Oncology.
Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.
All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.
The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.
One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.
The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.
There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.
The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.
SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.
Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.
Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.
Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.
Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.
“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the Journal of Clinical Oncology.
Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.
All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.
The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.
One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.
The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.
There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.
The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.
SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.
Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than a GnRH agonist in achieving ovarian function suppression in women with breast cancer, results of a randomized trial show.
Ovarian function suppression was achieved more rapidly and maintained more effectively with degarelix, compared with triptorelin, in the premenopausal women who were receiving letrozole for neoadjuvant endocrine therapy, investigators said.
Adverse events including hot flashes and injection site reactions were reported more often with degarelix versus the GnRH agonist in this randomized, phase 2 trial of 51 subjects.
Additional research is needed to determine whether degarelix results in superior disease control versus the current standard of care, reported Silvia Dellapasqua, MD, of the European Institute of Oncology IRCCS in Milan, Italy, and coinvestigators.
“The study is hypothesis-generating, and supports later studies to assess whether maintenance of ovarian function suppression with degarelix translates into a better clinical outcome and is worth a trade-off of increased rate of some adverse events,” the researchers wrote. The report is in the Journal of Clinical Oncology.
Patients were randomly assigned to receive degarelix plus letrozole or triptorelin plus letrozole for six 28-day cycles. Degarelix was administered subcutaneously on day 1 of each cycle, while triptorelin was administered intramuscularly on day 1 of each cycle, and oral letrozole was to be taken daily. Surgery was performed a few weeks after the last injection.
All patients achieved optimal ovarian function suppression by the end of the first cycle. However, that endpoint was achieved significantly faster among patients in the degarelix arm, at a median of 3 days, versus a median of 14 days for the GnRH agonist, the investigators reported.
The optimal ovarian function suppression was seen three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than 001), they added.
One hundred percent of patients receiving degarelix and letrozole maintained optimal ovarian function suppression throughout the study, while about 15% of patients assigned to triptorelin had suboptimal suppression after that first cycle.
The group of patients receiving degarelix had a higher rate of node-negative disease at surgery, and a higher rate of breast-conserving surgery compared with the triptorelin group, the investigators said.
There were two grade 3 adverse events, hypertension and anemia, which both occurred in the triptorelin group, and no grade 4 adverse events. The most common adverse events reported were hot flashes, occurring in 80.0% and 69.2% of the degarelix and triptorelin groups, respectively; arthralgias in 32.0% and 53.8%; insomnia in 24.0% and 11.5%; injection site reactions in 24.0% and 0%; and nausea in 16.0% and 3.8%.
The study was supported by Ferring, and by the International Breast Cancer Study Group via Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland, Oncosuisse, Swiss Cancer League, and the Foundation for Clinical Cancer Research of Eastern Switzerland. The authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.
SOURCE: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Degarelix, the gonadotropin-releasing hormone (GnRH) antagonist approved for prostate cancer, was more effective than the GnRH agonist triptorelin in achieving ovarian function suppression.
Major finding: Ovarian function suppression occurred three times faster with degarelix (hazard ratio, 3.05; 95% confidence interval, 1.65-5.65; P less than .001) and in contrast to the triptorelin group, none had suboptimal suppression on subsequent cycles.
Study details: A randomized phase 2 trial including 51 premenopausal women receiving letrozole for locally advanced, endocrine-responsive breast cancer.
Disclosures: The study was supported in part by Ferring. Authors reported disclosures related to Ferring, Novartis, Ipsen, DVAX, Roche, Genentech, Pfizer, Celgene, and Merck, among others.
Source: Dellapasqua S et al. J Clin Oncol. 2018 Dec 27. doi: 10.1200/JCO.18.00296.
As deep sleep decreases, Alzheimer’s pathology – particularly tau – increases
The protein was evident in areas associated with memory consolidation, typically affected in Alzheimer’s disease: the entorhinal, parahippocampal, inferior parietal, insula, isthmus cingulate, lingual, supramarginal, and orbitofrontal regions.
Because the findings were observed in a population of cognitively normal and minimally impaired subjects, they suggest a role for sleep studies in assessing the risk for cognitive decline and Alzheimer’s disease, and in monitoring patients with the disease, reported Brendan P. Lucey, MD, and his colleagues. The report is in Science and Translational Medicine (Sci Transl Med. 2019 Jan 9;11:eaau6550).
“With the rising incidence of Alzheimer’s disease in an aging population, our findings have potential application in both clinical trials and patient screening for Alzheimer’s disease to noninvasively monitor for progression of Alzheimer’s disease pathology,” wrote Dr. Lucey, director of the Sleep Medicine Center and assistant professor of neurology at Washington University in St. Louis. “For instance, periodically measuring non-REM slow wave activity, in conjunction with other biomarkers, may have utility for monitoring Alzheimer’s disease risk or response to an Alzheimer’s disease treatment.”
Dr. Lucey and his colleagues examined sleep architecture and tau and amyloid deposition in 119 subjects enrolled in longitudinal aging studies. For 6 nights, subjects slept with a single-channel EEG monitor on. They also underwent cognitive testing and genotyping for Alzheimer’s disease risk factors.
Subjects were a mean of 74 years old. Almost 80% had normal cognition as measured by the Clinical Dementia Rating Scale (CDR); the remainder had very mild cognitive impairment (CDR 0.5)
Among those with positive biomarker findings, sleep architecture was altered in several ways: lower REM latency, lower wake after sleep onset, prolonged sleep-onset latency, and longer self-reported total sleep time. The differences were evident in those with normal cognition, but even more pronounced in those with mild cognitive impairment. Despite the longer sleep times, however, sleep efficiency was decreased.
Decreased non-REM slow wave activity was associated with increased tau deposition. The protein was largely concentrated in areas of typical Alzheimer’s disease pathology (entorhinal, parahippocampal, orbital frontal, precuneus, inferior parietal, and inferior temporal regions). There were no significant associations between non-REM slow wave activity and amyloid deposits.
Other sleep parameters, however, were associated with amyloid, including REM latency and sleep latency, “suggesting that as amyloid-beta deposition increased, the time to fall asleep and enter REM sleep decreased,” the investigators said.
Those with tau pathology also slept longer, reporting more daytime naps. “This suggests that participants with greater tau pathology experienced daytime sleepiness despite increased total sleep time.”
“These results, coupled with the non-REM slow wave activity findings, suggest that the quality of sleep decreases with increasing tau despite increased sleep time.” Questions about napping should probably be included in dementia screening discussions, they said.
The study was largely funded by the National Institutes of Health. Dr. Lucey had no financial conflicts.
SOURCE: Lucey BP et al. Sci Transl Med 2019 Jan 9;11:eaau6550.
The protein was evident in areas associated with memory consolidation, typically affected in Alzheimer’s disease: the entorhinal, parahippocampal, inferior parietal, insula, isthmus cingulate, lingual, supramarginal, and orbitofrontal regions.
Because the findings were observed in a population of cognitively normal and minimally impaired subjects, they suggest a role for sleep studies in assessing the risk for cognitive decline and Alzheimer’s disease, and in monitoring patients with the disease, reported Brendan P. Lucey, MD, and his colleagues. The report is in Science and Translational Medicine (Sci Transl Med. 2019 Jan 9;11:eaau6550).
“With the rising incidence of Alzheimer’s disease in an aging population, our findings have potential application in both clinical trials and patient screening for Alzheimer’s disease to noninvasively monitor for progression of Alzheimer’s disease pathology,” wrote Dr. Lucey, director of the Sleep Medicine Center and assistant professor of neurology at Washington University in St. Louis. “For instance, periodically measuring non-REM slow wave activity, in conjunction with other biomarkers, may have utility for monitoring Alzheimer’s disease risk or response to an Alzheimer’s disease treatment.”
Dr. Lucey and his colleagues examined sleep architecture and tau and amyloid deposition in 119 subjects enrolled in longitudinal aging studies. For 6 nights, subjects slept with a single-channel EEG monitor on. They also underwent cognitive testing and genotyping for Alzheimer’s disease risk factors.
Subjects were a mean of 74 years old. Almost 80% had normal cognition as measured by the Clinical Dementia Rating Scale (CDR); the remainder had very mild cognitive impairment (CDR 0.5)
Among those with positive biomarker findings, sleep architecture was altered in several ways: lower REM latency, lower wake after sleep onset, prolonged sleep-onset latency, and longer self-reported total sleep time. The differences were evident in those with normal cognition, but even more pronounced in those with mild cognitive impairment. Despite the longer sleep times, however, sleep efficiency was decreased.
Decreased non-REM slow wave activity was associated with increased tau deposition. The protein was largely concentrated in areas of typical Alzheimer’s disease pathology (entorhinal, parahippocampal, orbital frontal, precuneus, inferior parietal, and inferior temporal regions). There were no significant associations between non-REM slow wave activity and amyloid deposits.
Other sleep parameters, however, were associated with amyloid, including REM latency and sleep latency, “suggesting that as amyloid-beta deposition increased, the time to fall asleep and enter REM sleep decreased,” the investigators said.
Those with tau pathology also slept longer, reporting more daytime naps. “This suggests that participants with greater tau pathology experienced daytime sleepiness despite increased total sleep time.”
“These results, coupled with the non-REM slow wave activity findings, suggest that the quality of sleep decreases with increasing tau despite increased sleep time.” Questions about napping should probably be included in dementia screening discussions, they said.
The study was largely funded by the National Institutes of Health. Dr. Lucey had no financial conflicts.
SOURCE: Lucey BP et al. Sci Transl Med 2019 Jan 9;11:eaau6550.
The protein was evident in areas associated with memory consolidation, typically affected in Alzheimer’s disease: the entorhinal, parahippocampal, inferior parietal, insula, isthmus cingulate, lingual, supramarginal, and orbitofrontal regions.
Because the findings were observed in a population of cognitively normal and minimally impaired subjects, they suggest a role for sleep studies in assessing the risk for cognitive decline and Alzheimer’s disease, and in monitoring patients with the disease, reported Brendan P. Lucey, MD, and his colleagues. The report is in Science and Translational Medicine (Sci Transl Med. 2019 Jan 9;11:eaau6550).
“With the rising incidence of Alzheimer’s disease in an aging population, our findings have potential application in both clinical trials and patient screening for Alzheimer’s disease to noninvasively monitor for progression of Alzheimer’s disease pathology,” wrote Dr. Lucey, director of the Sleep Medicine Center and assistant professor of neurology at Washington University in St. Louis. “For instance, periodically measuring non-REM slow wave activity, in conjunction with other biomarkers, may have utility for monitoring Alzheimer’s disease risk or response to an Alzheimer’s disease treatment.”
Dr. Lucey and his colleagues examined sleep architecture and tau and amyloid deposition in 119 subjects enrolled in longitudinal aging studies. For 6 nights, subjects slept with a single-channel EEG monitor on. They also underwent cognitive testing and genotyping for Alzheimer’s disease risk factors.
Subjects were a mean of 74 years old. Almost 80% had normal cognition as measured by the Clinical Dementia Rating Scale (CDR); the remainder had very mild cognitive impairment (CDR 0.5)
Among those with positive biomarker findings, sleep architecture was altered in several ways: lower REM latency, lower wake after sleep onset, prolonged sleep-onset latency, and longer self-reported total sleep time. The differences were evident in those with normal cognition, but even more pronounced in those with mild cognitive impairment. Despite the longer sleep times, however, sleep efficiency was decreased.
Decreased non-REM slow wave activity was associated with increased tau deposition. The protein was largely concentrated in areas of typical Alzheimer’s disease pathology (entorhinal, parahippocampal, orbital frontal, precuneus, inferior parietal, and inferior temporal regions). There were no significant associations between non-REM slow wave activity and amyloid deposits.
Other sleep parameters, however, were associated with amyloid, including REM latency and sleep latency, “suggesting that as amyloid-beta deposition increased, the time to fall asleep and enter REM sleep decreased,” the investigators said.
Those with tau pathology also slept longer, reporting more daytime naps. “This suggests that participants with greater tau pathology experienced daytime sleepiness despite increased total sleep time.”
“These results, coupled with the non-REM slow wave activity findings, suggest that the quality of sleep decreases with increasing tau despite increased sleep time.” Questions about napping should probably be included in dementia screening discussions, they said.
The study was largely funded by the National Institutes of Health. Dr. Lucey had no financial conflicts.
SOURCE: Lucey BP et al. Sci Transl Med 2019 Jan 9;11:eaau6550.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: Cognitively normal subjects with tau deposition experience altered sleep patterns.
Major finding: Decreased time in non-REM deep sleep was associated with increased tau pathology in Alzheimer’s-affected brain regions and in cerebrospinal fluid.
Study details: The prospective longitudinal study comprised 119 subjects.
Disclosures: The authors reported no relevant financial disclosures.
Source: Lucey BP et al. Sci Transl Med. 2019 Jan 9;11:eaau6550.
Alcohol use, psychological distress associated with possible RBD
(RBD), according to a population-based cohort study published in Neurology. In addition, the results also replicate previous findings of an association between possible RBD and smoking, low education, and male sex.
The risk factors for RBD have been studied comparatively little. “While much is still unknown about RBD, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” according to Ronald B. Postuma, MD, an associate professor at McGill University, Montreal. “Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it.”
To assess sociodemographic, socioeconomic, and clinical correlates of possible RBD, Dr. Postuma and his colleagues examined baseline data collected between 2012 and 2015 in the Canadian Longitudinal Study on Aging (CLSA), which included 30,097 participants. To screen for possible RBD, the CLSA researchers asked patients, “Have you ever been told, or suspected yourself, that you seem to ‘act out your dreams’ while asleep [e.g., punching, flailing your arms in the air, making running movements, etc.]?” Participants answered additional questions to rule out RBD mimics. Patients with symptom onset before age 20 years, positive apnea screen, or a diagnosis of dementia, Alzheimer’s disease, parkinsonism, or Parkinson’s disease were excluded from analysis.
In all, 3,271 participants screened positive for possible RBD. After the investigators excluded participants with potential mimics, 958 patients (about 3.2% of the total population) remained in the analysis. Approximately 59% of patients with possible RBD were male, compared with 42% of controls. Patients with possible RBD were more likely to be married, in a common-law relationship, or widowed.
Participants with possible RBD had slightly less education (estimated mean, 13.2 years vs. 13.6 years) and lower income, compared with controls. Participants with possible RBD retired at a slightly younger age (57.5 years vs. 58.6 years) and were more likely to have retired because of health concerns (28.9% vs. 22.0%), compared with controls.
In addition, patients with possible RBD were more likely to drink more and to be moderate to heavy drinkers than controls; they were also more likely to be current or past smokers. Antidepressant use was more frequent and psychological distress was greater among participants with possible RBD.
When the investigators performed a multivariable logistic regression analysis, the associations between possible RBD and male sex and relationship status remained. Lower educational level, but not income level, also remained associated with possible RBD. Furthermore, retirement age and having reported retirement because of health concerns remained significantly associated with possible RBD, as did the amount of alcohol consumed weekly and moderate to heavy drinking. Sensitivity analyses did not change the results significantly.
One of the study’s limitations is its reliance on self-report to identify participants with possible RBD, the authors wrote. The prevalence of possible RBD in the study was 3.2%, but research using polysomnography has found a prevalence of about 1%. Thus, the majority of cases in this study may have other disorders such as restless legs syndrome or periodic limb movements. Furthermore, many participants who enact their dreams (such as unmarried people) are likely unaware of it. Finally, the researchers did not measure several variables of interest, such as consumption of caffeinated products.
“The main advantages of our current study are the large sample size; the systematic population-based sampling; the capacity to adjust for diverse potential confounding variables, including mental illness; and the ability to screen out RBD mimics,” the authors concluded.
SOURCE: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.
(RBD), according to a population-based cohort study published in Neurology. In addition, the results also replicate previous findings of an association between possible RBD and smoking, low education, and male sex.
The risk factors for RBD have been studied comparatively little. “While much is still unknown about RBD, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” according to Ronald B. Postuma, MD, an associate professor at McGill University, Montreal. “Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it.”
To assess sociodemographic, socioeconomic, and clinical correlates of possible RBD, Dr. Postuma and his colleagues examined baseline data collected between 2012 and 2015 in the Canadian Longitudinal Study on Aging (CLSA), which included 30,097 participants. To screen for possible RBD, the CLSA researchers asked patients, “Have you ever been told, or suspected yourself, that you seem to ‘act out your dreams’ while asleep [e.g., punching, flailing your arms in the air, making running movements, etc.]?” Participants answered additional questions to rule out RBD mimics. Patients with symptom onset before age 20 years, positive apnea screen, or a diagnosis of dementia, Alzheimer’s disease, parkinsonism, or Parkinson’s disease were excluded from analysis.
In all, 3,271 participants screened positive for possible RBD. After the investigators excluded participants with potential mimics, 958 patients (about 3.2% of the total population) remained in the analysis. Approximately 59% of patients with possible RBD were male, compared with 42% of controls. Patients with possible RBD were more likely to be married, in a common-law relationship, or widowed.
Participants with possible RBD had slightly less education (estimated mean, 13.2 years vs. 13.6 years) and lower income, compared with controls. Participants with possible RBD retired at a slightly younger age (57.5 years vs. 58.6 years) and were more likely to have retired because of health concerns (28.9% vs. 22.0%), compared with controls.
In addition, patients with possible RBD were more likely to drink more and to be moderate to heavy drinkers than controls; they were also more likely to be current or past smokers. Antidepressant use was more frequent and psychological distress was greater among participants with possible RBD.
When the investigators performed a multivariable logistic regression analysis, the associations between possible RBD and male sex and relationship status remained. Lower educational level, but not income level, also remained associated with possible RBD. Furthermore, retirement age and having reported retirement because of health concerns remained significantly associated with possible RBD, as did the amount of alcohol consumed weekly and moderate to heavy drinking. Sensitivity analyses did not change the results significantly.
One of the study’s limitations is its reliance on self-report to identify participants with possible RBD, the authors wrote. The prevalence of possible RBD in the study was 3.2%, but research using polysomnography has found a prevalence of about 1%. Thus, the majority of cases in this study may have other disorders such as restless legs syndrome or periodic limb movements. Furthermore, many participants who enact their dreams (such as unmarried people) are likely unaware of it. Finally, the researchers did not measure several variables of interest, such as consumption of caffeinated products.
“The main advantages of our current study are the large sample size; the systematic population-based sampling; the capacity to adjust for diverse potential confounding variables, including mental illness; and the ability to screen out RBD mimics,” the authors concluded.
SOURCE: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.
(RBD), according to a population-based cohort study published in Neurology. In addition, the results also replicate previous findings of an association between possible RBD and smoking, low education, and male sex.
The risk factors for RBD have been studied comparatively little. “While much is still unknown about RBD, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy,” according to Ronald B. Postuma, MD, an associate professor at McGill University, Montreal. “Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it.”
To assess sociodemographic, socioeconomic, and clinical correlates of possible RBD, Dr. Postuma and his colleagues examined baseline data collected between 2012 and 2015 in the Canadian Longitudinal Study on Aging (CLSA), which included 30,097 participants. To screen for possible RBD, the CLSA researchers asked patients, “Have you ever been told, or suspected yourself, that you seem to ‘act out your dreams’ while asleep [e.g., punching, flailing your arms in the air, making running movements, etc.]?” Participants answered additional questions to rule out RBD mimics. Patients with symptom onset before age 20 years, positive apnea screen, or a diagnosis of dementia, Alzheimer’s disease, parkinsonism, or Parkinson’s disease were excluded from analysis.
In all, 3,271 participants screened positive for possible RBD. After the investigators excluded participants with potential mimics, 958 patients (about 3.2% of the total population) remained in the analysis. Approximately 59% of patients with possible RBD were male, compared with 42% of controls. Patients with possible RBD were more likely to be married, in a common-law relationship, or widowed.
Participants with possible RBD had slightly less education (estimated mean, 13.2 years vs. 13.6 years) and lower income, compared with controls. Participants with possible RBD retired at a slightly younger age (57.5 years vs. 58.6 years) and were more likely to have retired because of health concerns (28.9% vs. 22.0%), compared with controls.
In addition, patients with possible RBD were more likely to drink more and to be moderate to heavy drinkers than controls; they were also more likely to be current or past smokers. Antidepressant use was more frequent and psychological distress was greater among participants with possible RBD.
When the investigators performed a multivariable logistic regression analysis, the associations between possible RBD and male sex and relationship status remained. Lower educational level, but not income level, also remained associated with possible RBD. Furthermore, retirement age and having reported retirement because of health concerns remained significantly associated with possible RBD, as did the amount of alcohol consumed weekly and moderate to heavy drinking. Sensitivity analyses did not change the results significantly.
One of the study’s limitations is its reliance on self-report to identify participants with possible RBD, the authors wrote. The prevalence of possible RBD in the study was 3.2%, but research using polysomnography has found a prevalence of about 1%. Thus, the majority of cases in this study may have other disorders such as restless legs syndrome or periodic limb movements. Furthermore, many participants who enact their dreams (such as unmarried people) are likely unaware of it. Finally, the researchers did not measure several variables of interest, such as consumption of caffeinated products.
“The main advantages of our current study are the large sample size; the systematic population-based sampling; the capacity to adjust for diverse potential confounding variables, including mental illness; and the ability to screen out RBD mimics,” the authors concluded.
SOURCE: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.
FROM NEUROLOGY
Key clinical point: Alcohol use and psychological distress are associated with possible REM sleep behavior disorder.
Major finding: A self-report questionnaire yielded a 3.2% prevalence of possible REM sleep behavior disorder.
Study details: A prospective, population-based cohort study of 30,097 participants.
Disclosures: The Canadian government provided funding for the research.
Source: Postuma RB et al. Neurology. 2018 Dec 26. doi: 10.1212/WNL.0000000000006849.
Daclizumab beta may be superior to interferon beta on MS disability progression
(MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.
Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.
The phase 3 DECIDE study (NCT01064401) compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).
To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics, Stanley L. Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.
Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.
Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups were well balanced in terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.
Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.
The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.
In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.
“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.
Biogen and AbbVie Biotherapeutics supported the study.
SOURCE: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.
This article was updated on 3/22/19.
(MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.
Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.
The phase 3 DECIDE study (NCT01064401) compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).
To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics, Stanley L. Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.
Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.
Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups were well balanced in terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.
Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.
The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.
In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.
“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.
Biogen and AbbVie Biotherapeutics supported the study.
SOURCE: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.
This article was updated on 3/22/19.
(MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.
Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.
The phase 3 DECIDE study (NCT01064401) compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).
To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics, Stanley L. Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.
Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.
Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups were well balanced in terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.
Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.
The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.
In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.
“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.
Biogen and AbbVie Biotherapeutics supported the study.
SOURCE: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.
This article was updated on 3/22/19.
FROM MULTIPLE SCLEROSIS JOURNAL
Key clinical point: Daclizumab beta reduces the risk of 24-week sustained worsening on the MSFC by 20%, compared with interferon beta-1a.
Major finding: Daclizumab appears superior to interferon beta-1a regardless of patients’ demographic or disease characteristics.
Study details: A post hoc analysis of the DECIDE study, which included 1,841 patients with relapsing-remitting MS.
Disclosures: Biogen and AbbVie Biotherapeutics supported the DECIDE study.
Source: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.
AAN publishes position statement on brain death
In a position statement published online ahead of print Jan. 2 in Neurology, Such uniformity would reduce uncertainty and improve patient care, according to the authors. The statement, which was drafted by the AAN’s Brain Death Working Group, also supports the development of uniform policies regarding brain death and its determination within American medical institutions. Finally, the document provides neurologists with guidance for responding to requests for accommodation, including objections to the determination of brain death and to the withdrawal of organ-sustaining technology.
The AAN defines brain death as death resulting from irreversible loss of function of the entire brain. The Uniform Determination of Death Act of 1981 held that brain death and circulatory death (that is, death resulting from irreversible loss of function of the circulatory system) are equivalent, and the AAN acknowledges this equivalence.
The two current medical standards for brain death are the AAN’s 2010 Evidence-Based Guideline Update: Determining Brain Death in Adults and the 2011 Guidelines for the Determination of Brain Death in Infants and Children, which was published by the pediatric section of the Society of Critical Care Medicine, the sections of neurology and critical care of the American Academy of Pediatrics, and the Child Neurology Society. “The AAN is unaware of any cases in which compliant application of the brain death guidelines led to inaccurate determination of death with return of any brain function, including consciousness, brainstem reflexes, or ventilatory effort,” according to their 2019 statement.
The only jurisdiction with laws that specifically defer to these standards, however, is Nevada. The vagueness of most states’ laws has contributed to divergent legal interpretations and idiosyncratic standards for determining brain death, according to the statement.
“The AAN believes that a specific, uniform standard for the determination of brain death is critically important to provide the highest quality patient-centered neurologic and end-of-life care,” said James Russell, DO, MS, a neurologist at Lahey Hospital and Medical Center in Burlington, Mass., and lead author of the position statement. “The AAN supports the development of legislation in every state modeled after the Nevada statute, which specifically defers to these current adult and pediatric brain death guidelines and any future updates.”
In addition to uniform institutional policies for determining brain death within U.S. medical facilities, the AAN calls for the development of training programs and credentialing mechanisms for physicians who determine brain death, regardless of their specialties. The association also supports research that enhances understanding of brain death and enhanced professional and public education.
While expressing respect and sympathy for requests for limited accommodation, the AAN asserts that these requests “must be based on the values of the patient, and not those of loved ones or other surrogate decision makers.” The association further observes that physicians have no ethical obligation to provide medical treatment to a deceased patient. New Jersey is the only state that legally obliges physicians to provide indefinite accommodation and continued application of organ-sustaining technology.
“The AAN believes that its members have both the moral authority and professional responsibility, when lawful, to perform a brain death evaluation, including apnea testing, after informing a patient’s loved ones or lawful surrogates of that intention, but without obligation to obtain informed consent,” according to the statement. “This position is analogous to the authority and responsibility historically granted to the medical profession to determine circulatory death without the requirement for additional informed consent.”
If a dispute about indefinite accommodation cannot be resolved, it is acceptable for a physician to withdraw organ-sustaining technology unilaterally over the objection of loved ones when legally permitted, according to the AAN. Such unilateral action is a measure of last resort and does not apply when the patient is a pregnant woman, said the authors. In the latter case, the ethical analysis should focus mainly on the welfare of the fetus.
The AAN provided financial support for the Brain Death Working Group’s efforts. The statement’s authors reported no relevant disclosures. The American Neurological Association and the Child Neurology Society have endorsed the AAN’s position statement.
SOURCE: Russell JA et al. Neurology. 2018 Jan 2. doi: 10.1212/WNL.0000000000006750.
In a position statement published online ahead of print Jan. 2 in Neurology, Such uniformity would reduce uncertainty and improve patient care, according to the authors. The statement, which was drafted by the AAN’s Brain Death Working Group, also supports the development of uniform policies regarding brain death and its determination within American medical institutions. Finally, the document provides neurologists with guidance for responding to requests for accommodation, including objections to the determination of brain death and to the withdrawal of organ-sustaining technology.
The AAN defines brain death as death resulting from irreversible loss of function of the entire brain. The Uniform Determination of Death Act of 1981 held that brain death and circulatory death (that is, death resulting from irreversible loss of function of the circulatory system) are equivalent, and the AAN acknowledges this equivalence.
The two current medical standards for brain death are the AAN’s 2010 Evidence-Based Guideline Update: Determining Brain Death in Adults and the 2011 Guidelines for the Determination of Brain Death in Infants and Children, which was published by the pediatric section of the Society of Critical Care Medicine, the sections of neurology and critical care of the American Academy of Pediatrics, and the Child Neurology Society. “The AAN is unaware of any cases in which compliant application of the brain death guidelines led to inaccurate determination of death with return of any brain function, including consciousness, brainstem reflexes, or ventilatory effort,” according to their 2019 statement.
The only jurisdiction with laws that specifically defer to these standards, however, is Nevada. The vagueness of most states’ laws has contributed to divergent legal interpretations and idiosyncratic standards for determining brain death, according to the statement.
“The AAN believes that a specific, uniform standard for the determination of brain death is critically important to provide the highest quality patient-centered neurologic and end-of-life care,” said James Russell, DO, MS, a neurologist at Lahey Hospital and Medical Center in Burlington, Mass., and lead author of the position statement. “The AAN supports the development of legislation in every state modeled after the Nevada statute, which specifically defers to these current adult and pediatric brain death guidelines and any future updates.”
In addition to uniform institutional policies for determining brain death within U.S. medical facilities, the AAN calls for the development of training programs and credentialing mechanisms for physicians who determine brain death, regardless of their specialties. The association also supports research that enhances understanding of brain death and enhanced professional and public education.
While expressing respect and sympathy for requests for limited accommodation, the AAN asserts that these requests “must be based on the values of the patient, and not those of loved ones or other surrogate decision makers.” The association further observes that physicians have no ethical obligation to provide medical treatment to a deceased patient. New Jersey is the only state that legally obliges physicians to provide indefinite accommodation and continued application of organ-sustaining technology.
“The AAN believes that its members have both the moral authority and professional responsibility, when lawful, to perform a brain death evaluation, including apnea testing, after informing a patient’s loved ones or lawful surrogates of that intention, but without obligation to obtain informed consent,” according to the statement. “This position is analogous to the authority and responsibility historically granted to the medical profession to determine circulatory death without the requirement for additional informed consent.”
If a dispute about indefinite accommodation cannot be resolved, it is acceptable for a physician to withdraw organ-sustaining technology unilaterally over the objection of loved ones when legally permitted, according to the AAN. Such unilateral action is a measure of last resort and does not apply when the patient is a pregnant woman, said the authors. In the latter case, the ethical analysis should focus mainly on the welfare of the fetus.
The AAN provided financial support for the Brain Death Working Group’s efforts. The statement’s authors reported no relevant disclosures. The American Neurological Association and the Child Neurology Society have endorsed the AAN’s position statement.
SOURCE: Russell JA et al. Neurology. 2018 Jan 2. doi: 10.1212/WNL.0000000000006750.
In a position statement published online ahead of print Jan. 2 in Neurology, Such uniformity would reduce uncertainty and improve patient care, according to the authors. The statement, which was drafted by the AAN’s Brain Death Working Group, also supports the development of uniform policies regarding brain death and its determination within American medical institutions. Finally, the document provides neurologists with guidance for responding to requests for accommodation, including objections to the determination of brain death and to the withdrawal of organ-sustaining technology.
The AAN defines brain death as death resulting from irreversible loss of function of the entire brain. The Uniform Determination of Death Act of 1981 held that brain death and circulatory death (that is, death resulting from irreversible loss of function of the circulatory system) are equivalent, and the AAN acknowledges this equivalence.
The two current medical standards for brain death are the AAN’s 2010 Evidence-Based Guideline Update: Determining Brain Death in Adults and the 2011 Guidelines for the Determination of Brain Death in Infants and Children, which was published by the pediatric section of the Society of Critical Care Medicine, the sections of neurology and critical care of the American Academy of Pediatrics, and the Child Neurology Society. “The AAN is unaware of any cases in which compliant application of the brain death guidelines led to inaccurate determination of death with return of any brain function, including consciousness, brainstem reflexes, or ventilatory effort,” according to their 2019 statement.
The only jurisdiction with laws that specifically defer to these standards, however, is Nevada. The vagueness of most states’ laws has contributed to divergent legal interpretations and idiosyncratic standards for determining brain death, according to the statement.
“The AAN believes that a specific, uniform standard for the determination of brain death is critically important to provide the highest quality patient-centered neurologic and end-of-life care,” said James Russell, DO, MS, a neurologist at Lahey Hospital and Medical Center in Burlington, Mass., and lead author of the position statement. “The AAN supports the development of legislation in every state modeled after the Nevada statute, which specifically defers to these current adult and pediatric brain death guidelines and any future updates.”
In addition to uniform institutional policies for determining brain death within U.S. medical facilities, the AAN calls for the development of training programs and credentialing mechanisms for physicians who determine brain death, regardless of their specialties. The association also supports research that enhances understanding of brain death and enhanced professional and public education.
While expressing respect and sympathy for requests for limited accommodation, the AAN asserts that these requests “must be based on the values of the patient, and not those of loved ones or other surrogate decision makers.” The association further observes that physicians have no ethical obligation to provide medical treatment to a deceased patient. New Jersey is the only state that legally obliges physicians to provide indefinite accommodation and continued application of organ-sustaining technology.
“The AAN believes that its members have both the moral authority and professional responsibility, when lawful, to perform a brain death evaluation, including apnea testing, after informing a patient’s loved ones or lawful surrogates of that intention, but without obligation to obtain informed consent,” according to the statement. “This position is analogous to the authority and responsibility historically granted to the medical profession to determine circulatory death without the requirement for additional informed consent.”
If a dispute about indefinite accommodation cannot be resolved, it is acceptable for a physician to withdraw organ-sustaining technology unilaterally over the objection of loved ones when legally permitted, according to the AAN. Such unilateral action is a measure of last resort and does not apply when the patient is a pregnant woman, said the authors. In the latter case, the ethical analysis should focus mainly on the welfare of the fetus.
The AAN provided financial support for the Brain Death Working Group’s efforts. The statement’s authors reported no relevant disclosures. The American Neurological Association and the Child Neurology Society have endorsed the AAN’s position statement.
SOURCE: Russell JA et al. Neurology. 2018 Jan 2. doi: 10.1212/WNL.0000000000006750.
FROM NEUROLOGY
Key clinical point: The AAN calls for uniform brain death laws, policies, and practices.
Major finding: The association published a position statement online on January 2.
Study details: The AAN’s Brain Death Working Group drafted the statement.
Disclosures: The authors reported no relevant disclosures, and the American Academy of Neurology funded their work.
Source: Russell JA et al. Neurology. 2018 Jan 2. doi: 10.1212/WNL.0000000000006750.
Managing menopausal vasomotor and genitourinary symptoms after breast cancer
Breast cancer survivors entering menopause face the risk of several menopausal symptoms:
- Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.1 That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).
Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.
- Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
- Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.
Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.
In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).
CASE 1
Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.
Strategy #1: Lifestyle adaptations
First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:
- increase physical activity
- reduce body weight by approximately 10% (if overweight or obese)
- reduce alcohol consumption
- stop smoking
- ensure adequate intake of calcium (1,200 mg, preferably by diet)
- optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.
The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.
Continue to: Strategy #2: OTC compounds...
Strategy #2: OTC compounds
Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,2 or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.
Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.
CASE 1 Continued
Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.
Strategy #3: Prescription medication
When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.
When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.3 Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.
For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.
Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.
Continue to: Not a recommended strategy: Systemic hormone therapy
Not a recommended strategy: Systemic hormone therapy
Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.4 At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.
CASE 2
Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.
The challenge of managing GSM
What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?
Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.5 The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.
For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.
The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.6 Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.1,3
Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.
Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.7 In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.
Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.
Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years8); again, however, it has not been tested in patients with breast cancer.
Continue to: Nonhormone therapies...
Nonhormone therapies
Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.9
Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.5
Newly arrived and on the horizon
Where does this review of available treatments leave us? Regrettably, with many women who experience painful intercourse and vaginal dryness despite what is available for treating their problems, and who continue looking to medical science and women’s health care for new options. So, what is coming next for these suffering patients? Here is a quick and selective run-through:
KNDy neurons. For hot flashes, there is the promise of nonhormonal treatment using these neurons, believed to be involved in reproduction by triggering expression of various compounds— particularly neurokinin B, which mediates hot flashes.1
Estetrol. In testing for use in treating hot flashes and its effect on GSM is this pregnancy-associated natural hormone that, importantly, did not stimulate breast cancer in a rat model.2 More evidence of efficacy is needed.
Lasers. For vaginal atrophy, many women are choosing treatment with the laser. Keep in mind, however, that, although lasers are FDA-approved devices, they do not have the FDA’s endorsement for use in vaginal atrophy, and have not been well-tested for their effectiveness for this indication in women with breast cancer who have taken an aromatase inhibitor. ACOG, NAMS, and the Endocrine Society have urged that additional trials be conducted, and have stated that the laser for vaginal atrophy cannot be recommended until there are more data on safety and efficacy.2
Lower-dose soft-gel vaginal estrogen suppositories have recently been approved by the FDA at 4 and 10 µg.3 The formulations are only minimally absorbed, potentially making them a good option for women who have had breast cancer.
Lasofoxifene, a selective estrogen-receptor modulator not yet approved by the FDA, has been shown to ameliorate vaginal changes.4 The drug is neutral or protective on the breast, but is now being tested in women with resistant breast cancer and unlikely to become available for GSM.
References
1. Anderson RA, Skorupskaite K, Sassarini J. The neurokinin B pathway in the treatment of menopausal hot flushes. Climacteric. 2018;1-4.
2. Gérard C, Mestdagt M, Tskitishvili E, et al. Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms. Oncotarget. 2015;6(19):17621–17636.
3. Simon JA, Archer DF, Constantine GD, et al. A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: efficacy and pharmacokinetic data review. Maturitas. 2017;99:51-58.
4. Bachmann G, Gass M, Kagan R, et al. Lasofoxifene (LASO), a next generation selective estrogen response modulator (SERM), improves dyspareunia in postmenopausal women with vaginal atrophy (VA). Menopause. 2005;12:238.
Treatment begins with a conversation
Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”
First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.
1. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24:728-753.
2. McGarry K, Geary M, Gopinath V. Beyond estrogen: treatment options for hot flashes. Clin Ther. 2018;40(10):1778-1786.
3. Santen RJ, Stuenkel CA, Davis SR, et al. Managing menopausal symptoms and associated clinical issues in breast cancer survivors. J Clin Endocrinol Metab. 2017;102:3647-3661.
4. Faubion SS, Loprinzi CL, Ruddy KJ. Management of hormone deprivation symptoms after cancer. Mayo Clin Proc. 2016;91:1133-1146.
5. Faubion SS, Larkin LC, Stuenkel, et al. 2018;25(6):596-608.
6. American College of Obstertricians and Gynecologists’ Committee on Gynecologic Practice, Farrell R. ACOG Committee Opinion No. 659: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Obstet Gynecol. 2016;127:e93-e96.
7. Simon JA, Altomare C, Cort S, Jiang W. Overall safety of ospemifene in postmenopausal women from placebocontrolled Phase 2 and 3 trials. J Womens Health (Larchmt). 2018;27(1):14-23.
8. Pinkerton JV, Thomas S. Use of SERMs for treatment in postmenopausal women. Steroid Biochem Mol Biol. 2014;142:142-54.
9. Goetsch MF, Lim JY, Caughey AB. A practical solution for dyspareunia in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2015;33:3394-3400.
JoAnn V. Pinkerton, MD
Dr. Pinkerton is Professor, Department of Obstetrics and Gynecology, and Director, Midlife Health, University of Virginia Health System, Charlottesville, Virginia. She is also Executive Director of the North American Menopause Society. She serves on the OBG Management Board of Editors.
The author reports no financial relationships related to this article.
JoAnn V. Pinkerton, MD
Dr. Pinkerton is Professor, Department of Obstetrics and Gynecology, and Director, Midlife Health, University of Virginia Health System, Charlottesville, Virginia. She is also Executive Director of the North American Menopause Society. She serves on the OBG Management Board of Editors.
The author reports no financial relationships related to this article.
JoAnn V. Pinkerton, MD
Dr. Pinkerton is Professor, Department of Obstetrics and Gynecology, and Director, Midlife Health, University of Virginia Health System, Charlottesville, Virginia. She is also Executive Director of the North American Menopause Society. She serves on the OBG Management Board of Editors.
The author reports no financial relationships related to this article.
Breast cancer survivors entering menopause face the risk of several menopausal symptoms:
- Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.1 That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).
Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.
- Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
- Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.
Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.
In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).
CASE 1
Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.
Strategy #1: Lifestyle adaptations
First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:
- increase physical activity
- reduce body weight by approximately 10% (if overweight or obese)
- reduce alcohol consumption
- stop smoking
- ensure adequate intake of calcium (1,200 mg, preferably by diet)
- optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.
The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.
Continue to: Strategy #2: OTC compounds...
Strategy #2: OTC compounds
Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,2 or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.
Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.
CASE 1 Continued
Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.
Strategy #3: Prescription medication
When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.
When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.3 Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.
For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.
Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.
Continue to: Not a recommended strategy: Systemic hormone therapy
Not a recommended strategy: Systemic hormone therapy
Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.4 At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.
CASE 2
Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.
The challenge of managing GSM
What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?
Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.5 The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.
For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.
The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.6 Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.1,3
Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.
Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.7 In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.
Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.
Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years8); again, however, it has not been tested in patients with breast cancer.
Continue to: Nonhormone therapies...
Nonhormone therapies
Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.9
Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.5
Newly arrived and on the horizon
Where does this review of available treatments leave us? Regrettably, with many women who experience painful intercourse and vaginal dryness despite what is available for treating their problems, and who continue looking to medical science and women’s health care for new options. So, what is coming next for these suffering patients? Here is a quick and selective run-through:
KNDy neurons. For hot flashes, there is the promise of nonhormonal treatment using these neurons, believed to be involved in reproduction by triggering expression of various compounds— particularly neurokinin B, which mediates hot flashes.1
Estetrol. In testing for use in treating hot flashes and its effect on GSM is this pregnancy-associated natural hormone that, importantly, did not stimulate breast cancer in a rat model.2 More evidence of efficacy is needed.
Lasers. For vaginal atrophy, many women are choosing treatment with the laser. Keep in mind, however, that, although lasers are FDA-approved devices, they do not have the FDA’s endorsement for use in vaginal atrophy, and have not been well-tested for their effectiveness for this indication in women with breast cancer who have taken an aromatase inhibitor. ACOG, NAMS, and the Endocrine Society have urged that additional trials be conducted, and have stated that the laser for vaginal atrophy cannot be recommended until there are more data on safety and efficacy.2
Lower-dose soft-gel vaginal estrogen suppositories have recently been approved by the FDA at 4 and 10 µg.3 The formulations are only minimally absorbed, potentially making them a good option for women who have had breast cancer.
Lasofoxifene, a selective estrogen-receptor modulator not yet approved by the FDA, has been shown to ameliorate vaginal changes.4 The drug is neutral or protective on the breast, but is now being tested in women with resistant breast cancer and unlikely to become available for GSM.
References
1. Anderson RA, Skorupskaite K, Sassarini J. The neurokinin B pathway in the treatment of menopausal hot flushes. Climacteric. 2018;1-4.
2. Gérard C, Mestdagt M, Tskitishvili E, et al. Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms. Oncotarget. 2015;6(19):17621–17636.
3. Simon JA, Archer DF, Constantine GD, et al. A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: efficacy and pharmacokinetic data review. Maturitas. 2017;99:51-58.
4. Bachmann G, Gass M, Kagan R, et al. Lasofoxifene (LASO), a next generation selective estrogen response modulator (SERM), improves dyspareunia in postmenopausal women with vaginal atrophy (VA). Menopause. 2005;12:238.
Treatment begins with a conversation
Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”
First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.
Breast cancer survivors entering menopause face the risk of several menopausal symptoms:
- Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.1 That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).
Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.
- Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
- Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.
Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.
In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).
CASE 1
Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.
Strategy #1: Lifestyle adaptations
First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:
- increase physical activity
- reduce body weight by approximately 10% (if overweight or obese)
- reduce alcohol consumption
- stop smoking
- ensure adequate intake of calcium (1,200 mg, preferably by diet)
- optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.
The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.
Continue to: Strategy #2: OTC compounds...
Strategy #2: OTC compounds
Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,2 or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.
Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.
CASE 1 Continued
Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.
Strategy #3: Prescription medication
When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.
When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.3 Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.
For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.
Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.
Continue to: Not a recommended strategy: Systemic hormone therapy
Not a recommended strategy: Systemic hormone therapy
Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.4 At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.
CASE 2
Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.
The challenge of managing GSM
What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?
Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.5 The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.
For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.
The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.6 Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.1,3
Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.
Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.7 In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.
Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.
Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years8); again, however, it has not been tested in patients with breast cancer.
Continue to: Nonhormone therapies...
Nonhormone therapies
Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.9
Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.5
Newly arrived and on the horizon
Where does this review of available treatments leave us? Regrettably, with many women who experience painful intercourse and vaginal dryness despite what is available for treating their problems, and who continue looking to medical science and women’s health care for new options. So, what is coming next for these suffering patients? Here is a quick and selective run-through:
KNDy neurons. For hot flashes, there is the promise of nonhormonal treatment using these neurons, believed to be involved in reproduction by triggering expression of various compounds— particularly neurokinin B, which mediates hot flashes.1
Estetrol. In testing for use in treating hot flashes and its effect on GSM is this pregnancy-associated natural hormone that, importantly, did not stimulate breast cancer in a rat model.2 More evidence of efficacy is needed.
Lasers. For vaginal atrophy, many women are choosing treatment with the laser. Keep in mind, however, that, although lasers are FDA-approved devices, they do not have the FDA’s endorsement for use in vaginal atrophy, and have not been well-tested for their effectiveness for this indication in women with breast cancer who have taken an aromatase inhibitor. ACOG, NAMS, and the Endocrine Society have urged that additional trials be conducted, and have stated that the laser for vaginal atrophy cannot be recommended until there are more data on safety and efficacy.2
Lower-dose soft-gel vaginal estrogen suppositories have recently been approved by the FDA at 4 and 10 µg.3 The formulations are only minimally absorbed, potentially making them a good option for women who have had breast cancer.
Lasofoxifene, a selective estrogen-receptor modulator not yet approved by the FDA, has been shown to ameliorate vaginal changes.4 The drug is neutral or protective on the breast, but is now being tested in women with resistant breast cancer and unlikely to become available for GSM.
References
1. Anderson RA, Skorupskaite K, Sassarini J. The neurokinin B pathway in the treatment of menopausal hot flushes. Climacteric. 2018;1-4.
2. Gérard C, Mestdagt M, Tskitishvili E, et al. Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms. Oncotarget. 2015;6(19):17621–17636.
3. Simon JA, Archer DF, Constantine GD, et al. A vaginal estradiol softgel capsule, TX-004HR, has negligible to very low systemic absorption of estradiol: efficacy and pharmacokinetic data review. Maturitas. 2017;99:51-58.
4. Bachmann G, Gass M, Kagan R, et al. Lasofoxifene (LASO), a next generation selective estrogen response modulator (SERM), improves dyspareunia in postmenopausal women with vaginal atrophy (VA). Menopause. 2005;12:238.
Treatment begins with a conversation
Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”
First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.
1. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24:728-753.
2. McGarry K, Geary M, Gopinath V. Beyond estrogen: treatment options for hot flashes. Clin Ther. 2018;40(10):1778-1786.
3. Santen RJ, Stuenkel CA, Davis SR, et al. Managing menopausal symptoms and associated clinical issues in breast cancer survivors. J Clin Endocrinol Metab. 2017;102:3647-3661.
4. Faubion SS, Loprinzi CL, Ruddy KJ. Management of hormone deprivation symptoms after cancer. Mayo Clin Proc. 2016;91:1133-1146.
5. Faubion SS, Larkin LC, Stuenkel, et al. 2018;25(6):596-608.
6. American College of Obstertricians and Gynecologists’ Committee on Gynecologic Practice, Farrell R. ACOG Committee Opinion No. 659: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Obstet Gynecol. 2016;127:e93-e96.
7. Simon JA, Altomare C, Cort S, Jiang W. Overall safety of ospemifene in postmenopausal women from placebocontrolled Phase 2 and 3 trials. J Womens Health (Larchmt). 2018;27(1):14-23.
8. Pinkerton JV, Thomas S. Use of SERMs for treatment in postmenopausal women. Steroid Biochem Mol Biol. 2014;142:142-54.
9. Goetsch MF, Lim JY, Caughey AB. A practical solution for dyspareunia in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2015;33:3394-3400.
1. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24:728-753.
2. McGarry K, Geary M, Gopinath V. Beyond estrogen: treatment options for hot flashes. Clin Ther. 2018;40(10):1778-1786.
3. Santen RJ, Stuenkel CA, Davis SR, et al. Managing menopausal symptoms and associated clinical issues in breast cancer survivors. J Clin Endocrinol Metab. 2017;102:3647-3661.
4. Faubion SS, Loprinzi CL, Ruddy KJ. Management of hormone deprivation symptoms after cancer. Mayo Clin Proc. 2016;91:1133-1146.
5. Faubion SS, Larkin LC, Stuenkel, et al. 2018;25(6):596-608.
6. American College of Obstertricians and Gynecologists’ Committee on Gynecologic Practice, Farrell R. ACOG Committee Opinion No. 659: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Obstet Gynecol. 2016;127:e93-e96.
7. Simon JA, Altomare C, Cort S, Jiang W. Overall safety of ospemifene in postmenopausal women from placebocontrolled Phase 2 and 3 trials. J Womens Health (Larchmt). 2018;27(1):14-23.
8. Pinkerton JV, Thomas S. Use of SERMs for treatment in postmenopausal women. Steroid Biochem Mol Biol. 2014;142:142-54.
9. Goetsch MF, Lim JY, Caughey AB. A practical solution for dyspareunia in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2015;33:3394-3400.
Actionable mutations more likely in women with both breast and uterine cancer
Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.
The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.
“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.
The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.
That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.
A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–3), and 6.8% of women with no personal cancer history (P less than .001).
Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.
When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).
While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.
“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.
Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.
The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.
“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.
The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.
That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.
A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–3), and 6.8% of women with no personal cancer history (P less than .001).
Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.
When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).
While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.
“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.
Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
Women with both breast and uterine cancer are more likely to carry genetic mutations than women with either breast or uterine cancer alone, according to results of a retrospective analysis of test results.
The majority of the mutations identified were actionable, suggesting that women with breast and uterine cancer should be offered expanded genetic testing, authors of the analysis wrote in Gynecologic Oncology.
“Expanded testing for patients with breast and uterine cancer can help guide management by identifying more patients who may benefit from additional surveillance, along with at-risk family members,” said Kelly Fulk, an oncology genetic specialist at Ambry Genetics, and her coauthors.
The analysis by Ms. Fulk and her colleagues at St. Thomas Health, Nashville, and the University of California, Irvine, was based on a cohort of 52,000 women who had undergone multigene panel testing.
That cohort included 1,650 women with both breast and uterine cancer, of whom about 70% were white, and more than 94% were older than age 50 years at the time of testing. Their median age at first diagnosis was 56 years for breast cancer and 58 years for uterine cancer.
A total of 231 women with breast and uterine cancer, or 14.0%, carried at least one pathogenic mutation or likely pathogenic variant, Ms. Fulk and her colleagues reported. By comparison, mutations were seen in 9.3% of women with breast cancer only (P less than .001), 11.5% of women with uterine cancer only (P = 4.63 x 10–3), and 6.8% of women with no personal cancer history (P less than .001).
Women with both breast and uterine cancer more often had mutations in ATM, BARD1, BRCA2, MSH2, MSH6, PALB2, PMS2, and PTEN, when compared with those women with no personal cancer history, according to the report by Ms. Fulk and her coauthors.
When compared with women with just breast cancer, the women with both breast and uterine cancer more often had mutations in BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN, they added, noting that women with both cancers were twice as likely to have a BRCA1 mutation (odds ratio, 2.01; 95% confidence interval, 1.08-3.39, P = .016).
While this study had limitations, including its retrospective nature and use of genetic tests with varying numbers of genes analyzed, authors said the results nonetheless support expanded testing in women with both breast and uterine cancers to help guide therapy and cancer surveillance.
“Mutations associated with hereditary breast and ovarian cancer, Lynch syndrome, Cowden syndrome, and Li-Fraumeni syndrome have clear guidelines regarding management and surveillance for other cancers, which can benefit patients and their at-risk family members,” the investigators said.
Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics. No other disclosures were provided.
SOURCE: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.
FROM GYNECOLOGIC ONCOLOGY
Key clinical point: Women with both breast and uterine cancer are more likely to carry actionable mutations than do women with breast or uterine cancer alone.
Major finding: At least one actionable mutation was seen in 14% of women with breast and uterine cancer, compared with 9.3% of women with breast cancer only, 11.5% of women with uterine cancer only, and 6.8% of women with no personal cancer history.
Study details: A retrospective analysis of a cohort of nearly 52,000 patients who underwent multigene panel testing.
Disclosures: Ms. Fulk and five coauthors reported that they are paid employees of Ambry Genetics.
Source: Fulk K et al. Gynecol Oncol. 2019 Jan 3. doi: 10.1016/j.ygyno.2018.12.021.