Michele G. Sullivan

The Food and Drug Administration has approved a minimally invasive angioplasty system that enters the carotid artery adjacent to a blockage, and captures embolic debris by extracorporeal filtration of blood near the blockage.

The ENROUTE Transcarotid Neuroprotection System (ENROUTE TNS) is inserted into the artery near the stenotic region. As the stent is deployed, the system draws blood down the tube, away from the brain, under high pressure. An extracorporeal filter traps any emboli, and the filtered blood is returned via the femoral vein.

ENROUTE TNS was approved on the basis of the successful ROADSTER trial (Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure). In this study, there was a 3.5% rate of stroke, heart attack, and death among patients treated with the device – significantly lower than the study’s primary outcome goal of 11%. The rate of adverse events was about 14%; these included excessive bleeding or injury at the device insertion site, hypotension, and thrombosis.

The system’s benefits include its minimally invasive approach and the ability to successfully navigate severe carotid tortuosity. It also may be more successful than traditional arterial angioplasty for patients with difficult anatomy of the aortic arch, according to an FDA statement.

Manufactured by Silk Road, Sunnyvale, Calif., the ENROUTE TNS device was approved through a 510(k) submission, which provides an approval pathway for low- to moderate-risk devices that are substantially equivalent to a legally marketed device. According to the FDA statement, ENROUTE TNS is equivalent to a currently marketed flow-reversal system that uses similar technology and has the same intended use, but is designed to be introduced through the groin.

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On Twitter @alz_gal

The Food and Drug Administration has approved a minimally invasive angioplasty system that enters the carotid artery adjacent to a blockage, and captures embolic debris by extracorporeal filtration of blood near the blockage.

The ENROUTE Transcarotid Neuroprotection System (ENROUTE TNS) is inserted into the artery near the stenotic region. As the stent is deployed, the system draws blood down the tube, away from the brain, under high pressure. An extracorporeal filter traps any emboli, and the filtered blood is returned via the femoral vein.

ENROUTE TNS was approved on the basis of the successful ROADSTER trial (Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure). In this study, there was a 3.5% rate of stroke, heart attack, and death among patients treated with the device – significantly lower than the study’s primary outcome goal of 11%. The rate of adverse events was about 14%; these included excessive bleeding or injury at the device insertion site, hypotension, and thrombosis.

The system’s benefits include its minimally invasive approach and the ability to successfully navigate severe carotid tortuosity. It also may be more successful than traditional arterial angioplasty for patients with difficult anatomy of the aortic arch, according to an FDA statement.

Manufactured by Silk Road, Sunnyvale, Calif., the ENROUTE TNS device was approved through a 510(k) submission, which provides an approval pathway for low- to moderate-risk devices that are substantially equivalent to a legally marketed device. According to the FDA statement, ENROUTE TNS is equivalent to a currently marketed flow-reversal system that uses similar technology and has the same intended use, but is designed to be introduced through the groin.

[email protected]

On Twitter @alz_gal

The Food and Drug Administration has approved a minimally invasive angioplasty system that enters the carotid artery adjacent to a blockage, and captures embolic debris by extracorporeal filtration of blood near the blockage.

The ENROUTE Transcarotid Neuroprotection System (ENROUTE TNS) is inserted into the artery near the stenotic region. As the stent is deployed, the system draws blood down the tube, away from the brain, under high pressure. An extracorporeal filter traps any emboli, and the filtered blood is returned via the femoral vein.

ENROUTE TNS was approved on the basis of the successful ROADSTER trial (Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure). In this study, there was a 3.5% rate of stroke, heart attack, and death among patients treated with the device – significantly lower than the study’s primary outcome goal of 11%. The rate of adverse events was about 14%; these included excessive bleeding or injury at the device insertion site, hypotension, and thrombosis.

The system’s benefits include its minimally invasive approach and the ability to successfully navigate severe carotid tortuosity. It also may be more successful than traditional arterial angioplasty for patients with difficult anatomy of the aortic arch, according to an FDA statement.

Manufactured by Silk Road, Sunnyvale, Calif., the ENROUTE TNS device was approved through a 510(k) submission, which provides an approval pathway for low- to moderate-risk devices that are substantially equivalent to a legally marketed device. According to the FDA statement, ENROUTE TNS is equivalent to a currently marketed flow-reversal system that uses similar technology and has the same intended use, but is designed to be introduced through the groin.

[email protected]

On Twitter @alz_gal

Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes by 3 months, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium trial published in the Feb. 5 issue of the New England Journal of Medicine.

The drug did not shift functional outcomes in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.

At 3 months, a little more than half of each group had an modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).

The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions en route to a hospital. In a number of animal models of stroke, magnesium sulfate has been shown to exert both “vasodilatory and direct neuroprotective and glioprotective effects,” the investigators wrote.

It’s unclear why FAST-MAG didn’t replicate these earlier findings, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors. Slow transport of magnesium into the brain could be a contributing factor.

“Magnesium trafficking across the blood-brain barrier is not immediate. The concentration of magnesium in the cerebrospinal fluid peaks 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Magnesium sulfate may not have accumulated in brain tissues quickly enough to yield a benefit despite rapid attainment of increased serum levels,” they wrote.

The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study.

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On Twitter @alz_gal

Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes by 3 months, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium trial published in the Feb. 5 issue of the New England Journal of Medicine.

The drug did not shift functional outcomes in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.

At 3 months, a little more than half of each group had an modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).

The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions en route to a hospital. In a number of animal models of stroke, magnesium sulfate has been shown to exert both “vasodilatory and direct neuroprotective and glioprotective effects,” the investigators wrote.

It’s unclear why FAST-MAG didn’t replicate these earlier findings, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors. Slow transport of magnesium into the brain could be a contributing factor.

“Magnesium trafficking across the blood-brain barrier is not immediate. The concentration of magnesium in the cerebrospinal fluid peaks 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Magnesium sulfate may not have accumulated in brain tissues quickly enough to yield a benefit despite rapid attainment of increased serum levels,” they wrote.

The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study.

[email protected]

On Twitter @alz_gal

Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes by 3 months, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium trial published in the Feb. 5 issue of the New England Journal of Medicine.

The drug did not shift functional outcomes in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.

At 3 months, a little more than half of each group had an modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).

The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions en route to a hospital. In a number of animal models of stroke, magnesium sulfate has been shown to exert both “vasodilatory and direct neuroprotective and glioprotective effects,” the investigators wrote.

It’s unclear why FAST-MAG didn’t replicate these earlier findings, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors. Slow transport of magnesium into the brain could be a contributing factor.

“Magnesium trafficking across the blood-brain barrier is not immediate. The concentration of magnesium in the cerebrospinal fluid peaks 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Magnesium sulfate may not have accumulated in brain tissues quickly enough to yield a benefit despite rapid attainment of increased serum levels,” they wrote.

The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study.

[email protected]

On Twitter @alz_gal

Patients with advanced dementia should have increased access to comprehensive care wherever they live, including the facilities in which they spend the last months of their lives, a federal health care advisory panel has recommended.

Advanced care planning, palliative care, and increased access to hospice admission all would improve the quality of life for both patients and families, Dr. Laurel Coleman said at a meeting of the Advisory Council on Alzheimer’s Research, Care, and Services. Despite their proven benefits, however, these strategies aren’t universally available.

© Lighthaunter/Thinkstock

“Palliative care and hospice admission, for example, are both tools that make it much less likely that people with advanced dementia will die in a hospital, “ said Dr. Coleman, chair of the council’s clinical research and care subcommittee, which made the recommendations. “They have lower levels of pain and distress, and are less likely to have feeding tubes and restraints and other invasive measures implemented during the final stages of life.”

Hospice accessibility “is what keeps us up at night,” she said. Prognostication of life expectancy is difficult in advanced dementia, and hospice units typically only admit patients expected to live less than 6 months.

Other problems that impede appropriate hospice admission for these patients include incorrect coding – frailty instead of advanced dementia, for example – and the unintended consequences of new policies designed to restrict fraud and long-term hospital stays, said Dr. Coleman, a geriatrician at Maine Medical Center in Portland and a member of the palliative care team at Central Maine Medical Center in Lewiston. “Some of these things just make it unnecessarily hard for these patents to enter hospice.”

Because advanced dementia care is so fragmented, the majority of patients in the United States don’t get optimal care. “It’s really a case of luck – being at the right place in the right time. And if you’re not, you’re out of luck,” she noted.

Ideally, the federal government would support programs that care for dementia patients across the spectrum of their illness, said Dr. Coleman and her cochair, Dr. Susan Mitchell. They held up the Beatitudes Campus of Glendale, Ariz., as a prime example of what could be done to accommodate dementia patients and their families in a holistic setting that supports everyone throughout the course of the disease. The early memory program focuses on cognitively stimulating activities and full medical support that increases as needed. There is an emphasis on preempting disruptive behavior rather than responding to it after it develops. The advanced dementia care unit steps up all these goals as disease progresses.

Another unique aspect of the facility is its research arm and a full professional education program, said Dr. Mitchell, a geriatrician and director of palliative care research at the Institute for Aging Research, Boston. This focuses on building clinicians’ expertise in caring for dementia patients, preparing them to take on leadership roles in the field.

However, she said, “this is a highly aspirational goal. Implementing units like these [with federal support] will be like parting the Red Sea: Important, but extremely difficult.”

Despite the perhaps pie-in-the-sky goal, the subcommittee recommended that the Department of Health & Human Services pursue the idea of creating pilot “dementia-friendly communities” that would serve patients from diagnosis to death. “HHS should support a piloting process of 10-15 communities” that would be funded by a request for proposals from communities interested in participating. Ideally, these facilities would reflect diversity in culture and be split between rural and urban locales.

“Should the evaluation of the pilot programs justify replication, then the goal would be widespread adoption of dementia-friendly communities by 2020,” the committee noted.

As members of a federal working group, Dr. Coleman and Dr. Mitchell had no financial disclosures.

[email protected]

On Twitter @alz_gal

Patients with advanced dementia should have increased access to comprehensive care wherever they live, including the facilities in which they spend the last months of their lives, a federal health care advisory panel has recommended.

Advanced care planning, palliative care, and increased access to hospice admission all would improve the quality of life for both patients and families, Dr. Laurel Coleman said at a meeting of the Advisory Council on Alzheimer’s Research, Care, and Services. Despite their proven benefits, however, these strategies aren’t universally available.

© Lighthaunter/Thinkstock

“Palliative care and hospice admission, for example, are both tools that make it much less likely that people with advanced dementia will die in a hospital, “ said Dr. Coleman, chair of the council’s clinical research and care subcommittee, which made the recommendations. “They have lower levels of pain and distress, and are less likely to have feeding tubes and restraints and other invasive measures implemented during the final stages of life.”

Hospice accessibility “is what keeps us up at night,” she said. Prognostication of life expectancy is difficult in advanced dementia, and hospice units typically only admit patients expected to live less than 6 months.

Other problems that impede appropriate hospice admission for these patients include incorrect coding – frailty instead of advanced dementia, for example – and the unintended consequences of new policies designed to restrict fraud and long-term hospital stays, said Dr. Coleman, a geriatrician at Maine Medical Center in Portland and a member of the palliative care team at Central Maine Medical Center in Lewiston. “Some of these things just make it unnecessarily hard for these patents to enter hospice.”

Because advanced dementia care is so fragmented, the majority of patients in the United States don’t get optimal care. “It’s really a case of luck – being at the right place in the right time. And if you’re not, you’re out of luck,” she noted.

Ideally, the federal government would support programs that care for dementia patients across the spectrum of their illness, said Dr. Coleman and her cochair, Dr. Susan Mitchell. They held up the Beatitudes Campus of Glendale, Ariz., as a prime example of what could be done to accommodate dementia patients and their families in a holistic setting that supports everyone throughout the course of the disease. The early memory program focuses on cognitively stimulating activities and full medical support that increases as needed. There is an emphasis on preempting disruptive behavior rather than responding to it after it develops. The advanced dementia care unit steps up all these goals as disease progresses.

Another unique aspect of the facility is its research arm and a full professional education program, said Dr. Mitchell, a geriatrician and director of palliative care research at the Institute for Aging Research, Boston. This focuses on building clinicians’ expertise in caring for dementia patients, preparing them to take on leadership roles in the field.

However, she said, “this is a highly aspirational goal. Implementing units like these [with federal support] will be like parting the Red Sea: Important, but extremely difficult.”

Despite the perhaps pie-in-the-sky goal, the subcommittee recommended that the Department of Health & Human Services pursue the idea of creating pilot “dementia-friendly communities” that would serve patients from diagnosis to death. “HHS should support a piloting process of 10-15 communities” that would be funded by a request for proposals from communities interested in participating. Ideally, these facilities would reflect diversity in culture and be split between rural and urban locales.

“Should the evaluation of the pilot programs justify replication, then the goal would be widespread adoption of dementia-friendly communities by 2020,” the committee noted.

As members of a federal working group, Dr. Coleman and Dr. Mitchell had no financial disclosures.

[email protected]

On Twitter @alz_gal

Patients with advanced dementia should have increased access to comprehensive care wherever they live, including the facilities in which they spend the last months of their lives, a federal health care advisory panel has recommended.

Advanced care planning, palliative care, and increased access to hospice admission all would improve the quality of life for both patients and families, Dr. Laurel Coleman said at a meeting of the Advisory Council on Alzheimer’s Research, Care, and Services. Despite their proven benefits, however, these strategies aren’t universally available.

© Lighthaunter/Thinkstock

“Palliative care and hospice admission, for example, are both tools that make it much less likely that people with advanced dementia will die in a hospital, “ said Dr. Coleman, chair of the council’s clinical research and care subcommittee, which made the recommendations. “They have lower levels of pain and distress, and are less likely to have feeding tubes and restraints and other invasive measures implemented during the final stages of life.”

Hospice accessibility “is what keeps us up at night,” she said. Prognostication of life expectancy is difficult in advanced dementia, and hospice units typically only admit patients expected to live less than 6 months.

Other problems that impede appropriate hospice admission for these patients include incorrect coding – frailty instead of advanced dementia, for example – and the unintended consequences of new policies designed to restrict fraud and long-term hospital stays, said Dr. Coleman, a geriatrician at Maine Medical Center in Portland and a member of the palliative care team at Central Maine Medical Center in Lewiston. “Some of these things just make it unnecessarily hard for these patents to enter hospice.”

Because advanced dementia care is so fragmented, the majority of patients in the United States don’t get optimal care. “It’s really a case of luck – being at the right place in the right time. And if you’re not, you’re out of luck,” she noted.

Ideally, the federal government would support programs that care for dementia patients across the spectrum of their illness, said Dr. Coleman and her cochair, Dr. Susan Mitchell. They held up the Beatitudes Campus of Glendale, Ariz., as a prime example of what could be done to accommodate dementia patients and their families in a holistic setting that supports everyone throughout the course of the disease. The early memory program focuses on cognitively stimulating activities and full medical support that increases as needed. There is an emphasis on preempting disruptive behavior rather than responding to it after it develops. The advanced dementia care unit steps up all these goals as disease progresses.

Another unique aspect of the facility is its research arm and a full professional education program, said Dr. Mitchell, a geriatrician and director of palliative care research at the Institute for Aging Research, Boston. This focuses on building clinicians’ expertise in caring for dementia patients, preparing them to take on leadership roles in the field.

However, she said, “this is a highly aspirational goal. Implementing units like these [with federal support] will be like parting the Red Sea: Important, but extremely difficult.”

Despite the perhaps pie-in-the-sky goal, the subcommittee recommended that the Department of Health & Human Services pursue the idea of creating pilot “dementia-friendly communities” that would serve patients from diagnosis to death. “HHS should support a piloting process of 10-15 communities” that would be funded by a request for proposals from communities interested in participating. Ideally, these facilities would reflect diversity in culture and be split between rural and urban locales.

“Should the evaluation of the pilot programs justify replication, then the goal would be widespread adoption of dementia-friendly communities by 2020,” the committee noted.

As members of a federal working group, Dr. Coleman and Dr. Mitchell had no financial disclosures.

[email protected]

On Twitter @alz_gal

PHILADELPHIA – In patients with atrial fibrillation, declining kidney function significantly increased the risk of a major bleed during the first 30 days of warfarin therapy.

Those with the poorest kidney function had an 11-fold increase in the risk of a major bleed during that time, Min Jun, Ph.D., said at a meeting sponsored by the American Society of Nephrology. “After 30 days, the risk was attenuated, but it was still doubled,” compared with that of patients with normal kidney function.

Dr. Jun, a researcher at the University of Calgary (Alta.) retrospectively assessed bleeding incidence among 12,400 older adults with atrial fibrillation who started warfarin therapy from 2003 to 2010. He divided the cohort into six groups according to estimated glomerular filtration rates (eGFR), from normal (90 or more mL/min per 1.73 m²), to extremely poor (less than 15 mL/min per 1.73 m²).

The primary outcome was incident major bleeding (intracerebral, upper or lower gastrointestinal, or any other location). The analysis controlled for comorbidities, antiplatelet and nonsteroidal anti-inflammatory medications, and socioeconomic factors.

Almost 12% of the cohort experienced the primary outcome. The adjusted bleeding rates were highest for those with an eGFR of less than 15 mL/min per 1.73 m² (66 per 100 person-years) and lowest for those with an eGFR of at least 90 mL/min per 1.73 m² (5.9 per 100 person-years).

The rates moderated after the first 30 days of treatment, from 3.7 per 100 person-years in the highest eGFR group to 7.9 per 100 person-years in the lowest. But that was still a significant between-group difference.

The incidence ratio showed a clear, linear association with decreasing kidney function. During the first 30 days, it was highest in those patients with the lowest eGFR (11.08, compared with those with the highest eGFR). After 30 days, the ratio moderated; but it remained significantly elevated, compared with patients with the highest eGFR, at 2.09.

Kidney function apparently also influenced gastrointestinal bleeding, Dr. Jun noted. GI bleeding occurred in about 6% of those patients with an eGFR of at least 90 mL/min per 1.73 m², but in almost 19% of patients with an eGFR of less than 15 mL/min per 1.73 m². Intracranial bleeds occurred in less than 1% of patients in each group. There were no significant findings in other bleeding types, which were increased in the first 30 days of treatment, but which never exceeded 5% in any group.

Dr. Jun had no financial disclosures.

[email protected]

PHILADELPHIA – In patients with atrial fibrillation, declining kidney function significantly increased the risk of a major bleed during the first 30 days of warfarin therapy.

Those with the poorest kidney function had an 11-fold increase in the risk of a major bleed during that time, Min Jun, Ph.D., said at a meeting sponsored by the American Society of Nephrology. “After 30 days, the risk was attenuated, but it was still doubled,” compared with that of patients with normal kidney function.

Dr. Jun, a researcher at the University of Calgary (Alta.) retrospectively assessed bleeding incidence among 12,400 older adults with atrial fibrillation who started warfarin therapy from 2003 to 2010. He divided the cohort into six groups according to estimated glomerular filtration rates (eGFR), from normal (90 or more mL/min per 1.73 m²), to extremely poor (less than 15 mL/min per 1.73 m²).

The primary outcome was incident major bleeding (intracerebral, upper or lower gastrointestinal, or any other location). The analysis controlled for comorbidities, antiplatelet and nonsteroidal anti-inflammatory medications, and socioeconomic factors.

Almost 12% of the cohort experienced the primary outcome. The adjusted bleeding rates were highest for those with an eGFR of less than 15 mL/min per 1.73 m² (66 per 100 person-years) and lowest for those with an eGFR of at least 90 mL/min per 1.73 m² (5.9 per 100 person-years).

The rates moderated after the first 30 days of treatment, from 3.7 per 100 person-years in the highest eGFR group to 7.9 per 100 person-years in the lowest. But that was still a significant between-group difference.

The incidence ratio showed a clear, linear association with decreasing kidney function. During the first 30 days, it was highest in those patients with the lowest eGFR (11.08, compared with those with the highest eGFR). After 30 days, the ratio moderated; but it remained significantly elevated, compared with patients with the highest eGFR, at 2.09.

Kidney function apparently also influenced gastrointestinal bleeding, Dr. Jun noted. GI bleeding occurred in about 6% of those patients with an eGFR of at least 90 mL/min per 1.73 m², but in almost 19% of patients with an eGFR of less than 15 mL/min per 1.73 m². Intracranial bleeds occurred in less than 1% of patients in each group. There were no significant findings in other bleeding types, which were increased in the first 30 days of treatment, but which never exceeded 5% in any group.

Dr. Jun had no financial disclosures.

[email protected]

PHILADELPHIA – In patients with atrial fibrillation, declining kidney function significantly increased the risk of a major bleed during the first 30 days of warfarin therapy.

Those with the poorest kidney function had an 11-fold increase in the risk of a major bleed during that time, Min Jun, Ph.D., said at a meeting sponsored by the American Society of Nephrology. “After 30 days, the risk was attenuated, but it was still doubled,” compared with that of patients with normal kidney function.

Dr. Jun, a researcher at the University of Calgary (Alta.) retrospectively assessed bleeding incidence among 12,400 older adults with atrial fibrillation who started warfarin therapy from 2003 to 2010. He divided the cohort into six groups according to estimated glomerular filtration rates (eGFR), from normal (90 or more mL/min per 1.73 m²), to extremely poor (less than 15 mL/min per 1.73 m²).

The primary outcome was incident major bleeding (intracerebral, upper or lower gastrointestinal, or any other location). The analysis controlled for comorbidities, antiplatelet and nonsteroidal anti-inflammatory medications, and socioeconomic factors.

Almost 12% of the cohort experienced the primary outcome. The adjusted bleeding rates were highest for those with an eGFR of less than 15 mL/min per 1.73 m² (66 per 100 person-years) and lowest for those with an eGFR of at least 90 mL/min per 1.73 m² (5.9 per 100 person-years).

The rates moderated after the first 30 days of treatment, from 3.7 per 100 person-years in the highest eGFR group to 7.9 per 100 person-years in the lowest. But that was still a significant between-group difference.

The incidence ratio showed a clear, linear association with decreasing kidney function. During the first 30 days, it was highest in those patients with the lowest eGFR (11.08, compared with those with the highest eGFR). After 30 days, the ratio moderated; but it remained significantly elevated, compared with patients with the highest eGFR, at 2.09.

Kidney function apparently also influenced gastrointestinal bleeding, Dr. Jun noted. GI bleeding occurred in about 6% of those patients with an eGFR of at least 90 mL/min per 1.73 m², but in almost 19% of patients with an eGFR of less than 15 mL/min per 1.73 m². Intracranial bleeds occurred in less than 1% of patients in each group. There were no significant findings in other bleeding types, which were increased in the first 30 days of treatment, but which never exceeded 5% in any group.

Dr. Jun had no financial disclosures.

[email protected]

PHILADELPHIA – Leuprolide acetate, in combination with an acetylcholinesterase inhibitor, helped to preserve cognitive function in Alzheimer’s disease patients in an exploratory study.

The study is small and the results are modest. But they do warrant further investigation in a larger group, Dr. Richard L. Bowen said at the Clinical Trials Conference on Alzheimer’s Disease.

Leuprolide acetate is an agonist of gonadotropin-releasing hormone (GnRH). Dr. Bowen, a family physician in Charleston, S.C., has long postulated that luteinizing hormone, which is highly present in Alzheimer’s brains – especially in the hippocampus – predisposes to cognitive decline. Some preclinical evidence exists to support the idea that luteinizing hormone may modulate amyloid precursor processing predisposing to amyloid plaque formation. Leuprolide’s effect of indirectly down-regulating the secretion of luteinizing hormone by desensitizing GnRH receptors improved cognition in a mouse model of Alzheimer’s, Dr. Bowen noted.

But it was actually a conversation about an Alzheimer’s patent with prostate cancer that sparked his 10-year work on leuprolide. “As a family practice physician, I was doing an annual exam on a postmenopausal woman, talking about the risks and benefits of hormone replacement therapy. She mentioned that her husband, who had Alzheimer’s, had been getting ‘some kind of hormone therapy’ for his prostate cancer. And she said very specifically that since he’d been on it he had not gotten any worse, and in fact, had improved a little,” he said in an interview.

This started Dr. Bowen to thinking about the relationship between gonadotropin suppression and its possible link to neurons and cognition. “Gonadotropins are very important in cell division and very high in fetal life – obviously important for fetal development, when you do want lots of cell division.”

Estrogen and testosterone eventually take center stage in human life, effectively shutting down gonadotropin production – for a while, at least. But when estrogen levels fall at menopause, gonadotropins rise again. “This could predispose terminally differentiated neurons – which aren’t supposed to divide – to cell division, thus, death.”

His theory holds that such a process could also increase amyloid burden. “This does seem to pan out in cellular and animal models, where the expression of gonadotropins in the brain perfectly correlates with amyloid deposition. It’s a coherent model of this disease that speaks to why and when we develop it.”

In 2004, Dr. Bowen and his colleagues published a paperdemonstrating that neuroblastoma cells exposed to luteinizing hormone showed a significant increase in amyloid precursor protein and a resultant increase in amyloidogenic processing.

That same paper found that leuprolide treatment in an ovariectomized Alzheimer’s mouse model decreased amyloid expression, suggesting that luteinizing hormone, not estrogen, drove the change.

At the meeting, he reported a 48-week, dose-ranging study of 109 women with mild to moderate Alzheimer’s. They received either placebo or leuprolide acetate injections with a low dose (11.25 mg) or high dose (22.5 mg), which were carried out over 12 weeks, with cognitive assessments conducted at regular intervals during the remainder of the study.

The primary endpoints were scores on the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC). Secondary endpoints included the Neuropsychiatric Inventory, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Burden Interview, and ADCS-CGI Severity Rating.

There were no significant between-group differences in the ADAS-cog or the ADCS-CGIC scores in the entire group. But a preplanned subgroup analysis turned up an intriguing finding in the 78 patients who were also taking an acetylcholinesterase inhibitor (AChEI).

Although they didn’t improve cognitively, patients taking the combination of an AChEI and leuprolide held their scores at baseline level in the ADAS-cog and ADCS-CGIC throughout the 36-week follow-up period. At 48 weeks, mean ADAS-cog score declined by 3.3 in the placebo group, 4.1 in the low-dose combination group, and 0.18 in the high-dose combination group.

Results were similarly significant on the ADCS-CGIC measure, with mean declines of 63% and 82% in the placebo and low-dose groups, respectively, compared with a 38% decline in the high-dose group.

The subgroup analysis found no differences on the other measures.

Dr. Bowen said the results of his study are even more intriguing when viewed in light of a studypublished by investigators at the Dana Farber Cancer Institute that showed a 50% reduction in Alzheimer’s incidence in men who had received leuprolide for prostate cancer.

“This was remarkably similar to what we saw in our own 12-year Medicare database review,” which examined incident Alzheimer’s after prostate cancer, gallbladder surgery, hernia repair, and enlarged prostate. “Again, the decrease in the risk of developing Alzheimer’s associated with prostate cancer was about 50%.”

Dr. Bowen noted that his data are about 10 years old now. He holds a soon-to-expire patent on the use of leuprolide for Alzheimer’s and was pursuing that with a corporation. However, the company fell apart and he said he has become free to share the information only now.

But the data are enough for him to be using the treatment on at least a few patients. “I have about five or six people, both men and women, who are taking it in combination with an AChEI. The families are very happy with what they see, and I’m hoping we can get the word out so we can accumulate more data on it.”

[email protected]

On Twitter @alz_gal

PHILADELPHIA – Leuprolide acetate, in combination with an acetylcholinesterase inhibitor, helped to preserve cognitive function in Alzheimer’s disease patients in an exploratory study.

The study is small and the results are modest. But they do warrant further investigation in a larger group, Dr. Richard L. Bowen said at the Clinical Trials Conference on Alzheimer’s Disease.

Leuprolide acetate is an agonist of gonadotropin-releasing hormone (GnRH). Dr. Bowen, a family physician in Charleston, S.C., has long postulated that luteinizing hormone, which is highly present in Alzheimer’s brains – especially in the hippocampus – predisposes to cognitive decline. Some preclinical evidence exists to support the idea that luteinizing hormone may modulate amyloid precursor processing predisposing to amyloid plaque formation. Leuprolide’s effect of indirectly down-regulating the secretion of luteinizing hormone by desensitizing GnRH receptors improved cognition in a mouse model of Alzheimer’s, Dr. Bowen noted.

But it was actually a conversation about an Alzheimer’s patent with prostate cancer that sparked his 10-year work on leuprolide. “As a family practice physician, I was doing an annual exam on a postmenopausal woman, talking about the risks and benefits of hormone replacement therapy. She mentioned that her husband, who had Alzheimer’s, had been getting ‘some kind of hormone therapy’ for his prostate cancer. And she said very specifically that since he’d been on it he had not gotten any worse, and in fact, had improved a little,” he said in an interview.

This started Dr. Bowen to thinking about the relationship between gonadotropin suppression and its possible link to neurons and cognition. “Gonadotropins are very important in cell division and very high in fetal life – obviously important for fetal development, when you do want lots of cell division.”

Estrogen and testosterone eventually take center stage in human life, effectively shutting down gonadotropin production – for a while, at least. But when estrogen levels fall at menopause, gonadotropins rise again. “This could predispose terminally differentiated neurons – which aren’t supposed to divide – to cell division, thus, death.”

His theory holds that such a process could also increase amyloid burden. “This does seem to pan out in cellular and animal models, where the expression of gonadotropins in the brain perfectly correlates with amyloid deposition. It’s a coherent model of this disease that speaks to why and when we develop it.”

In 2004, Dr. Bowen and his colleagues published a paperdemonstrating that neuroblastoma cells exposed to luteinizing hormone showed a significant increase in amyloid precursor protein and a resultant increase in amyloidogenic processing.

That same paper found that leuprolide treatment in an ovariectomized Alzheimer’s mouse model decreased amyloid expression, suggesting that luteinizing hormone, not estrogen, drove the change.

At the meeting, he reported a 48-week, dose-ranging study of 109 women with mild to moderate Alzheimer’s. They received either placebo or leuprolide acetate injections with a low dose (11.25 mg) or high dose (22.5 mg), which were carried out over 12 weeks, with cognitive assessments conducted at regular intervals during the remainder of the study.

The primary endpoints were scores on the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC). Secondary endpoints included the Neuropsychiatric Inventory, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Burden Interview, and ADCS-CGI Severity Rating.

There were no significant between-group differences in the ADAS-cog or the ADCS-CGIC scores in the entire group. But a preplanned subgroup analysis turned up an intriguing finding in the 78 patients who were also taking an acetylcholinesterase inhibitor (AChEI).

Although they didn’t improve cognitively, patients taking the combination of an AChEI and leuprolide held their scores at baseline level in the ADAS-cog and ADCS-CGIC throughout the 36-week follow-up period. At 48 weeks, mean ADAS-cog score declined by 3.3 in the placebo group, 4.1 in the low-dose combination group, and 0.18 in the high-dose combination group.

Results were similarly significant on the ADCS-CGIC measure, with mean declines of 63% and 82% in the placebo and low-dose groups, respectively, compared with a 38% decline in the high-dose group.

The subgroup analysis found no differences on the other measures.

Dr. Bowen said the results of his study are even more intriguing when viewed in light of a studypublished by investigators at the Dana Farber Cancer Institute that showed a 50% reduction in Alzheimer’s incidence in men who had received leuprolide for prostate cancer.

“This was remarkably similar to what we saw in our own 12-year Medicare database review,” which examined incident Alzheimer’s after prostate cancer, gallbladder surgery, hernia repair, and enlarged prostate. “Again, the decrease in the risk of developing Alzheimer’s associated with prostate cancer was about 50%.”

Dr. Bowen noted that his data are about 10 years old now. He holds a soon-to-expire patent on the use of leuprolide for Alzheimer’s and was pursuing that with a corporation. However, the company fell apart and he said he has become free to share the information only now.

But the data are enough for him to be using the treatment on at least a few patients. “I have about five or six people, both men and women, who are taking it in combination with an AChEI. The families are very happy with what they see, and I’m hoping we can get the word out so we can accumulate more data on it.”

[email protected]

On Twitter @alz_gal

PHILADELPHIA – Leuprolide acetate, in combination with an acetylcholinesterase inhibitor, helped to preserve cognitive function in Alzheimer’s disease patients in an exploratory study.

The study is small and the results are modest. But they do warrant further investigation in a larger group, Dr. Richard L. Bowen said at the Clinical Trials Conference on Alzheimer’s Disease.

Leuprolide acetate is an agonist of gonadotropin-releasing hormone (GnRH). Dr. Bowen, a family physician in Charleston, S.C., has long postulated that luteinizing hormone, which is highly present in Alzheimer’s brains – especially in the hippocampus – predisposes to cognitive decline. Some preclinical evidence exists to support the idea that luteinizing hormone may modulate amyloid precursor processing predisposing to amyloid plaque formation. Leuprolide’s effect of indirectly down-regulating the secretion of luteinizing hormone by desensitizing GnRH receptors improved cognition in a mouse model of Alzheimer’s, Dr. Bowen noted.

But it was actually a conversation about an Alzheimer’s patent with prostate cancer that sparked his 10-year work on leuprolide. “As a family practice physician, I was doing an annual exam on a postmenopausal woman, talking about the risks and benefits of hormone replacement therapy. She mentioned that her husband, who had Alzheimer’s, had been getting ‘some kind of hormone therapy’ for his prostate cancer. And she said very specifically that since he’d been on it he had not gotten any worse, and in fact, had improved a little,” he said in an interview.

This started Dr. Bowen to thinking about the relationship between gonadotropin suppression and its possible link to neurons and cognition. “Gonadotropins are very important in cell division and very high in fetal life – obviously important for fetal development, when you do want lots of cell division.”

Estrogen and testosterone eventually take center stage in human life, effectively shutting down gonadotropin production – for a while, at least. But when estrogen levels fall at menopause, gonadotropins rise again. “This could predispose terminally differentiated neurons – which aren’t supposed to divide – to cell division, thus, death.”

His theory holds that such a process could also increase amyloid burden. “This does seem to pan out in cellular and animal models, where the expression of gonadotropins in the brain perfectly correlates with amyloid deposition. It’s a coherent model of this disease that speaks to why and when we develop it.”

In 2004, Dr. Bowen and his colleagues published a paperdemonstrating that neuroblastoma cells exposed to luteinizing hormone showed a significant increase in amyloid precursor protein and a resultant increase in amyloidogenic processing.

That same paper found that leuprolide treatment in an ovariectomized Alzheimer’s mouse model decreased amyloid expression, suggesting that luteinizing hormone, not estrogen, drove the change.

At the meeting, he reported a 48-week, dose-ranging study of 109 women with mild to moderate Alzheimer’s. They received either placebo or leuprolide acetate injections with a low dose (11.25 mg) or high dose (22.5 mg), which were carried out over 12 weeks, with cognitive assessments conducted at regular intervals during the remainder of the study.

The primary endpoints were scores on the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC). Secondary endpoints included the Neuropsychiatric Inventory, Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Burden Interview, and ADCS-CGI Severity Rating.

There were no significant between-group differences in the ADAS-cog or the ADCS-CGIC scores in the entire group. But a preplanned subgroup analysis turned up an intriguing finding in the 78 patients who were also taking an acetylcholinesterase inhibitor (AChEI).

Although they didn’t improve cognitively, patients taking the combination of an AChEI and leuprolide held their scores at baseline level in the ADAS-cog and ADCS-CGIC throughout the 36-week follow-up period. At 48 weeks, mean ADAS-cog score declined by 3.3 in the placebo group, 4.1 in the low-dose combination group, and 0.18 in the high-dose combination group.

Results were similarly significant on the ADCS-CGIC measure, with mean declines of 63% and 82% in the placebo and low-dose groups, respectively, compared with a 38% decline in the high-dose group.

The subgroup analysis found no differences on the other measures.

Dr. Bowen said the results of his study are even more intriguing when viewed in light of a studypublished by investigators at the Dana Farber Cancer Institute that showed a 50% reduction in Alzheimer’s incidence in men who had received leuprolide for prostate cancer.

“This was remarkably similar to what we saw in our own 12-year Medicare database review,” which examined incident Alzheimer’s after prostate cancer, gallbladder surgery, hernia repair, and enlarged prostate. “Again, the decrease in the risk of developing Alzheimer’s associated with prostate cancer was about 50%.”

Dr. Bowen noted that his data are about 10 years old now. He holds a soon-to-expire patent on the use of leuprolide for Alzheimer’s and was pursuing that with a corporation. However, the company fell apart and he said he has become free to share the information only now.

But the data are enough for him to be using the treatment on at least a few patients. “I have about five or six people, both men and women, who are taking it in combination with an AChEI. The families are very happy with what they see, and I’m hoping we can get the word out so we can accumulate more data on it.”

[email protected]

On Twitter @alz_gal

PHILADELPHIA – An amyloid PET scan with florbetapir detected which patients with mild cognitive impairment had a high risk for further cognitive decline to Alzheimer’s disease in a large analysis of patients in the Alzheimer’s Disease Neuroimaging Initiative.

Participants who tested positive for amyloid on florbetapir (Amyvid) PET scan at baseline were five times more likely to convert to Alzheimer’s dementia within 3 years than were amyloid-negative subjects, according to data from the large, multisite imaging registry.

The finding suggests that amyloid imaging could help rule out Alzheimer’s as the underlying cause of cognitive problems, allowing physicians to focus more closely on other potential diagnoses, said Mr. Ming Lu, lead statistician at Avid Radiopharmaceuticals, a subsidiary of Eli Lilly,which markets florbetapir and sponsored the study.

“This study supports the hypothesis that amyloid PET scans are able to detect those levels of AD pathology that are associated with risk of cognitive decline, even in subjects that are not showing evidence of dementia,” Mr. Lu said in an interview at the Clinical Trials Conference on Alzheimer’s Disease, where he presented the study. “It also underscores the potential importance of diagnosing the cause of someone’s cognitive decline earlier rather than later, as this may provide useful information for physician’s management/treatment plan on these patients.”

Similar findings have been previously noted in smaller studies; this one, comprising 478 subjects, is the largest prospective study to date to look at the issue.

On PET imaging, florbetapir binds to amyloid plaques, a pathophysiologic hallmark of Alzheimer’s. So far, the agent is used only in studies of patients with diagnosed mild cognitive impairment (MCI) or Alzheimer’s disease, and patients are limited to one scan. It is not covered by Medicare in clinical use.

The patients had a mean age of 72 years, but ranged from 48 to 91 years. All had undergone at least one florbetapir scan as well as extensive cognitive testing with a variety of instruments, including the widely used Mini-Mental State Examination (MMSE), the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

On imaging, 212 were amyloid negative and 266 were amyloid positive. Over a 3-year follow-up period, amyloid-positive patients declined a mean of 4.03 points on the ADAS-cog, compared with 0.26 points for amyloid-negative patients. Amyloid-positive patients declined 2.61 points on the MMSE, compared with 0.40 in the negative patients, and on the CDR-SB, the change was 1.53 vs. –0.11 points. All of these changes were statistically significant, Mr. Lu said.

Declines of this magnitude would correlate with significant clinical changes, Mr. Lu noted. Compared with the amyloid-negative patients, the amyloid-positive patients had a twofold higher risk to progress to a clinically significant change (ADAS-cog score decline of 4 points or more), and nearly a fivefold higher risk of conversion to Alzheimer’s.

[email protected]

On Twitter @alz_gal

PHILADELPHIA – An amyloid PET scan with florbetapir detected which patients with mild cognitive impairment had a high risk for further cognitive decline to Alzheimer’s disease in a large analysis of patients in the Alzheimer’s Disease Neuroimaging Initiative.

Participants who tested positive for amyloid on florbetapir (Amyvid) PET scan at baseline were five times more likely to convert to Alzheimer’s dementia within 3 years than were amyloid-negative subjects, according to data from the large, multisite imaging registry.

The finding suggests that amyloid imaging could help rule out Alzheimer’s as the underlying cause of cognitive problems, allowing physicians to focus more closely on other potential diagnoses, said Mr. Ming Lu, lead statistician at Avid Radiopharmaceuticals, a subsidiary of Eli Lilly,which markets florbetapir and sponsored the study.

“This study supports the hypothesis that amyloid PET scans are able to detect those levels of AD pathology that are associated with risk of cognitive decline, even in subjects that are not showing evidence of dementia,” Mr. Lu said in an interview at the Clinical Trials Conference on Alzheimer’s Disease, where he presented the study. “It also underscores the potential importance of diagnosing the cause of someone’s cognitive decline earlier rather than later, as this may provide useful information for physician’s management/treatment plan on these patients.”

Similar findings have been previously noted in smaller studies; this one, comprising 478 subjects, is the largest prospective study to date to look at the issue.

On PET imaging, florbetapir binds to amyloid plaques, a pathophysiologic hallmark of Alzheimer’s. So far, the agent is used only in studies of patients with diagnosed mild cognitive impairment (MCI) or Alzheimer’s disease, and patients are limited to one scan. It is not covered by Medicare in clinical use.

The patients had a mean age of 72 years, but ranged from 48 to 91 years. All had undergone at least one florbetapir scan as well as extensive cognitive testing with a variety of instruments, including the widely used Mini-Mental State Examination (MMSE), the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

On imaging, 212 were amyloid negative and 266 were amyloid positive. Over a 3-year follow-up period, amyloid-positive patients declined a mean of 4.03 points on the ADAS-cog, compared with 0.26 points for amyloid-negative patients. Amyloid-positive patients declined 2.61 points on the MMSE, compared with 0.40 in the negative patients, and on the CDR-SB, the change was 1.53 vs. –0.11 points. All of these changes were statistically significant, Mr. Lu said.

Declines of this magnitude would correlate with significant clinical changes, Mr. Lu noted. Compared with the amyloid-negative patients, the amyloid-positive patients had a twofold higher risk to progress to a clinically significant change (ADAS-cog score decline of 4 points or more), and nearly a fivefold higher risk of conversion to Alzheimer’s.

[email protected]

On Twitter @alz_gal

PHILADELPHIA – An amyloid PET scan with florbetapir detected which patients with mild cognitive impairment had a high risk for further cognitive decline to Alzheimer’s disease in a large analysis of patients in the Alzheimer’s Disease Neuroimaging Initiative.

Participants who tested positive for amyloid on florbetapir (Amyvid) PET scan at baseline were five times more likely to convert to Alzheimer’s dementia within 3 years than were amyloid-negative subjects, according to data from the large, multisite imaging registry.

The finding suggests that amyloid imaging could help rule out Alzheimer’s as the underlying cause of cognitive problems, allowing physicians to focus more closely on other potential diagnoses, said Mr. Ming Lu, lead statistician at Avid Radiopharmaceuticals, a subsidiary of Eli Lilly,which markets florbetapir and sponsored the study.

“This study supports the hypothesis that amyloid PET scans are able to detect those levels of AD pathology that are associated with risk of cognitive decline, even in subjects that are not showing evidence of dementia,” Mr. Lu said in an interview at the Clinical Trials Conference on Alzheimer’s Disease, where he presented the study. “It also underscores the potential importance of diagnosing the cause of someone’s cognitive decline earlier rather than later, as this may provide useful information for physician’s management/treatment plan on these patients.”

Similar findings have been previously noted in smaller studies; this one, comprising 478 subjects, is the largest prospective study to date to look at the issue.

On PET imaging, florbetapir binds to amyloid plaques, a pathophysiologic hallmark of Alzheimer’s. So far, the agent is used only in studies of patients with diagnosed mild cognitive impairment (MCI) or Alzheimer’s disease, and patients are limited to one scan. It is not covered by Medicare in clinical use.

The patients had a mean age of 72 years, but ranged from 48 to 91 years. All had undergone at least one florbetapir scan as well as extensive cognitive testing with a variety of instruments, including the widely used Mini-Mental State Examination (MMSE), the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

On imaging, 212 were amyloid negative and 266 were amyloid positive. Over a 3-year follow-up period, amyloid-positive patients declined a mean of 4.03 points on the ADAS-cog, compared with 0.26 points for amyloid-negative patients. Amyloid-positive patients declined 2.61 points on the MMSE, compared with 0.40 in the negative patients, and on the CDR-SB, the change was 1.53 vs. –0.11 points. All of these changes were statistically significant, Mr. Lu said.

Declines of this magnitude would correlate with significant clinical changes, Mr. Lu noted. Compared with the amyloid-negative patients, the amyloid-positive patients had a twofold higher risk to progress to a clinically significant change (ADAS-cog score decline of 4 points or more), and nearly a fivefold higher risk of conversion to Alzheimer’s.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Male breast cancers share some important characteristics with female breast cancers: The tumors found in males are usually hormone receptor positive and of luminal A subtype, and respond less favorably if estrogen and progesterone receptor negative.

And like female breast cancers, both overall and breast cancer–specific survival rates have been increasing over the last 20 years, although not to the extent of survival improvements in women, Dr. Fatima Cardoso said at the San Antonio Breast Cancer Symposium.

Michele G. Sullivan/Frontline Medical News

Dr. Cardoso of the European School of Oncology Breast Cancer Program, Lisbon, presented the initial findings of the Male Breast Cancer International Program, a project intended to identify, characterize, and improve treatment for male breast cancers. The retrospective joint analysis is the first part of the three-step study, she said. In addition to identifying patients in the 10 countries involved (in the United States, western Europe, and Scandinavia), step one includes a collection of tumor blocks for central analysis in labs in the United States and the Netherlands.

Step two, already underway, is building a prospective international registry of all male breast cancer cases in the most recent 30 months of the study, including collection of tumor samples and blood, and a quality of life substudy.

Step three will comprise randomized treatment trials, one of which is “far along in the planning stage,” Dr. Cardoso said.

The retrospective cohort comprised 1,822 men who were diagnosed and treated for breast cancer from 1990 to 2010, with tumor assessments available for 1,483. About two-thirds of the men were older than 50 years; 25% were 75 or older. Just 2% were younger than 40 years.

Most cancers (71%) were local. Almost 60% were node negative, and 30% positive for one node. Two nodes were involved in 5% and the rest had three involved.

Breast-conserving surgery was the most common primary treatment (96%), with 4% undergoing a modified radical mastectomy. Three-fourths underwent both a sentinel node biopsy and axillary dissection; 18% had a sentinel node biopsy only, and the rest had no nodal investigation. There was a slight trend over the study period for more sentinel node biopsies alone, and less axillary dissection, but the number of men without an investigation stayed steady.

After breast-conserving surgery, all of the node-positive patients had adjuvant radiotherapy, as did 46% of the node-negative patients. Of the node-positive patients who had mastectomy, 69% received radiotherapy and 31% did not.

Adjuvant chemotherapy was administered to 70% of patients overall, with anthracyclines the most commonly used agent (43%). Others were the combination of anthracyclines and taxanes (32%); the combination of cyclophosphamide, methotrexate and fluorouracil (15%); and other unspecified regimens in the remainder.

Most men also received endocrine therapy (77%), with tamoxifen being the most common agent (88%).

Invasive ductal carcinoma was by far the most common diagnosis (about 85%). About half the tumors were grade 2; the rest were evenly split between grades 1 and 3.

The vast majority (1,053) were estrogen receptor positive with 93% having high expression. Progesterone receptor positivity occurred in 939 tumors, with 35% having high expression.

Most of the tumors were positive for androgen expression (1,027), again with high expression (88%). Two percent were human epidermal growth factor 2 (HER2) positive.

Not surprisingly, median overall survival was best in patients with nonmetastatic, nonnodal cancers (10.4 years). It was about 8.4 years for those with nonmetastatic, node-positive tumors, and 2.6 years for those with metastatic cancers.

Median overall mortality has significantly decreased over the years: About 70% of those diagnosed from 1990 to 1995 had died within 9 years, compared to about 40% of those diagnosed from 2006 to 2010. But breast cancer–specific mortality remained about the same, with less than 20% of patients dying by the end of follow-up.

Those with estrogen receptor–positive tumors did best, especially if they had high expression, while all of those with ER-negative tumors had died by 6 years after diagnosis. Findings were similar among those with androgen and progesterone receptor–negative tumors.

“Hormone receptor status had a very good prognostic value, with positive, highly expressed tumors having much better outcomes,” Dr. Cardoso said, adding that tumors in this initial phase of the study are still being examined.

She had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Male breast cancers share some important characteristics with female breast cancers: The tumors found in males are usually hormone receptor positive and of luminal A subtype, and respond less favorably if estrogen and progesterone receptor negative.

And like female breast cancers, both overall and breast cancer–specific survival rates have been increasing over the last 20 years, although not to the extent of survival improvements in women, Dr. Fatima Cardoso said at the San Antonio Breast Cancer Symposium.

Michele G. Sullivan/Frontline Medical News

Dr. Cardoso of the European School of Oncology Breast Cancer Program, Lisbon, presented the initial findings of the Male Breast Cancer International Program, a project intended to identify, characterize, and improve treatment for male breast cancers. The retrospective joint analysis is the first part of the three-step study, she said. In addition to identifying patients in the 10 countries involved (in the United States, western Europe, and Scandinavia), step one includes a collection of tumor blocks for central analysis in labs in the United States and the Netherlands.

Step two, already underway, is building a prospective international registry of all male breast cancer cases in the most recent 30 months of the study, including collection of tumor samples and blood, and a quality of life substudy.

Step three will comprise randomized treatment trials, one of which is “far along in the planning stage,” Dr. Cardoso said.

The retrospective cohort comprised 1,822 men who were diagnosed and treated for breast cancer from 1990 to 2010, with tumor assessments available for 1,483. About two-thirds of the men were older than 50 years; 25% were 75 or older. Just 2% were younger than 40 years.

Most cancers (71%) were local. Almost 60% were node negative, and 30% positive for one node. Two nodes were involved in 5% and the rest had three involved.

Breast-conserving surgery was the most common primary treatment (96%), with 4% undergoing a modified radical mastectomy. Three-fourths underwent both a sentinel node biopsy and axillary dissection; 18% had a sentinel node biopsy only, and the rest had no nodal investigation. There was a slight trend over the study period for more sentinel node biopsies alone, and less axillary dissection, but the number of men without an investigation stayed steady.

After breast-conserving surgery, all of the node-positive patients had adjuvant radiotherapy, as did 46% of the node-negative patients. Of the node-positive patients who had mastectomy, 69% received radiotherapy and 31% did not.

Adjuvant chemotherapy was administered to 70% of patients overall, with anthracyclines the most commonly used agent (43%). Others were the combination of anthracyclines and taxanes (32%); the combination of cyclophosphamide, methotrexate and fluorouracil (15%); and other unspecified regimens in the remainder.

Most men also received endocrine therapy (77%), with tamoxifen being the most common agent (88%).

Invasive ductal carcinoma was by far the most common diagnosis (about 85%). About half the tumors were grade 2; the rest were evenly split between grades 1 and 3.

The vast majority (1,053) were estrogen receptor positive with 93% having high expression. Progesterone receptor positivity occurred in 939 tumors, with 35% having high expression.

Most of the tumors were positive for androgen expression (1,027), again with high expression (88%). Two percent were human epidermal growth factor 2 (HER2) positive.

Not surprisingly, median overall survival was best in patients with nonmetastatic, nonnodal cancers (10.4 years). It was about 8.4 years for those with nonmetastatic, node-positive tumors, and 2.6 years for those with metastatic cancers.

Median overall mortality has significantly decreased over the years: About 70% of those diagnosed from 1990 to 1995 had died within 9 years, compared to about 40% of those diagnosed from 2006 to 2010. But breast cancer–specific mortality remained about the same, with less than 20% of patients dying by the end of follow-up.

Those with estrogen receptor–positive tumors did best, especially if they had high expression, while all of those with ER-negative tumors had died by 6 years after diagnosis. Findings were similar among those with androgen and progesterone receptor–negative tumors.

“Hormone receptor status had a very good prognostic value, with positive, highly expressed tumors having much better outcomes,” Dr. Cardoso said, adding that tumors in this initial phase of the study are still being examined.

She had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Male breast cancers share some important characteristics with female breast cancers: The tumors found in males are usually hormone receptor positive and of luminal A subtype, and respond less favorably if estrogen and progesterone receptor negative.

And like female breast cancers, both overall and breast cancer–specific survival rates have been increasing over the last 20 years, although not to the extent of survival improvements in women, Dr. Fatima Cardoso said at the San Antonio Breast Cancer Symposium.

Michele G. Sullivan/Frontline Medical News

Dr. Cardoso of the European School of Oncology Breast Cancer Program, Lisbon, presented the initial findings of the Male Breast Cancer International Program, a project intended to identify, characterize, and improve treatment for male breast cancers. The retrospective joint analysis is the first part of the three-step study, she said. In addition to identifying patients in the 10 countries involved (in the United States, western Europe, and Scandinavia), step one includes a collection of tumor blocks for central analysis in labs in the United States and the Netherlands.

Step two, already underway, is building a prospective international registry of all male breast cancer cases in the most recent 30 months of the study, including collection of tumor samples and blood, and a quality of life substudy.

Step three will comprise randomized treatment trials, one of which is “far along in the planning stage,” Dr. Cardoso said.

The retrospective cohort comprised 1,822 men who were diagnosed and treated for breast cancer from 1990 to 2010, with tumor assessments available for 1,483. About two-thirds of the men were older than 50 years; 25% were 75 or older. Just 2% were younger than 40 years.

Most cancers (71%) were local. Almost 60% were node negative, and 30% positive for one node. Two nodes were involved in 5% and the rest had three involved.

Breast-conserving surgery was the most common primary treatment (96%), with 4% undergoing a modified radical mastectomy. Three-fourths underwent both a sentinel node biopsy and axillary dissection; 18% had a sentinel node biopsy only, and the rest had no nodal investigation. There was a slight trend over the study period for more sentinel node biopsies alone, and less axillary dissection, but the number of men without an investigation stayed steady.

After breast-conserving surgery, all of the node-positive patients had adjuvant radiotherapy, as did 46% of the node-negative patients. Of the node-positive patients who had mastectomy, 69% received radiotherapy and 31% did not.

Adjuvant chemotherapy was administered to 70% of patients overall, with anthracyclines the most commonly used agent (43%). Others were the combination of anthracyclines and taxanes (32%); the combination of cyclophosphamide, methotrexate and fluorouracil (15%); and other unspecified regimens in the remainder.

Most men also received endocrine therapy (77%), with tamoxifen being the most common agent (88%).

Invasive ductal carcinoma was by far the most common diagnosis (about 85%). About half the tumors were grade 2; the rest were evenly split between grades 1 and 3.

The vast majority (1,053) were estrogen receptor positive with 93% having high expression. Progesterone receptor positivity occurred in 939 tumors, with 35% having high expression.

Most of the tumors were positive for androgen expression (1,027), again with high expression (88%). Two percent were human epidermal growth factor 2 (HER2) positive.

Not surprisingly, median overall survival was best in patients with nonmetastatic, nonnodal cancers (10.4 years). It was about 8.4 years for those with nonmetastatic, node-positive tumors, and 2.6 years for those with metastatic cancers.

Median overall mortality has significantly decreased over the years: About 70% of those diagnosed from 1990 to 1995 had died within 9 years, compared to about 40% of those diagnosed from 2006 to 2010. But breast cancer–specific mortality remained about the same, with less than 20% of patients dying by the end of follow-up.

Those with estrogen receptor–positive tumors did best, especially if they had high expression, while all of those with ER-negative tumors had died by 6 years after diagnosis. Findings were similar among those with androgen and progesterone receptor–negative tumors.

“Hormone receptor status had a very good prognostic value, with positive, highly expressed tumors having much better outcomes,” Dr. Cardoso said, adding that tumors in this initial phase of the study are still being examined.

She had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – An accelerated course of partial breast irradiation was as effective as whole breast irradiation for women with early breast cancer, with significantly fewer adverse events.

The technique may be a suitable alternative for select patients who wish to minimize side effects without compromising clinical outcomes, Dr. Lorenzo Livi said at the San Antonio Breast Cancer Symposium.

He reported the 5-year results of an Italian study that randomized women with early breast cancer to one of two radiation regimens: conventional (tangential field) fractionated whole breast treatment or accelerated partial breast irradiation plus intensity-modulated radiotherapy.

Michele G. Sullivan/Frontline Medical News

The patients were highly selected, with a primary tumor size of less than 25 mm and negative surgical margins of more than 5 mm, said Dr. Livi, a radiation oncologist at the University of Florence, Italy.

The cohort comprised 520 women. Most (about 85%) were node-negative; 95% of the tumors were estrogen receptor–positive, and 90% were progesterone receptor–positive. The most frequent molecular subtype was luminal A (about 75%); less than 5% were triple-negative.

The median follow-up for this portion of the study was 5 years. There were six ipsilateral breast tumor recurrences – three in each group. There were three local relapses, all in the whole breast irradiation group. The 5-year recurrence rate was 1.4% in the whole breast irradiation group and 1.5% in the partial breast irradiation group. The mean time to ipsilateral breast recurrence was 3 years, and there was no significant between-group difference in this timing.

There were 10 contralateral recurrences (seven in the whole breast group vs. three in the partial irradiation group). Distant metastases occurred in seven patients (four and three, respectively).

The 5-year overall survival rate was excellent, Dr. Livi noted: 97% in the whole breast irradiation group and 99% in the partial irradiation group.

Skin toxicity of any grade was significantly less common in the partial group (49 vs. 181). Significantly more patients in the partial irradiation group were completely free of adverse events (197 vs. 93). There were no grade 3 adverse events in either group. Two women in the whole breast irradiation group experienced a grade 2 toxicity- both of these were skin fibrosis.

Almost all patients (90%) reported good or excellent cosmetic results.

Dr. Livi fielded a few questions during the discussion period, one of which dealt with the cost of partial irradiation treatment. Since the procedure is more expensive, and the results similar, the discussant wondered whether it would be worth the additional cost. Dr Livi said the question is difficult for him to answer, because Italy’s national health care system does not charge patients for the treatment. He did say reimbursement for the treatments differs, but he did not elaborate.

He had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – An accelerated course of partial breast irradiation was as effective as whole breast irradiation for women with early breast cancer, with significantly fewer adverse events.

The technique may be a suitable alternative for select patients who wish to minimize side effects without compromising clinical outcomes, Dr. Lorenzo Livi said at the San Antonio Breast Cancer Symposium.

He reported the 5-year results of an Italian study that randomized women with early breast cancer to one of two radiation regimens: conventional (tangential field) fractionated whole breast treatment or accelerated partial breast irradiation plus intensity-modulated radiotherapy.

Michele G. Sullivan/Frontline Medical News

The patients were highly selected, with a primary tumor size of less than 25 mm and negative surgical margins of more than 5 mm, said Dr. Livi, a radiation oncologist at the University of Florence, Italy.

The cohort comprised 520 women. Most (about 85%) were node-negative; 95% of the tumors were estrogen receptor–positive, and 90% were progesterone receptor–positive. The most frequent molecular subtype was luminal A (about 75%); less than 5% were triple-negative.

The median follow-up for this portion of the study was 5 years. There were six ipsilateral breast tumor recurrences – three in each group. There were three local relapses, all in the whole breast irradiation group. The 5-year recurrence rate was 1.4% in the whole breast irradiation group and 1.5% in the partial breast irradiation group. The mean time to ipsilateral breast recurrence was 3 years, and there was no significant between-group difference in this timing.

There were 10 contralateral recurrences (seven in the whole breast group vs. three in the partial irradiation group). Distant metastases occurred in seven patients (four and three, respectively).

The 5-year overall survival rate was excellent, Dr. Livi noted: 97% in the whole breast irradiation group and 99% in the partial irradiation group.

Skin toxicity of any grade was significantly less common in the partial group (49 vs. 181). Significantly more patients in the partial irradiation group were completely free of adverse events (197 vs. 93). There were no grade 3 adverse events in either group. Two women in the whole breast irradiation group experienced a grade 2 toxicity- both of these were skin fibrosis.

Almost all patients (90%) reported good or excellent cosmetic results.

Dr. Livi fielded a few questions during the discussion period, one of which dealt with the cost of partial irradiation treatment. Since the procedure is more expensive, and the results similar, the discussant wondered whether it would be worth the additional cost. Dr Livi said the question is difficult for him to answer, because Italy’s national health care system does not charge patients for the treatment. He did say reimbursement for the treatments differs, but he did not elaborate.

He had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – An accelerated course of partial breast irradiation was as effective as whole breast irradiation for women with early breast cancer, with significantly fewer adverse events.

The technique may be a suitable alternative for select patients who wish to minimize side effects without compromising clinical outcomes, Dr. Lorenzo Livi said at the San Antonio Breast Cancer Symposium.

He reported the 5-year results of an Italian study that randomized women with early breast cancer to one of two radiation regimens: conventional (tangential field) fractionated whole breast treatment or accelerated partial breast irradiation plus intensity-modulated radiotherapy.

Michele G. Sullivan/Frontline Medical News

The patients were highly selected, with a primary tumor size of less than 25 mm and negative surgical margins of more than 5 mm, said Dr. Livi, a radiation oncologist at the University of Florence, Italy.

The cohort comprised 520 women. Most (about 85%) were node-negative; 95% of the tumors were estrogen receptor–positive, and 90% were progesterone receptor–positive. The most frequent molecular subtype was luminal A (about 75%); less than 5% were triple-negative.

The median follow-up for this portion of the study was 5 years. There were six ipsilateral breast tumor recurrences – three in each group. There were three local relapses, all in the whole breast irradiation group. The 5-year recurrence rate was 1.4% in the whole breast irradiation group and 1.5% in the partial breast irradiation group. The mean time to ipsilateral breast recurrence was 3 years, and there was no significant between-group difference in this timing.

There were 10 contralateral recurrences (seven in the whole breast group vs. three in the partial irradiation group). Distant metastases occurred in seven patients (four and three, respectively).

The 5-year overall survival rate was excellent, Dr. Livi noted: 97% in the whole breast irradiation group and 99% in the partial irradiation group.

Skin toxicity of any grade was significantly less common in the partial group (49 vs. 181). Significantly more patients in the partial irradiation group were completely free of adverse events (197 vs. 93). There were no grade 3 adverse events in either group. Two women in the whole breast irradiation group experienced a grade 2 toxicity- both of these were skin fibrosis.

Almost all patients (90%) reported good or excellent cosmetic results.

Dr. Livi fielded a few questions during the discussion period, one of which dealt with the cost of partial irradiation treatment. Since the procedure is more expensive, and the results similar, the discussant wondered whether it would be worth the additional cost. Dr Livi said the question is difficult for him to answer, because Italy’s national health care system does not charge patients for the treatment. He did say reimbursement for the treatments differs, but he did not elaborate.

He had no financial disclosures.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Losing weight and exercising may be an important key to good outcomes in some women with breast cancer – especially those with hormone receptor–negative tumors.

For women with tumors that are both estrogen and progesterone receptor negative, losing at least 5 pounds or 5% of total body weight decreased the 10-year risk of all-cause mortality by 64%, Dr. Rowan T. Chlebowski said at the San Antonio Breast Cancer Symposium.

Although it was a post hoc exploratory analysis, the subgroup findings suggest that a lifestyle intervention program could be an effective way to help increase a woman’s chances of surviving, said Dr. Chlebowski, chief of medical oncology at the UCLA Medical Center, Los Angeles.

“From a scientific standpoint, others will have to look at this post hoc analysis and decide whether the data warrant further investigation in a trial to confirm the findings,” he said. “But, on an operational basis, for a woman with breast cancer, there are so many other health benefits associated with this kind of weight loss. For example, this has been shown to significantly reduce the risk of progression from prediabetes to diabetes – and that is a very important health consideration for women with breast cancer.”

And obviously, he added, losing weight and getting active carry a myriad of other health benefits, all of which exert their own positive influences.

Dr. Chlebowski reported long-term follow-up data from the Women’s Intervention Nutrition Study (WINS). It enrolled 2,437 women from 1994 to 2001 who had been treated for early-stage breast cancer. The women, aged 48-79 years, were randomly assigned to a lower-fat dietary intervention group or to a control group that ate their regular diet. The intervention group met monthly with a registered dietitian and provided food journals. They were also encouraged to increase physical activity.

At the start of the study, both groups consumed similar amounts of calories from fat, about 57 g/day or 30% of daily caloric intake. At the end of the first year of observation, the women in the dietary intervention group had reduced their fat intake by an average of 24 g/day, compared with only a 5-gram/day drop in the control group. The difference between the two groups was maintained throughout the trial. By the fifth year of the trial, the women in the intervention group weighed an average of 6 pounds less than did the women in the control group.

But at the current follow-up (maximum of 20 years), there was no significant between-group difference in disease-free survival (17% deaths in the control groups vs. 13.6% in the intervention group), either in the entire group or in the subgroup of those with estrogen and progesterone receptor–positive tumors.

However, in the subanalysis of those who were hormone receptor negative, the difference was significant, with a 2-year survival advantage in the intervention group (14 vs. 12 years; hazard ratio, 0.64; P = .045).

The findings may be particularly important for women with triple-negative tumors, since, Dr. Chlebowski noted, data suggest that about 73% of women with ER/PR-negative cancers are anticipated to be triple negative.

He said the protective mechanism is not entirely clear, but may be due more to total calorie decrease than to decreasing fat alone – despite fat’s proclivity to increase total estrogen levels.

“Estrogen does not seem to be the driver here,” he said. Instead, the benefit may have more to do with controlling growth factors, inflammation, and glucose levels.

He did point out that the data are a bit old, and that only 6% of women in the study received tamoxifen. But he stressed that further investigation could refine the results and that, in any case, controlling weight confers a multitude of benefits.

Dr. Chlebowski had no disclosures. The WINS study was sponsored by the National Cancer Institute.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Losing weight and exercising may be an important key to good outcomes in some women with breast cancer – especially those with hormone receptor–negative tumors.

For women with tumors that are both estrogen and progesterone receptor negative, losing at least 5 pounds or 5% of total body weight decreased the 10-year risk of all-cause mortality by 64%, Dr. Rowan T. Chlebowski said at the San Antonio Breast Cancer Symposium.

Although it was a post hoc exploratory analysis, the subgroup findings suggest that a lifestyle intervention program could be an effective way to help increase a woman’s chances of surviving, said Dr. Chlebowski, chief of medical oncology at the UCLA Medical Center, Los Angeles.

“From a scientific standpoint, others will have to look at this post hoc analysis and decide whether the data warrant further investigation in a trial to confirm the findings,” he said. “But, on an operational basis, for a woman with breast cancer, there are so many other health benefits associated with this kind of weight loss. For example, this has been shown to significantly reduce the risk of progression from prediabetes to diabetes – and that is a very important health consideration for women with breast cancer.”

And obviously, he added, losing weight and getting active carry a myriad of other health benefits, all of which exert their own positive influences.

Dr. Chlebowski reported long-term follow-up data from the Women’s Intervention Nutrition Study (WINS). It enrolled 2,437 women from 1994 to 2001 who had been treated for early-stage breast cancer. The women, aged 48-79 years, were randomly assigned to a lower-fat dietary intervention group or to a control group that ate their regular diet. The intervention group met monthly with a registered dietitian and provided food journals. They were also encouraged to increase physical activity.

At the start of the study, both groups consumed similar amounts of calories from fat, about 57 g/day or 30% of daily caloric intake. At the end of the first year of observation, the women in the dietary intervention group had reduced their fat intake by an average of 24 g/day, compared with only a 5-gram/day drop in the control group. The difference between the two groups was maintained throughout the trial. By the fifth year of the trial, the women in the intervention group weighed an average of 6 pounds less than did the women in the control group.

But at the current follow-up (maximum of 20 years), there was no significant between-group difference in disease-free survival (17% deaths in the control groups vs. 13.6% in the intervention group), either in the entire group or in the subgroup of those with estrogen and progesterone receptor–positive tumors.

However, in the subanalysis of those who were hormone receptor negative, the difference was significant, with a 2-year survival advantage in the intervention group (14 vs. 12 years; hazard ratio, 0.64; P = .045).

The findings may be particularly important for women with triple-negative tumors, since, Dr. Chlebowski noted, data suggest that about 73% of women with ER/PR-negative cancers are anticipated to be triple negative.

He said the protective mechanism is not entirely clear, but may be due more to total calorie decrease than to decreasing fat alone – despite fat’s proclivity to increase total estrogen levels.

“Estrogen does not seem to be the driver here,” he said. Instead, the benefit may have more to do with controlling growth factors, inflammation, and glucose levels.

He did point out that the data are a bit old, and that only 6% of women in the study received tamoxifen. But he stressed that further investigation could refine the results and that, in any case, controlling weight confers a multitude of benefits.

Dr. Chlebowski had no disclosures. The WINS study was sponsored by the National Cancer Institute.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – Losing weight and exercising may be an important key to good outcomes in some women with breast cancer – especially those with hormone receptor–negative tumors.

For women with tumors that are both estrogen and progesterone receptor negative, losing at least 5 pounds or 5% of total body weight decreased the 10-year risk of all-cause mortality by 64%, Dr. Rowan T. Chlebowski said at the San Antonio Breast Cancer Symposium.

Although it was a post hoc exploratory analysis, the subgroup findings suggest that a lifestyle intervention program could be an effective way to help increase a woman’s chances of surviving, said Dr. Chlebowski, chief of medical oncology at the UCLA Medical Center, Los Angeles.

“From a scientific standpoint, others will have to look at this post hoc analysis and decide whether the data warrant further investigation in a trial to confirm the findings,” he said. “But, on an operational basis, for a woman with breast cancer, there are so many other health benefits associated with this kind of weight loss. For example, this has been shown to significantly reduce the risk of progression from prediabetes to diabetes – and that is a very important health consideration for women with breast cancer.”

And obviously, he added, losing weight and getting active carry a myriad of other health benefits, all of which exert their own positive influences.

Dr. Chlebowski reported long-term follow-up data from the Women’s Intervention Nutrition Study (WINS). It enrolled 2,437 women from 1994 to 2001 who had been treated for early-stage breast cancer. The women, aged 48-79 years, were randomly assigned to a lower-fat dietary intervention group or to a control group that ate their regular diet. The intervention group met monthly with a registered dietitian and provided food journals. They were also encouraged to increase physical activity.

At the start of the study, both groups consumed similar amounts of calories from fat, about 57 g/day or 30% of daily caloric intake. At the end of the first year of observation, the women in the dietary intervention group had reduced their fat intake by an average of 24 g/day, compared with only a 5-gram/day drop in the control group. The difference between the two groups was maintained throughout the trial. By the fifth year of the trial, the women in the intervention group weighed an average of 6 pounds less than did the women in the control group.

But at the current follow-up (maximum of 20 years), there was no significant between-group difference in disease-free survival (17% deaths in the control groups vs. 13.6% in the intervention group), either in the entire group or in the subgroup of those with estrogen and progesterone receptor–positive tumors.

However, in the subanalysis of those who were hormone receptor negative, the difference was significant, with a 2-year survival advantage in the intervention group (14 vs. 12 years; hazard ratio, 0.64; P = .045).

The findings may be particularly important for women with triple-negative tumors, since, Dr. Chlebowski noted, data suggest that about 73% of women with ER/PR-negative cancers are anticipated to be triple negative.

He said the protective mechanism is not entirely clear, but may be due more to total calorie decrease than to decreasing fat alone – despite fat’s proclivity to increase total estrogen levels.

“Estrogen does not seem to be the driver here,” he said. Instead, the benefit may have more to do with controlling growth factors, inflammation, and glucose levels.

He did point out that the data are a bit old, and that only 6% of women in the study received tamoxifen. But he stressed that further investigation could refine the results and that, in any case, controlling weight confers a multitude of benefits.

Dr. Chlebowski had no disclosures. The WINS study was sponsored by the National Cancer Institute.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

[email protected]

On Twitter @alz_gal

SAN ANTONIO – A genetic assay specific for ductal cancer in situ accurately predicted 10-year recurrence risk in women who underwent breast-conserving surgery as treatment for the disease.

Women whom the test identified as having a high recurrence risk were 68% more likely to have an ipsilateral recurrence of either ductal cancer in situ (DCIS) or invasive breast cancer, Dr. Eileen Rakovitch said at the San Antonio Breast Cancer Symposium. These results suggest that the Oncotype DX DCIS Score could be used as a risk stratification biomarker, said Dr. Rakovitch, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.

“We hope this will enable both clinicians and patients to understand their individual risk of progression, and to weigh the risks and benefits of available treatment. This might reduce the problems of overtreating women at low risk and undertreating women at high risk of recurrence.”

The Oncotype DX DCIS is a multigene expression assay that identifies 12 of the 21 genes included in the Oncotype DX Recurrence Score; seven of these are cancer specific and five are reference genes. It stratifies women into three 10-year risk groups according to increasing score (1-100): low-risk (less than 39), intermediate risk (39-54), and high-risk (55 and higher).

It was previously validated in a retrospective analysis of 327 selected cases, all of which were estrogen receptor–positive. In that study, all women had DCIS treatment by breast-conserving surgery alone. Tumors had to be 2.5 cm or less with nuclear grades 1 or 2; or at least 1 cm with a nuclear grade 3. Negative surgical margins of at least 3 cm were also required. In that population, after adjustment for tamoxifen use, the intermediate- and high-risk groups faced more than a doubling of the 10-year ipsilateral local recurrence risk (HR 2.31) compared to the low-risk group.

The study Dr. Rakovitch reported investigated the score’s validity in a cohort with mixed hormone receptor status, and in the subgroup of women with only ER-positive tumors.

The cohort was drawn from several Canadian health care databases that linked diagnosis, treatment, and outcome. Cases were verified by chart reviews of each stage of care. The women were treated from 1994 to 2003 and followed for a mean of 10 years. The final diagnosis was DCIS, and they were treated only with breast-conserving surgery.

Most (81%) were at least 50 years old. About half had an intermediate nuclear grade; it was low in 10% and high in the remainder. Necrosis was present in 61% of the tumors; 63% were solid and 20%, multifocal. Tumor size data were missing in about half; of those with data, 25% were 10 mm or smaller and the remainder larger than 10 mm.

Over the follow-up period, there were 100 recurrences (44 DCIS and 56 invasive cancers). The overall 10-year recurrence risk was 10%. The groups diverged significantly in risk. It was 28% in the high-risk and 33% in the intermediate-risk groups – not significantly different. But both those were significantly higher than the 13% risk in the low-risk group. These results were remarkably similar to those of the earlier validity study in women with ER-positive tumors.

Risk was further stratified by whether the recurrence was local or invasive and the results were similarly significantly different. For invasive local recurrence, the risks were 15.5%, 21%, and 8% for the high-, intermediate-, and low-risk groups. For local recurrence, the risks were 13.7%, 14% and 5.4%, respectively.

A multivariate analysis controlled for age at diagnosis, tumor subtype, and multifocality – none of these were significantly related to the risk of recurrence.

Funding for the study was provided by grants from the Canadian Cancer Society Research Institute and a research grant from Genomic Health, which makes the test. Dr. Rakovitch had no conflicts of interest.

[email protected]

On Twitter @alz_gal