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Patients with migraine experienced about a 60% reduction in pain intensity and number of headache days per month after exposure to green light therapy, according to results of a small study from the University of Arizona, Tucson.

“This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, “ senior author Mohab M. Ibrahim, MD, PhD, said in a press release. “Now I have another tool in my toolbox to treat one of the most difficult neurologic conditions – migraine.”

“Given the safety, affordability, and efficacy of green light exposure, there is merit to conduct a larger study,” he and coauthors from the university wrote in their paper.

The study included 29 adult patients (average age 52.2 years), 22 with chronic migraine and the rest with episodic migraine who were recruited from the University of Arizona/Banner Medical Center chronic pain clinic. To be included, patients had to meet the International Headache Society diagnostic criteria for chronic or episodic migraine, have an average headache pain intensity of 5 out of 10 or greater on the numeric pain scale (NPS) over the 10 weeks prior to enrolling in the study, and be dissatisfied with their current migraine therapy.

The patients were free to start, continue, or discontinue any other migraine treatments as recommended by their physicians as long as this was reported to the study team.
 

White versus green

The one-way crossover design involved exposure to 10 weeks of white light emitting diodes, for 1-2 hours per day, followed by a 2-week washout period and then 10 weeks’ exposure to green light emitting diodes (GLED) for the same daily duration. The protocol involved use of a light strip emitting an intensity of between 4 and 100 lux measured at approximately 2 m and 1 m from a lux meter.

Patients were instructed to use the light in a dark room, without falling asleep, and to participate in activities that did not require external light sources, such as listening to music, reading books, doing exercises, or engaging in similar activities. The daily minimum exposure of 1 hour, up to a maximum of 2 hours, was to be completed in one sitting.

The primary outcome measure was the number of headache days per month, defined as days with moderate to severe headache pain for at least 4 hours. Secondary outcomes included perceived reduction in duration and intensity of the headache phase of the migraine episodes assessed every 2 weeks with the NPS, improved ability to fall and stay asleep, improved ability to perform work and daily activity, improved quality of life, and reduction of pain medications.

The researchers found that when the patients with chronic migraine and episodic migraine were examined as separate groups, white light exposure did not significantly reduce the number of headache days per month, but when the chronic migraine and episodic migraine groups were combined there was a significant reduction from 18.2 to 16.5 headache days per month.

On the other hand, green light did result in significantly reduced headache days both in the separate (from 7.9 to 2.4 days in the episodic migraine group and 22.3 to 9.4 days in the chronic migraine group) and combined groups (from 18.4 to 7.4 days).

“While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes,” the authors reported.

“The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them,” coauthor Amol M. Patwardhan, MD, PhD, said in the press release. “The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures,” said Dr. Patwardhan, associate professor and vice chair of research in the University of Arizona’s department of anesthesiology.
 

Better than white light

Asked to comment on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said research has shown for some time that exposure to green light has beneficial effects in migraine patients. This study, although small, does indicate that green light is more beneficial than is white light and reduces headache days and intensity. “I believe patients would be willing to spend 1-2 hours a day in green light to reduce and improve their migraine with few side effects. A larger randomized trial should be done,” he said.

The study was funded by support from the National Center for Complementary and Integrative Health (to Dr. Ibrahim), the Comprehensive Chronic Pain and Addiction Center–University of Arizona, and the University of Arizona CHiLLI initiative. Dr. Ibrahim and one coauthor have a patent pending through the University of Arizona for use of green light therapy for the management of chronic pain. Dr. Rapoport is a former president of the International Headache Society. He is an editor of Headache and CNS Drugs, and Editor-in-Chief of Neurology Reviews. He reviews for many peer-reviewed journals such as Cephalalgia, Neurology, New England Journal of Medicine, and Headache.

Patients with migraine experienced about a 60% reduction in pain intensity and number of headache days per month after exposure to green light therapy, according to results of a small study from the University of Arizona, Tucson.

“This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, “ senior author Mohab M. Ibrahim, MD, PhD, said in a press release. “Now I have another tool in my toolbox to treat one of the most difficult neurologic conditions – migraine.”

“Given the safety, affordability, and efficacy of green light exposure, there is merit to conduct a larger study,” he and coauthors from the university wrote in their paper.

The study included 29 adult patients (average age 52.2 years), 22 with chronic migraine and the rest with episodic migraine who were recruited from the University of Arizona/Banner Medical Center chronic pain clinic. To be included, patients had to meet the International Headache Society diagnostic criteria for chronic or episodic migraine, have an average headache pain intensity of 5 out of 10 or greater on the numeric pain scale (NPS) over the 10 weeks prior to enrolling in the study, and be dissatisfied with their current migraine therapy.

The patients were free to start, continue, or discontinue any other migraine treatments as recommended by their physicians as long as this was reported to the study team.
 

White versus green

The one-way crossover design involved exposure to 10 weeks of white light emitting diodes, for 1-2 hours per day, followed by a 2-week washout period and then 10 weeks’ exposure to green light emitting diodes (GLED) for the same daily duration. The protocol involved use of a light strip emitting an intensity of between 4 and 100 lux measured at approximately 2 m and 1 m from a lux meter.

Patients were instructed to use the light in a dark room, without falling asleep, and to participate in activities that did not require external light sources, such as listening to music, reading books, doing exercises, or engaging in similar activities. The daily minimum exposure of 1 hour, up to a maximum of 2 hours, was to be completed in one sitting.

The primary outcome measure was the number of headache days per month, defined as days with moderate to severe headache pain for at least 4 hours. Secondary outcomes included perceived reduction in duration and intensity of the headache phase of the migraine episodes assessed every 2 weeks with the NPS, improved ability to fall and stay asleep, improved ability to perform work and daily activity, improved quality of life, and reduction of pain medications.

The researchers found that when the patients with chronic migraine and episodic migraine were examined as separate groups, white light exposure did not significantly reduce the number of headache days per month, but when the chronic migraine and episodic migraine groups were combined there was a significant reduction from 18.2 to 16.5 headache days per month.

On the other hand, green light did result in significantly reduced headache days both in the separate (from 7.9 to 2.4 days in the episodic migraine group and 22.3 to 9.4 days in the chronic migraine group) and combined groups (from 18.4 to 7.4 days).

“While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes,” the authors reported.

“The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them,” coauthor Amol M. Patwardhan, MD, PhD, said in the press release. “The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures,” said Dr. Patwardhan, associate professor and vice chair of research in the University of Arizona’s department of anesthesiology.
 

Better than white light

Asked to comment on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said research has shown for some time that exposure to green light has beneficial effects in migraine patients. This study, although small, does indicate that green light is more beneficial than is white light and reduces headache days and intensity. “I believe patients would be willing to spend 1-2 hours a day in green light to reduce and improve their migraine with few side effects. A larger randomized trial should be done,” he said.

The study was funded by support from the National Center for Complementary and Integrative Health (to Dr. Ibrahim), the Comprehensive Chronic Pain and Addiction Center–University of Arizona, and the University of Arizona CHiLLI initiative. Dr. Ibrahim and one coauthor have a patent pending through the University of Arizona for use of green light therapy for the management of chronic pain. Dr. Rapoport is a former president of the International Headache Society. He is an editor of Headache and CNS Drugs, and Editor-in-Chief of Neurology Reviews. He reviews for many peer-reviewed journals such as Cephalalgia, Neurology, New England Journal of Medicine, and Headache.

Patients with migraine experienced about a 60% reduction in pain intensity and number of headache days per month after exposure to green light therapy, according to results of a small study from the University of Arizona, Tucson.

“This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, “ senior author Mohab M. Ibrahim, MD, PhD, said in a press release. “Now I have another tool in my toolbox to treat one of the most difficult neurologic conditions – migraine.”

“Given the safety, affordability, and efficacy of green light exposure, there is merit to conduct a larger study,” he and coauthors from the university wrote in their paper.

The study included 29 adult patients (average age 52.2 years), 22 with chronic migraine and the rest with episodic migraine who were recruited from the University of Arizona/Banner Medical Center chronic pain clinic. To be included, patients had to meet the International Headache Society diagnostic criteria for chronic or episodic migraine, have an average headache pain intensity of 5 out of 10 or greater on the numeric pain scale (NPS) over the 10 weeks prior to enrolling in the study, and be dissatisfied with their current migraine therapy.

The patients were free to start, continue, or discontinue any other migraine treatments as recommended by their physicians as long as this was reported to the study team.
 

White versus green

The one-way crossover design involved exposure to 10 weeks of white light emitting diodes, for 1-2 hours per day, followed by a 2-week washout period and then 10 weeks’ exposure to green light emitting diodes (GLED) for the same daily duration. The protocol involved use of a light strip emitting an intensity of between 4 and 100 lux measured at approximately 2 m and 1 m from a lux meter.

Patients were instructed to use the light in a dark room, without falling asleep, and to participate in activities that did not require external light sources, such as listening to music, reading books, doing exercises, or engaging in similar activities. The daily minimum exposure of 1 hour, up to a maximum of 2 hours, was to be completed in one sitting.

The primary outcome measure was the number of headache days per month, defined as days with moderate to severe headache pain for at least 4 hours. Secondary outcomes included perceived reduction in duration and intensity of the headache phase of the migraine episodes assessed every 2 weeks with the NPS, improved ability to fall and stay asleep, improved ability to perform work and daily activity, improved quality of life, and reduction of pain medications.

The researchers found that when the patients with chronic migraine and episodic migraine were examined as separate groups, white light exposure did not significantly reduce the number of headache days per month, but when the chronic migraine and episodic migraine groups were combined there was a significant reduction from 18.2 to 16.5 headache days per month.

On the other hand, green light did result in significantly reduced headache days both in the separate (from 7.9 to 2.4 days in the episodic migraine group and 22.3 to 9.4 days in the chronic migraine group) and combined groups (from 18.4 to 7.4 days).

“While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes,” the authors reported.

“The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them,” coauthor Amol M. Patwardhan, MD, PhD, said in the press release. “The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures,” said Dr. Patwardhan, associate professor and vice chair of research in the University of Arizona’s department of anesthesiology.
 

Better than white light

Asked to comment on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said research has shown for some time that exposure to green light has beneficial effects in migraine patients. This study, although small, does indicate that green light is more beneficial than is white light and reduces headache days and intensity. “I believe patients would be willing to spend 1-2 hours a day in green light to reduce and improve their migraine with few side effects. A larger randomized trial should be done,” he said.

The study was funded by support from the National Center for Complementary and Integrative Health (to Dr. Ibrahim), the Comprehensive Chronic Pain and Addiction Center–University of Arizona, and the University of Arizona CHiLLI initiative. Dr. Ibrahim and one coauthor have a patent pending through the University of Arizona for use of green light therapy for the management of chronic pain. Dr. Rapoport is a former president of the International Headache Society. He is an editor of Headache and CNS Drugs, and Editor-in-Chief of Neurology Reviews. He reviews for many peer-reviewed journals such as Cephalalgia, Neurology, New England Journal of Medicine, and Headache.

A minimally invasive blood test along with artificial intelligence (AI) may flag early-stage Alzheimer’s disease, raising the prospect of early intervention when effective treatments become available.

In a study, investigators used six AI methodologies, including Deep Learning, to assess blood leukocyte epigenomic biomarkers. They found more than 150 genetic differences among study participants with Alzheimer’s disease in comparison with participants who did not have Alzheimer’s disease.

All of the AI platforms were effective in predicting Alzheimer’s disease. Deep Learning’s assessment of intragenic cytosine-phosphate-guanines (CpGs) had sensitivity and specificity rates of 97%.

“It’s almost as if the leukocytes have become a newspaper to tell us, ‘This is what is going on in the brain,’ “ lead author Ray Bahado-Singh, MD, chair of the department of obstetrics and gynecology, Oakland University, Auburn Hills, Mich., said in a news release.

The researchers noted that the findings, if replicated in future studies, may help in providing Alzheimer’s disease diagnoses “much earlier” in the disease process. “The holy grail is to identify patients in the preclinical stage so effective early interventions, including new medications, can be studied and ultimately used,” Dr. Bahado-Singh said.

“This certainly isn’t the final step in Alzheimer’s research, but I think this represents a significant change in direction,” he told attendees at a press briefing.

The findings were published online March 31 in PLOS ONE.
 

Silver tsunami

The investigators noted that Alzheimer’s disease is often diagnosed when the disease is in its later stages, after irreversible brain damage has occurred. “There is currently no cure for the disease, and the treatment is limited to drugs that attempt to treat symptoms and have little effect on the disease’s progression,” they noted.

Coinvestigator Khaled Imam, MD, director of geriatric medicine for Beaumont Health in Michigan, pointed out that although MRI and lumbar puncture can identify Alzheimer’s disease early on, the processes are expensive and/or invasive.

“Having biomarkers in the blood ... and being able to identify [Alzheimer’s disease] years before symptoms start, hopefully we’d be able to intervene early on in the process of the disease,” Dr. Imam said.

It is estimated that the number of Americans aged 85 and older will triple by 2050. This impending “silver tsunami,” which will come with a commensurate increase in Alzheimer’s disease cases, makes it even more important to be able to diagnose the disease early on, he noted.

The study included 24 individuals with late-onset Alzheimer’s disease (70.8% women; mean age, 83 years); 24 were deemed to be “cognitively healthy” (66.7% women; mean age, 80 years). About 500 ng of genomic DNA was extracted from whole-blood samples from each participant.

The researchers used the Infinium MethylationEPIC BeadChip array, and the samples were then examined for markers of methylation that would “indicate the disease process has started,” they noted.

In addition to Deep Learning, the five other AI platforms were the Support Vector Machine, Generalized Linear Model, Prediction Analysis for Microarrays, Random Forest, and Linear Discriminant Analysis.

These platforms were used to assess leukocyte genome changes. To predict Alzheimer’s disease, the researchers also used Ingenuity Pathway Analysis.
 

Significant “chemical changes”

Results showed that the Alzheimer’s disease group had 152 significantly differentially methylated CpGs in 171 genes in comparison with the non-Alzheimer’s disease group (false discovery rate P value < .05).

As a whole, using intragenic and intergenic/extragenic CpGs, the AI platforms were effective in predicting who had Alzheimer’s disease (area under the curve [AUC], ≥ 0.93). Using intragenic markers, the AUC for Deep Learning was 0.99.

“We looked at close to a million different sites, and we saw some chemical changes that we know are associated with alteration or change in gene function,” Dr. Bahado-Singh said.

Altered genes that were found in the Alzheimer’s disease group included CR1L, CTSV, S1PR1, and LTB4R – all of which “have been previously linked with Alzheimer’s disease and dementia,” the researchers noted. They also found the methylated genes CTSV and PRMT5, both of which have been previously associated with cardiovascular disease.

“A significant strength of our study is the novelty, i.e. the use of blood leukocytes to accurately detect Alzheimer’s disease and also for interrogating the pathogenesis of Alzheimer’s disease,” the investigators wrote.

Dr. Bahado-Singh said that the test let them identify changes in cells in the blood, “giving us a comprehensive account not only of the fact that the brain is being affected by Alzheimer’s disease but it’s telling us what kinds of processes are going on in the brain.

“Normally you don’t have access to the brain. This gives us a simple blood test to get an ongoing reading of the course of events in the brain – and potentially tell us very early on before the onset of symptoms,” he added.
 

Cautiously optimistic

During the question-and-answer session following his presentation at the briefing, Dr. Bahado-Singh reiterated that they are at a very early stage in the research and were not able to make clinical recommendations at this point. However, he added, “There was evidence that DNA methylation change could likely precede the onset of abnormalities in the cells that give rise to the disease.”

Coinvestigator Stewart Graham, PhD, director of Alzheimer’s research at Beaumont Health, added that although the initial study findings led to some excitement for the team, “we have to be very conservative with what we say.”

He noted that the findings need to be replicated in a more diverse population. Still, “we’re excited at the moment and looking forward to seeing what the future results hold,” Dr. Graham said.

Dr. Bahado-Singh said that if larger studies confirm the findings and the test is viable, it would make sense to use it as a screen for individuals older than 65. He noted that because of the aging of the population, “this subset of individuals will constitute a larger and larger fraction of the population globally.”
 

Still early days

Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that the investigators used an “interesting” diagnostic process.

“It was a unique approach to looking at and trying to understand what might be some of the biological underpinnings and using these tools and technologies to determine if they’re able to differentiate individuals with Alzheimer’s disease” from those without Alzheimer’s disease, said Dr. Snyder, who was not involved with the research.

“Ultimately, we want to know who is at greater risk, who may have some of the changing biology at the earliest time point so that we can intervene to stop the progression of the disease,” she said.

She pointed out that a number of types of biomarker tests are currently under investigation, many of which are measuring different outcomes. “And that’s what we want to see going forward. We want to have as many tools in our toolbox that allow us to accurately diagnose at that earliest time point,” Dr. Snyder said.

“At this point, [the current study] is still pretty early, so it needs to be replicated and then expanded to larger groups to really understand what they may be seeing,” she added.

Dr. Bahado-Singh, Dr. Imam, Dr. Graham, and Dr. Snyder have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A minimally invasive blood test along with artificial intelligence (AI) may flag early-stage Alzheimer’s disease, raising the prospect of early intervention when effective treatments become available.

In a study, investigators used six AI methodologies, including Deep Learning, to assess blood leukocyte epigenomic biomarkers. They found more than 150 genetic differences among study participants with Alzheimer’s disease in comparison with participants who did not have Alzheimer’s disease.

All of the AI platforms were effective in predicting Alzheimer’s disease. Deep Learning’s assessment of intragenic cytosine-phosphate-guanines (CpGs) had sensitivity and specificity rates of 97%.

“It’s almost as if the leukocytes have become a newspaper to tell us, ‘This is what is going on in the brain,’ “ lead author Ray Bahado-Singh, MD, chair of the department of obstetrics and gynecology, Oakland University, Auburn Hills, Mich., said in a news release.

The researchers noted that the findings, if replicated in future studies, may help in providing Alzheimer’s disease diagnoses “much earlier” in the disease process. “The holy grail is to identify patients in the preclinical stage so effective early interventions, including new medications, can be studied and ultimately used,” Dr. Bahado-Singh said.

“This certainly isn’t the final step in Alzheimer’s research, but I think this represents a significant change in direction,” he told attendees at a press briefing.

The findings were published online March 31 in PLOS ONE.
 

Silver tsunami

The investigators noted that Alzheimer’s disease is often diagnosed when the disease is in its later stages, after irreversible brain damage has occurred. “There is currently no cure for the disease, and the treatment is limited to drugs that attempt to treat symptoms and have little effect on the disease’s progression,” they noted.

Coinvestigator Khaled Imam, MD, director of geriatric medicine for Beaumont Health in Michigan, pointed out that although MRI and lumbar puncture can identify Alzheimer’s disease early on, the processes are expensive and/or invasive.

“Having biomarkers in the blood ... and being able to identify [Alzheimer’s disease] years before symptoms start, hopefully we’d be able to intervene early on in the process of the disease,” Dr. Imam said.

It is estimated that the number of Americans aged 85 and older will triple by 2050. This impending “silver tsunami,” which will come with a commensurate increase in Alzheimer’s disease cases, makes it even more important to be able to diagnose the disease early on, he noted.

The study included 24 individuals with late-onset Alzheimer’s disease (70.8% women; mean age, 83 years); 24 were deemed to be “cognitively healthy” (66.7% women; mean age, 80 years). About 500 ng of genomic DNA was extracted from whole-blood samples from each participant.

The researchers used the Infinium MethylationEPIC BeadChip array, and the samples were then examined for markers of methylation that would “indicate the disease process has started,” they noted.

In addition to Deep Learning, the five other AI platforms were the Support Vector Machine, Generalized Linear Model, Prediction Analysis for Microarrays, Random Forest, and Linear Discriminant Analysis.

These platforms were used to assess leukocyte genome changes. To predict Alzheimer’s disease, the researchers also used Ingenuity Pathway Analysis.
 

Significant “chemical changes”

Results showed that the Alzheimer’s disease group had 152 significantly differentially methylated CpGs in 171 genes in comparison with the non-Alzheimer’s disease group (false discovery rate P value < .05).

As a whole, using intragenic and intergenic/extragenic CpGs, the AI platforms were effective in predicting who had Alzheimer’s disease (area under the curve [AUC], ≥ 0.93). Using intragenic markers, the AUC for Deep Learning was 0.99.

“We looked at close to a million different sites, and we saw some chemical changes that we know are associated with alteration or change in gene function,” Dr. Bahado-Singh said.

Altered genes that were found in the Alzheimer’s disease group included CR1L, CTSV, S1PR1, and LTB4R – all of which “have been previously linked with Alzheimer’s disease and dementia,” the researchers noted. They also found the methylated genes CTSV and PRMT5, both of which have been previously associated with cardiovascular disease.

“A significant strength of our study is the novelty, i.e. the use of blood leukocytes to accurately detect Alzheimer’s disease and also for interrogating the pathogenesis of Alzheimer’s disease,” the investigators wrote.

Dr. Bahado-Singh said that the test let them identify changes in cells in the blood, “giving us a comprehensive account not only of the fact that the brain is being affected by Alzheimer’s disease but it’s telling us what kinds of processes are going on in the brain.

“Normally you don’t have access to the brain. This gives us a simple blood test to get an ongoing reading of the course of events in the brain – and potentially tell us very early on before the onset of symptoms,” he added.
 

Cautiously optimistic

During the question-and-answer session following his presentation at the briefing, Dr. Bahado-Singh reiterated that they are at a very early stage in the research and were not able to make clinical recommendations at this point. However, he added, “There was evidence that DNA methylation change could likely precede the onset of abnormalities in the cells that give rise to the disease.”

Coinvestigator Stewart Graham, PhD, director of Alzheimer’s research at Beaumont Health, added that although the initial study findings led to some excitement for the team, “we have to be very conservative with what we say.”

He noted that the findings need to be replicated in a more diverse population. Still, “we’re excited at the moment and looking forward to seeing what the future results hold,” Dr. Graham said.

Dr. Bahado-Singh said that if larger studies confirm the findings and the test is viable, it would make sense to use it as a screen for individuals older than 65. He noted that because of the aging of the population, “this subset of individuals will constitute a larger and larger fraction of the population globally.”
 

Still early days

Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that the investigators used an “interesting” diagnostic process.

“It was a unique approach to looking at and trying to understand what might be some of the biological underpinnings and using these tools and technologies to determine if they’re able to differentiate individuals with Alzheimer’s disease” from those without Alzheimer’s disease, said Dr. Snyder, who was not involved with the research.

“Ultimately, we want to know who is at greater risk, who may have some of the changing biology at the earliest time point so that we can intervene to stop the progression of the disease,” she said.

She pointed out that a number of types of biomarker tests are currently under investigation, many of which are measuring different outcomes. “And that’s what we want to see going forward. We want to have as many tools in our toolbox that allow us to accurately diagnose at that earliest time point,” Dr. Snyder said.

“At this point, [the current study] is still pretty early, so it needs to be replicated and then expanded to larger groups to really understand what they may be seeing,” she added.

Dr. Bahado-Singh, Dr. Imam, Dr. Graham, and Dr. Snyder have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A minimally invasive blood test along with artificial intelligence (AI) may flag early-stage Alzheimer’s disease, raising the prospect of early intervention when effective treatments become available.

In a study, investigators used six AI methodologies, including Deep Learning, to assess blood leukocyte epigenomic biomarkers. They found more than 150 genetic differences among study participants with Alzheimer’s disease in comparison with participants who did not have Alzheimer’s disease.

All of the AI platforms were effective in predicting Alzheimer’s disease. Deep Learning’s assessment of intragenic cytosine-phosphate-guanines (CpGs) had sensitivity and specificity rates of 97%.

“It’s almost as if the leukocytes have become a newspaper to tell us, ‘This is what is going on in the brain,’ “ lead author Ray Bahado-Singh, MD, chair of the department of obstetrics and gynecology, Oakland University, Auburn Hills, Mich., said in a news release.

The researchers noted that the findings, if replicated in future studies, may help in providing Alzheimer’s disease diagnoses “much earlier” in the disease process. “The holy grail is to identify patients in the preclinical stage so effective early interventions, including new medications, can be studied and ultimately used,” Dr. Bahado-Singh said.

“This certainly isn’t the final step in Alzheimer’s research, but I think this represents a significant change in direction,” he told attendees at a press briefing.

The findings were published online March 31 in PLOS ONE.
 

Silver tsunami

The investigators noted that Alzheimer’s disease is often diagnosed when the disease is in its later stages, after irreversible brain damage has occurred. “There is currently no cure for the disease, and the treatment is limited to drugs that attempt to treat symptoms and have little effect on the disease’s progression,” they noted.

Coinvestigator Khaled Imam, MD, director of geriatric medicine for Beaumont Health in Michigan, pointed out that although MRI and lumbar puncture can identify Alzheimer’s disease early on, the processes are expensive and/or invasive.

“Having biomarkers in the blood ... and being able to identify [Alzheimer’s disease] years before symptoms start, hopefully we’d be able to intervene early on in the process of the disease,” Dr. Imam said.

It is estimated that the number of Americans aged 85 and older will triple by 2050. This impending “silver tsunami,” which will come with a commensurate increase in Alzheimer’s disease cases, makes it even more important to be able to diagnose the disease early on, he noted.

The study included 24 individuals with late-onset Alzheimer’s disease (70.8% women; mean age, 83 years); 24 were deemed to be “cognitively healthy” (66.7% women; mean age, 80 years). About 500 ng of genomic DNA was extracted from whole-blood samples from each participant.

The researchers used the Infinium MethylationEPIC BeadChip array, and the samples were then examined for markers of methylation that would “indicate the disease process has started,” they noted.

In addition to Deep Learning, the five other AI platforms were the Support Vector Machine, Generalized Linear Model, Prediction Analysis for Microarrays, Random Forest, and Linear Discriminant Analysis.

These platforms were used to assess leukocyte genome changes. To predict Alzheimer’s disease, the researchers also used Ingenuity Pathway Analysis.
 

Significant “chemical changes”

Results showed that the Alzheimer’s disease group had 152 significantly differentially methylated CpGs in 171 genes in comparison with the non-Alzheimer’s disease group (false discovery rate P value < .05).

As a whole, using intragenic and intergenic/extragenic CpGs, the AI platforms were effective in predicting who had Alzheimer’s disease (area under the curve [AUC], ≥ 0.93). Using intragenic markers, the AUC for Deep Learning was 0.99.

“We looked at close to a million different sites, and we saw some chemical changes that we know are associated with alteration or change in gene function,” Dr. Bahado-Singh said.

Altered genes that were found in the Alzheimer’s disease group included CR1L, CTSV, S1PR1, and LTB4R – all of which “have been previously linked with Alzheimer’s disease and dementia,” the researchers noted. They also found the methylated genes CTSV and PRMT5, both of which have been previously associated with cardiovascular disease.

“A significant strength of our study is the novelty, i.e. the use of blood leukocytes to accurately detect Alzheimer’s disease and also for interrogating the pathogenesis of Alzheimer’s disease,” the investigators wrote.

Dr. Bahado-Singh said that the test let them identify changes in cells in the blood, “giving us a comprehensive account not only of the fact that the brain is being affected by Alzheimer’s disease but it’s telling us what kinds of processes are going on in the brain.

“Normally you don’t have access to the brain. This gives us a simple blood test to get an ongoing reading of the course of events in the brain – and potentially tell us very early on before the onset of symptoms,” he added.
 

Cautiously optimistic

During the question-and-answer session following his presentation at the briefing, Dr. Bahado-Singh reiterated that they are at a very early stage in the research and were not able to make clinical recommendations at this point. However, he added, “There was evidence that DNA methylation change could likely precede the onset of abnormalities in the cells that give rise to the disease.”

Coinvestigator Stewart Graham, PhD, director of Alzheimer’s research at Beaumont Health, added that although the initial study findings led to some excitement for the team, “we have to be very conservative with what we say.”

He noted that the findings need to be replicated in a more diverse population. Still, “we’re excited at the moment and looking forward to seeing what the future results hold,” Dr. Graham said.

Dr. Bahado-Singh said that if larger studies confirm the findings and the test is viable, it would make sense to use it as a screen for individuals older than 65. He noted that because of the aging of the population, “this subset of individuals will constitute a larger and larger fraction of the population globally.”
 

Still early days

Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that the investigators used an “interesting” diagnostic process.

“It was a unique approach to looking at and trying to understand what might be some of the biological underpinnings and using these tools and technologies to determine if they’re able to differentiate individuals with Alzheimer’s disease” from those without Alzheimer’s disease, said Dr. Snyder, who was not involved with the research.

“Ultimately, we want to know who is at greater risk, who may have some of the changing biology at the earliest time point so that we can intervene to stop the progression of the disease,” she said.

She pointed out that a number of types of biomarker tests are currently under investigation, many of which are measuring different outcomes. “And that’s what we want to see going forward. We want to have as many tools in our toolbox that allow us to accurately diagnose at that earliest time point,” Dr. Snyder said.

“At this point, [the current study] is still pretty early, so it needs to be replicated and then expanded to larger groups to really understand what they may be seeing,” she added.

Dr. Bahado-Singh, Dr. Imam, Dr. Graham, and Dr. Snyder have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.

Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.

Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.

References:

Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01.

Wei M, Wang X, Zimmerman DN, Burt LM, Haaland B, Henry NL. Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer. Breast Cancer Res Treat. 2021 Jan 9. doi: 10.1007/s10549-020-06071-w.Epub ahead of print.

Emens LA, Adams S, Barrios CH, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab plus nabpaclitaxel versus placebo plus nabpaclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: ESMO Virtual Congress 2020, Ann Oncol. 2020;31S:ESMO #LBA16.

Khan NAJ, Alsharedi M. Bullous Skin Rash: A Rare Case of Palbociclib-Induced Dermatological Toxicity. Cureus. 2020 Sep 3;12(9):e10229. doi: 10.7759/cureus.10229.

Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.

Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.

Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.

References:

Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01.

Wei M, Wang X, Zimmerman DN, Burt LM, Haaland B, Henry NL. Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer. Breast Cancer Res Treat. 2021 Jan 9. doi: 10.1007/s10549-020-06071-w.Epub ahead of print.

Emens LA, Adams S, Barrios CH, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab plus nabpaclitaxel versus placebo plus nabpaclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: ESMO Virtual Congress 2020, Ann Oncol. 2020;31S:ESMO #LBA16.

Khan NAJ, Alsharedi M. Bullous Skin Rash: A Rare Case of Palbociclib-Induced Dermatological Toxicity. Cureus. 2020 Sep 3;12(9):e10229. doi: 10.7759/cureus.10229.

Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.

Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.

Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.

References:

Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01.

Wei M, Wang X, Zimmerman DN, Burt LM, Haaland B, Henry NL. Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer. Breast Cancer Res Treat. 2021 Jan 9. doi: 10.1007/s10549-020-06071-w.Epub ahead of print.

Emens LA, Adams S, Barrios CH, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab plus nabpaclitaxel versus placebo plus nabpaclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: ESMO Virtual Congress 2020, Ann Oncol. 2020;31S:ESMO #LBA16.

Khan NAJ, Alsharedi M. Bullous Skin Rash: A Rare Case of Palbociclib-Induced Dermatological Toxicity. Cureus. 2020 Sep 3;12(9):e10229. doi: 10.7759/cureus.10229.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: In patients with newly diagnosed breast cancer (BC), the risk of local recurrence (LR) as a first event within 5 years of diagnosis was low and declined further with the number of event-free years.

Major finding: Overall, the incidence of LR as a first event within 5 years of diagnosis was 3.0%, which decreased to 2.4%, 1.6%, 1.0%, and 0.6% after 1, 2, 3, and 4 event-free years, respectively.

Study details: Findings are from the nationwide Netherlands Cancer Registry database, including 34,453 patients with newly diagnosed breast cancer between 2005 and 2008.

Disclosures: This study was supported by CZ fonds 201400316. ML Smidt reported receiving grant from Servier Pharma. Other authors had no disclosures.

Source: Moossdorff M et al. Breast Cancer Res Treat. 2021 Mar 10. doi: 10.1007/s10549-020-06040-3.

Key clinical point: In patients with newly diagnosed breast cancer (BC), the risk of local recurrence (LR) as a first event within 5 years of diagnosis was low and declined further with the number of event-free years.

Major finding: Overall, the incidence of LR as a first event within 5 years of diagnosis was 3.0%, which decreased to 2.4%, 1.6%, 1.0%, and 0.6% after 1, 2, 3, and 4 event-free years, respectively.

Study details: Findings are from the nationwide Netherlands Cancer Registry database, including 34,453 patients with newly diagnosed breast cancer between 2005 and 2008.

Disclosures: This study was supported by CZ fonds 201400316. ML Smidt reported receiving grant from Servier Pharma. Other authors had no disclosures.

Source: Moossdorff M et al. Breast Cancer Res Treat. 2021 Mar 10. doi: 10.1007/s10549-020-06040-3.

Key clinical point: In patients with newly diagnosed breast cancer (BC), the risk of local recurrence (LR) as a first event within 5 years of diagnosis was low and declined further with the number of event-free years.

Major finding: Overall, the incidence of LR as a first event within 5 years of diagnosis was 3.0%, which decreased to 2.4%, 1.6%, 1.0%, and 0.6% after 1, 2, 3, and 4 event-free years, respectively.

Study details: Findings are from the nationwide Netherlands Cancer Registry database, including 34,453 patients with newly diagnosed breast cancer between 2005 and 2008.

Disclosures: This study was supported by CZ fonds 201400316. ML Smidt reported receiving grant from Servier Pharma. Other authors had no disclosures.

Source: Moossdorff M et al. Breast Cancer Res Treat. 2021 Mar 10. doi: 10.1007/s10549-020-06040-3.

Key clinical point: Use of female hormones was associated with an increased incidence of breast cancer (BC) in premenopausal women. Among postmenopausal women, older age at first birth increased the incidence of BC, whereas more births decreased it.

Major finding: Use of female hormones significantly increased the incidence of premenopausal breast cancer (adjusted hazard ratio [aHR], 1.53; P = .03). Incidence of postmenopausal breast cancer was higher in women aged 26 years or more vs. 21-25 years at first birth (aHR, 1.34, 1.47, and 1.68 for ages 26-30, 31-35, and 36 years and older, respectively; P less than .001) and lower in women giving more vs. no births (aHR, 0.85, 0.65, and 0.52 for 1, 2, and 3 and more births, respectively; P = .02).

Study details: Findings are from a pooled analysis of 9 population-based cohort studies conducted in Japan including 187,999 women (premenopausal, n=61,113; postmenopausal, n=126,886).

Disclosures: This study was supported by the National Cancer Center Research and Development Fund and the Health and Labour Sciences Research Grants for the Third Term Comprehensive Control Research for Cancer. The authors had no disclosures.

Source: Takeuchi T et al. Cancer Med. 2021 Mar 1. doi: 10.1002/cam4.3752.

Key clinical point: Use of female hormones was associated with an increased incidence of breast cancer (BC) in premenopausal women. Among postmenopausal women, older age at first birth increased the incidence of BC, whereas more births decreased it.

Major finding: Use of female hormones significantly increased the incidence of premenopausal breast cancer (adjusted hazard ratio [aHR], 1.53; P = .03). Incidence of postmenopausal breast cancer was higher in women aged 26 years or more vs. 21-25 years at first birth (aHR, 1.34, 1.47, and 1.68 for ages 26-30, 31-35, and 36 years and older, respectively; P less than .001) and lower in women giving more vs. no births (aHR, 0.85, 0.65, and 0.52 for 1, 2, and 3 and more births, respectively; P = .02).

Study details: Findings are from a pooled analysis of 9 population-based cohort studies conducted in Japan including 187,999 women (premenopausal, n=61,113; postmenopausal, n=126,886).

Disclosures: This study was supported by the National Cancer Center Research and Development Fund and the Health and Labour Sciences Research Grants for the Third Term Comprehensive Control Research for Cancer. The authors had no disclosures.

Source: Takeuchi T et al. Cancer Med. 2021 Mar 1. doi: 10.1002/cam4.3752.

Key clinical point: Use of female hormones was associated with an increased incidence of breast cancer (BC) in premenopausal women. Among postmenopausal women, older age at first birth increased the incidence of BC, whereas more births decreased it.

Major finding: Use of female hormones significantly increased the incidence of premenopausal breast cancer (adjusted hazard ratio [aHR], 1.53; P = .03). Incidence of postmenopausal breast cancer was higher in women aged 26 years or more vs. 21-25 years at first birth (aHR, 1.34, 1.47, and 1.68 for ages 26-30, 31-35, and 36 years and older, respectively; P less than .001) and lower in women giving more vs. no births (aHR, 0.85, 0.65, and 0.52 for 1, 2, and 3 and more births, respectively; P = .02).

Study details: Findings are from a pooled analysis of 9 population-based cohort studies conducted in Japan including 187,999 women (premenopausal, n=61,113; postmenopausal, n=126,886).

Disclosures: This study was supported by the National Cancer Center Research and Development Fund and the Health and Labour Sciences Research Grants for the Third Term Comprehensive Control Research for Cancer. The authors had no disclosures.

Source: Takeuchi T et al. Cancer Med. 2021 Mar 1. doi: 10.1002/cam4.3752.

Key clinical point: Preoperative breast magnetic resonance imaging (MRI) has low accuracy in predicting nodal status after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), suggesting that axillary findings on posttreatment breast MRI should not be used to plan surgical approach to the axilla.

Major finding: Overall, the accuracy of posttreatment breast MRI in predicting axillary nodal status ranged from 45.5% to 66.7%. The overall accuracy of MRI for predicting nodal status was similar among patients treated with neoadjuvant endocrine therapy (ET) vs. chemotherapy (66.7% vs. 50%; P = .1393).

Study details: Findings are from a retrospective analysis of 79 women with stage I-III ILC who underwent preoperative breast MRI after either neoadjuvant chemotherapy (n=46) or ET (n=33).

Disclosures: This publication was supported by the National Center for Advancing Translational Sciences, National Institute of Health. The authors declared no conflicts of interest.

Source: Abel MK et al. NPJ Breast Cancer. 2021 Mar 5. doi: 10.1038/s41523-021-00233-9.

Key clinical point: Preoperative breast magnetic resonance imaging (MRI) has low accuracy in predicting nodal status after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), suggesting that axillary findings on posttreatment breast MRI should not be used to plan surgical approach to the axilla.

Major finding: Overall, the accuracy of posttreatment breast MRI in predicting axillary nodal status ranged from 45.5% to 66.7%. The overall accuracy of MRI for predicting nodal status was similar among patients treated with neoadjuvant endocrine therapy (ET) vs. chemotherapy (66.7% vs. 50%; P = .1393).

Study details: Findings are from a retrospective analysis of 79 women with stage I-III ILC who underwent preoperative breast MRI after either neoadjuvant chemotherapy (n=46) or ET (n=33).

Disclosures: This publication was supported by the National Center for Advancing Translational Sciences, National Institute of Health. The authors declared no conflicts of interest.

Source: Abel MK et al. NPJ Breast Cancer. 2021 Mar 5. doi: 10.1038/s41523-021-00233-9.

Key clinical point: Preoperative breast magnetic resonance imaging (MRI) has low accuracy in predicting nodal status after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), suggesting that axillary findings on posttreatment breast MRI should not be used to plan surgical approach to the axilla.

Major finding: Overall, the accuracy of posttreatment breast MRI in predicting axillary nodal status ranged from 45.5% to 66.7%. The overall accuracy of MRI for predicting nodal status was similar among patients treated with neoadjuvant endocrine therapy (ET) vs. chemotherapy (66.7% vs. 50%; P = .1393).

Study details: Findings are from a retrospective analysis of 79 women with stage I-III ILC who underwent preoperative breast MRI after either neoadjuvant chemotherapy (n=46) or ET (n=33).

Disclosures: This publication was supported by the National Center for Advancing Translational Sciences, National Institute of Health. The authors declared no conflicts of interest.

Source: Abel MK et al. NPJ Breast Cancer. 2021 Mar 5. doi: 10.1038/s41523-021-00233-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.