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‘Robust evidence’ that exercise cuts Parkinson’s risk in women
Investigators found that among almost 99,000 women participating in the ongoing E3N study, those who exercised the most frequently had up to a 25% lower risk for PD than their less-active counterparts.
The results highlight the importance of exercising early in mid-life to prevent PD later on, study investigator Alexis Elbaz, MD, PhD, research director, French Institute of Health and Medical Research (Inserm), Paris, said in an interview.
This is especially critical since there is no cure nor disease-modifying treatments. The medications that are available are aimed at symptom reduction.
“Finding ways to prevent or delay the onset of Parkinson’s is really important, and physical activity seems to be one of the possible strategies to reduce the risk,” Dr. Elbaz said.
The study was published online in Neurology.
Direct protective effect?
Results from previous research examining the relationship physical activity and PD has been inconsistent. One meta-analysis showed a statistically significant association among men but a nonsignificant link in women.
The investigators noted that some of the findings from previous studies may have been affected by reverse causation. As nonmotor symptoms such as constipation and subtle motor signs such as tremor and balance issues can present years before a PD diagnosis, patients may reduce their physical activity because of such symptoms.
To address this potential confounder, the researchers used “lag” analyses, where data on physical activity levels in the years close to a PD diagnosis are omitted.
The study relied on data from the E3N, an ongoing cohort study of 98,995 women, born between 1925 and 1950 and recruited in 1990, who were affiliated with a French national health insurance plan that primarily covers teachers. Participants completed a questionnaire on lifestyle and medical history at baseline and follow-up questionnaires every 2-3 years.
In six of the questionnaires, participants provided details about various recreational, sports, and household activities – for example, walking, climbing stairs, gardening, and cleaning. The authors attributed metabolic equivalent of task (MET) values to each activity and multiplied METs by their frequency and duration to obtain a physical activity score.
Definite and probable PD cases were determined through self-reported physician diagnoses, anti-parkinsonian drug claims, and medical records, with diagnoses verified by an expert panel.
Researchers investigated the relationship between physical activity and PD onset in a nested-case control study that included 25,075 women (1,196 PD cases and 23,879 controls) with a mean age of 71.9 years. They found physical activity was significantly lower in cases than in controls throughout follow-up.
The difference between cases and controls began to increase at 10 years before diagnosis (P-interaction = .003). “When we looked at the trajectories of physical activity in PD patients and in controls, we saw that in the 10 years before the diagnosis, physical activity declined at a steeper rate in controls. We think this is because those subtle prodromal symptoms cause people to exercise less,” said Dr. Elbaz.
In the main analysis, which had a 10-year lag, 1,074 women developed incident PD during a mean follow-up of 17.2 years. Those in the highest quartile of physical activity had a 25% lower risk for PD vs. those in the lowest quartile (adjusted hazard ratio [HR], 0.75, 95% confidence interval [CI], 0.63-0.89).
The risk for PD decreased with increasing levels of physical activity in a linear fashion, noted Dr. Elbaz. “So doing even a little bit of physical activity is better than doing nothing at all.”
Analyses that included 15-year and 20-year lag times had similar findings.
Sensitivity analyses that adjusted for the Mediterranean diet and caffeine and dairy intake also yielded comparable results. This was also true for analyses that adjusted for comorbidities such as body mass index, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease, all of which can affect PD risk.
“This gives weight to the idea that diabetes or cardiovascular diseases do not explain the relationship between physical activity and PD, which means the most likely hypothesis is that physical activity has a direct protective effect on the brain,” said Dr. Elbaz.
Studies have shown that physical activity affects brain plasticity and can reduce oxidative stress in the brain – a key mechanism involved in PD, he added.
Physical activity is a low-risk, inexpensive, and accessible intervention. But the study was not designed to determine the types of physical activity that are most protective against PD.
The study’s main limitation is that it used self-reported physical activity rather than objective measures such as accelerometers. In addition, the participants were not necessarily representative of the general population.
Robust evidence
In an accompanying editorial, Lana M. Chahine, MD, associate professor in the department of neurology at the University of Pittsburgh, and Sirwan K. L. Darweesh, MD, PhD, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson and Movement Disorders, Nijmegen, the Netherlands, said the study “provides robust evidence” that physical activity reduces risk for PD in women.
“These results show that the field is moving in the right direction and provide a clear rationale for exercise trials to prevent or delay the onset of manifest PD in at-risk individuals” they wrote.
The study highlights “gaps” in knowledge that merit closer attention and that “further insight is warranted on how much the effects on PD vary by type, intensity, frequency, and duration of physical activity,” the editorialists noted.
Another gap is how the accuracy of assessment of physical activity can be improved beyond self-report. “Wearable sensor technology now offers the potential to assess physical activity remotely and objectively in prevention trials,” they added.
Other areas that need exploring relate to mechanisms by which physical activity reduces PD risk, and to what extent effects of physical activity vary between individuals, Dr. Chahine and Dr. Darweesh noted.
Commenting for this article, Michael S. Okun, MD, executive director of the Fixel Institute for Neurological Diseases at University of Florida Health, and medical adviser for the Parkinson’s Foundation, said the findings are “significant and important.”
Based on only a handful of previous studies, it was assumed that physical activity was associated with reduced Parkinson’s diagnosis only in men, said Dr. Okun. “The current dataset was larger and included longer-term outcomes, and it informs the field that exercise may be important for reducing the risk of Parkinson’s disease in men as well as in women.”
The investigators, the editorialists, and Dr. Okun reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Investigators found that among almost 99,000 women participating in the ongoing E3N study, those who exercised the most frequently had up to a 25% lower risk for PD than their less-active counterparts.
The results highlight the importance of exercising early in mid-life to prevent PD later on, study investigator Alexis Elbaz, MD, PhD, research director, French Institute of Health and Medical Research (Inserm), Paris, said in an interview.
This is especially critical since there is no cure nor disease-modifying treatments. The medications that are available are aimed at symptom reduction.
“Finding ways to prevent or delay the onset of Parkinson’s is really important, and physical activity seems to be one of the possible strategies to reduce the risk,” Dr. Elbaz said.
The study was published online in Neurology.
Direct protective effect?
Results from previous research examining the relationship physical activity and PD has been inconsistent. One meta-analysis showed a statistically significant association among men but a nonsignificant link in women.
The investigators noted that some of the findings from previous studies may have been affected by reverse causation. As nonmotor symptoms such as constipation and subtle motor signs such as tremor and balance issues can present years before a PD diagnosis, patients may reduce their physical activity because of such symptoms.
To address this potential confounder, the researchers used “lag” analyses, where data on physical activity levels in the years close to a PD diagnosis are omitted.
The study relied on data from the E3N, an ongoing cohort study of 98,995 women, born between 1925 and 1950 and recruited in 1990, who were affiliated with a French national health insurance plan that primarily covers teachers. Participants completed a questionnaire on lifestyle and medical history at baseline and follow-up questionnaires every 2-3 years.
In six of the questionnaires, participants provided details about various recreational, sports, and household activities – for example, walking, climbing stairs, gardening, and cleaning. The authors attributed metabolic equivalent of task (MET) values to each activity and multiplied METs by their frequency and duration to obtain a physical activity score.
Definite and probable PD cases were determined through self-reported physician diagnoses, anti-parkinsonian drug claims, and medical records, with diagnoses verified by an expert panel.
Researchers investigated the relationship between physical activity and PD onset in a nested-case control study that included 25,075 women (1,196 PD cases and 23,879 controls) with a mean age of 71.9 years. They found physical activity was significantly lower in cases than in controls throughout follow-up.
The difference between cases and controls began to increase at 10 years before diagnosis (P-interaction = .003). “When we looked at the trajectories of physical activity in PD patients and in controls, we saw that in the 10 years before the diagnosis, physical activity declined at a steeper rate in controls. We think this is because those subtle prodromal symptoms cause people to exercise less,” said Dr. Elbaz.
In the main analysis, which had a 10-year lag, 1,074 women developed incident PD during a mean follow-up of 17.2 years. Those in the highest quartile of physical activity had a 25% lower risk for PD vs. those in the lowest quartile (adjusted hazard ratio [HR], 0.75, 95% confidence interval [CI], 0.63-0.89).
The risk for PD decreased with increasing levels of physical activity in a linear fashion, noted Dr. Elbaz. “So doing even a little bit of physical activity is better than doing nothing at all.”
Analyses that included 15-year and 20-year lag times had similar findings.
Sensitivity analyses that adjusted for the Mediterranean diet and caffeine and dairy intake also yielded comparable results. This was also true for analyses that adjusted for comorbidities such as body mass index, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease, all of which can affect PD risk.
“This gives weight to the idea that diabetes or cardiovascular diseases do not explain the relationship between physical activity and PD, which means the most likely hypothesis is that physical activity has a direct protective effect on the brain,” said Dr. Elbaz.
Studies have shown that physical activity affects brain plasticity and can reduce oxidative stress in the brain – a key mechanism involved in PD, he added.
Physical activity is a low-risk, inexpensive, and accessible intervention. But the study was not designed to determine the types of physical activity that are most protective against PD.
The study’s main limitation is that it used self-reported physical activity rather than objective measures such as accelerometers. In addition, the participants were not necessarily representative of the general population.
Robust evidence
In an accompanying editorial, Lana M. Chahine, MD, associate professor in the department of neurology at the University of Pittsburgh, and Sirwan K. L. Darweesh, MD, PhD, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson and Movement Disorders, Nijmegen, the Netherlands, said the study “provides robust evidence” that physical activity reduces risk for PD in women.
“These results show that the field is moving in the right direction and provide a clear rationale for exercise trials to prevent or delay the onset of manifest PD in at-risk individuals” they wrote.
The study highlights “gaps” in knowledge that merit closer attention and that “further insight is warranted on how much the effects on PD vary by type, intensity, frequency, and duration of physical activity,” the editorialists noted.
Another gap is how the accuracy of assessment of physical activity can be improved beyond self-report. “Wearable sensor technology now offers the potential to assess physical activity remotely and objectively in prevention trials,” they added.
Other areas that need exploring relate to mechanisms by which physical activity reduces PD risk, and to what extent effects of physical activity vary between individuals, Dr. Chahine and Dr. Darweesh noted.
Commenting for this article, Michael S. Okun, MD, executive director of the Fixel Institute for Neurological Diseases at University of Florida Health, and medical adviser for the Parkinson’s Foundation, said the findings are “significant and important.”
Based on only a handful of previous studies, it was assumed that physical activity was associated with reduced Parkinson’s diagnosis only in men, said Dr. Okun. “The current dataset was larger and included longer-term outcomes, and it informs the field that exercise may be important for reducing the risk of Parkinson’s disease in men as well as in women.”
The investigators, the editorialists, and Dr. Okun reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Investigators found that among almost 99,000 women participating in the ongoing E3N study, those who exercised the most frequently had up to a 25% lower risk for PD than their less-active counterparts.
The results highlight the importance of exercising early in mid-life to prevent PD later on, study investigator Alexis Elbaz, MD, PhD, research director, French Institute of Health and Medical Research (Inserm), Paris, said in an interview.
This is especially critical since there is no cure nor disease-modifying treatments. The medications that are available are aimed at symptom reduction.
“Finding ways to prevent or delay the onset of Parkinson’s is really important, and physical activity seems to be one of the possible strategies to reduce the risk,” Dr. Elbaz said.
The study was published online in Neurology.
Direct protective effect?
Results from previous research examining the relationship physical activity and PD has been inconsistent. One meta-analysis showed a statistically significant association among men but a nonsignificant link in women.
The investigators noted that some of the findings from previous studies may have been affected by reverse causation. As nonmotor symptoms such as constipation and subtle motor signs such as tremor and balance issues can present years before a PD diagnosis, patients may reduce their physical activity because of such symptoms.
To address this potential confounder, the researchers used “lag” analyses, where data on physical activity levels in the years close to a PD diagnosis are omitted.
The study relied on data from the E3N, an ongoing cohort study of 98,995 women, born between 1925 and 1950 and recruited in 1990, who were affiliated with a French national health insurance plan that primarily covers teachers. Participants completed a questionnaire on lifestyle and medical history at baseline and follow-up questionnaires every 2-3 years.
In six of the questionnaires, participants provided details about various recreational, sports, and household activities – for example, walking, climbing stairs, gardening, and cleaning. The authors attributed metabolic equivalent of task (MET) values to each activity and multiplied METs by their frequency and duration to obtain a physical activity score.
Definite and probable PD cases were determined through self-reported physician diagnoses, anti-parkinsonian drug claims, and medical records, with diagnoses verified by an expert panel.
Researchers investigated the relationship between physical activity and PD onset in a nested-case control study that included 25,075 women (1,196 PD cases and 23,879 controls) with a mean age of 71.9 years. They found physical activity was significantly lower in cases than in controls throughout follow-up.
The difference between cases and controls began to increase at 10 years before diagnosis (P-interaction = .003). “When we looked at the trajectories of physical activity in PD patients and in controls, we saw that in the 10 years before the diagnosis, physical activity declined at a steeper rate in controls. We think this is because those subtle prodromal symptoms cause people to exercise less,” said Dr. Elbaz.
In the main analysis, which had a 10-year lag, 1,074 women developed incident PD during a mean follow-up of 17.2 years. Those in the highest quartile of physical activity had a 25% lower risk for PD vs. those in the lowest quartile (adjusted hazard ratio [HR], 0.75, 95% confidence interval [CI], 0.63-0.89).
The risk for PD decreased with increasing levels of physical activity in a linear fashion, noted Dr. Elbaz. “So doing even a little bit of physical activity is better than doing nothing at all.”
Analyses that included 15-year and 20-year lag times had similar findings.
Sensitivity analyses that adjusted for the Mediterranean diet and caffeine and dairy intake also yielded comparable results. This was also true for analyses that adjusted for comorbidities such as body mass index, hypertension, hypercholesterolemia, diabetes, and cardiovascular disease, all of which can affect PD risk.
“This gives weight to the idea that diabetes or cardiovascular diseases do not explain the relationship between physical activity and PD, which means the most likely hypothesis is that physical activity has a direct protective effect on the brain,” said Dr. Elbaz.
Studies have shown that physical activity affects brain plasticity and can reduce oxidative stress in the brain – a key mechanism involved in PD, he added.
Physical activity is a low-risk, inexpensive, and accessible intervention. But the study was not designed to determine the types of physical activity that are most protective against PD.
The study’s main limitation is that it used self-reported physical activity rather than objective measures such as accelerometers. In addition, the participants were not necessarily representative of the general population.
Robust evidence
In an accompanying editorial, Lana M. Chahine, MD, associate professor in the department of neurology at the University of Pittsburgh, and Sirwan K. L. Darweesh, MD, PhD, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Center of Expertise for Parkinson and Movement Disorders, Nijmegen, the Netherlands, said the study “provides robust evidence” that physical activity reduces risk for PD in women.
“These results show that the field is moving in the right direction and provide a clear rationale for exercise trials to prevent or delay the onset of manifest PD in at-risk individuals” they wrote.
The study highlights “gaps” in knowledge that merit closer attention and that “further insight is warranted on how much the effects on PD vary by type, intensity, frequency, and duration of physical activity,” the editorialists noted.
Another gap is how the accuracy of assessment of physical activity can be improved beyond self-report. “Wearable sensor technology now offers the potential to assess physical activity remotely and objectively in prevention trials,” they added.
Other areas that need exploring relate to mechanisms by which physical activity reduces PD risk, and to what extent effects of physical activity vary between individuals, Dr. Chahine and Dr. Darweesh noted.
Commenting for this article, Michael S. Okun, MD, executive director of the Fixel Institute for Neurological Diseases at University of Florida Health, and medical adviser for the Parkinson’s Foundation, said the findings are “significant and important.”
Based on only a handful of previous studies, it was assumed that physical activity was associated with reduced Parkinson’s diagnosis only in men, said Dr. Okun. “The current dataset was larger and included longer-term outcomes, and it informs the field that exercise may be important for reducing the risk of Parkinson’s disease in men as well as in women.”
The investigators, the editorialists, and Dr. Okun reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NEUROLOGY
Breast cancer survivors need a comprehensive care plan, says doctor
said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.
Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.
Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.
In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.
In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.
Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.
Shift to primary care
As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.
A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
Delivering the three P’s
The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .
The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.
The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.
The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.
Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.
To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.
For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.
Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.
However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.
During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
Engaging a patient’s partner early can be helpful
If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.
“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”
“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.
Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.
said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.
Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.
Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.
In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.
In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.
Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.
Shift to primary care
As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.
A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
Delivering the three P’s
The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .
The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.
The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.
The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.
Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.
To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.
For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.
Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.
However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.
During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
Engaging a patient’s partner early can be helpful
If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.
“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”
“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.
Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.
said Patricia A. Ganz, MD, during a presentation at the European Society for Medical Oncology Breast Cancer annual congress.
Several studies suggest that many breast cancer patients are not well prepared to move forward after a breast cancer diagnosis and subsequent treatments, continued Dr. Ganz, who works at the UCLA Jonsson Comprehensive Cancer Center, Los Angeles.
Meeting the survivorship needs of breast cancer patients requires addressing both their physical and psychosocial needs, Dr. Ganz said. She explained how to achieve that, but first pointed to research elaborating on what's missing from some breast cancer survivors' care and barriers to these patients having their variety of health-related needs met.
In a 2021 study published in the Journal of Cancer Survivorship, Dr. Ganz and colleagues conducted a survey of approximately 200 medical oncologists in the United States. They determined that less than 50% provide survivorship care plans to patients at the end of treatment or communicate with patients’ other physicians about follow-up care.
In a secondary analysis of data from the same survey published in 2022 in Breast Cancer Research and Treatment, Dr. Ganz and colleagues examined medical oncologists’ perceived barriers to addressing both physical and psychosocial long-term effects in breast cancer survivors. For both, lack of time was the greatest perceived barrier, cited by nearly two-thirds of oncologists. Other barriers to addressing physical effects included lack of evidence-based, effective interventions, lack of clinical algorithms to guide care, and ambiguity regarding professional responsibility at the end of treatment. Other top barriers to addressing psychosocial issues included lack of mental health providers, lack of psychosocial resources, and lack of clinician knowledge and skills.
Data from additional studies suggest that, overall, cancer patients with greater physical burdens, such as more complex and lengthy treatment regimens, also have greater psychosocial needs, Dr. Ganz noted. Plus, approximately 15%-20% of cancer survivors have ongoing anxiety and depressive symptoms.
Shift to primary care
As more breast cancer and other cancer patients survive for longer periods, more care will likely occur in general medical settings, Dr. Ganz said. Issues to be addressed will include the potential increased risk of comorbid conditions for these survivors, and whether survivorship interventions earlier in the disease trajectory will impact survivorship. For cancer patients who achieve remission after treatment, the first 5 years after a diagnosis involves treatment and short-term surveillance for late effects. Beyond 5 years, care for cancer survivors mainly involves primary care and management of any comorbid conditions, as well as surveillance for late effects and recurrences, and awareness of new research.
A patient consultation early in the process after diagnosis is the start of a continuum of care, Dr. Ganz said. A patient consultation should address symptoms related to initial treatments, such as neuropathy, pain, fatigue, and insomnia, as well as the psychological symptoms of anxiety and depression. An early consultation also should evaluate adherence to endocrine therapy and management of symptoms, if needed, with the larger goal of preparing patients for recovery and the transition to survivorship, and what to expect for long-term follow-up.
Delivering the three P’s
The “Three P’s” of survivor care for breast cancer patients are palliation, prevention, and promotion of health, according to Dr. Ganz .
The first “P,” for palliative, is a key part of survivorship care, said Dr. Ganz. Palliative care is defined as care that focuses on reducing symptom severity and improving quality of life. The biological effects of cancer treatment can be associated with physical effects, such as functional limitations and frailty, and behavioral/cognitive effects such as depression, fatigue, and cognitive deficits, she said. To manage these effects and provide palliative care, consultation is needed with specialists in relevant areas including mental health, pain management, physical medicine/rehabilitation, endocrinology, cardiology, and neurology.
The second “P,” which is for prevention in survivorship care, refers to ongoing follow-up screening to identify any potentially serious late-onset complications such as osteoporosis or cardiac disease so they can be addressed, said Dr. Ganz. Other considerations include chemoprevention if available and genetic counseling for patients with hereditary cancers. Prevention also includes counseling patients about lifestyle modifications to help prevent additional cancer.
The goal of the third “P,” which is for health promotion, is to promote risk reduction for the health problems associated with accelerated aging that may arise in cancer survivors, said Dr. Ganz.
Health promotion strategies include maintaining a healthy weight, increasing physical activity, and avoiding harmful exposures, she said. Healthy lifestyle interventions can also reduce the risk of other chronic diseases such as diabetes and heart disease.
To that end, Dr. Ganz outlined several behavioral interventions that may mitigate the effects of cancer treatment on the accelerated aging process, including stress reduction in the form of meditation or yoga, cognitive behavioral therapy, improving sleep, increasing physical activity, reducing obesity, and decreasing tobacco and alcohol use. These interventions may help reduce inflammation and promote tissue repair and healing.
For cancer survivors, the life span may be longer than the health span, and these patients may benefit from an integrated model of care, with systematic screening and consolidated appointments, rather than a fragmented model in which departments and referrals are siloed, which may result in conflicting advice or redundancy, said Dr. Ganz.
Looking ahead, more research is needed to explore models of care delivery, as requirements for survivor care will vary among patients and care settings, Dr. Ganz said.
However, regardless of setting, treatment plans and shared decision-making can help reduce potential long-term or late-emerging effects, she said. Developing a survivorship care plan can help patients learn how to enhance their recovery.
During a question and answer session, Dr. Ganz was asked about whether hormone therapy could be used for patients with hormone negative breast cancer. “I think vaginal estrogen can be used if someone is on tamoxifen,” she said. However, “we need to be cautious” in case there are remaining estrogen positive cells, in order to avoid potential metastases, and use of hormone therapy in breast cancer survivors is an individualized decision based in part on quality of life.
Engaging a patient’s partner early can be helpful
If possible, engage the patient’s partner in survivorship discussions, said Luzia Travado, PhD, head of psycho-oncology at the Champalimaud Foundation, Lisbon, who presented on the topic of sexuality and commented on survivorship during the discussion. For those women with partners, engaging the partner early in treatment often means they are more likely to play a larger role in the post treatment and long term by providing stability and emotional support.
“Make sure partners are engaged and understand that they have a role, and that this role is valued,” she said. Unfortunately, there are a lot of divorced women with breast cancer, as the disease can take a toll on relationships. However, remember “sexuality is not just sex; it is caring, loving, and intimacy.”
“To end on a positive note, it is important to empower patients, and to give them self-management skills so they can make things even better in their survivorship,” said Dr. Ganz. In spite of discussing difficulties and challenges, one of the goals of the session was to offer potential solutions and answers.
Dr. Ganz disclosed serving as editor of the cancer survivorship section on Up-to-Date, and serving as a consultant for Blue Note Therapeutics, GRAIL, InformedDNA, and Roche-Genentech. Dr. Travado had no relevant financial conflicts to disclose.
FROM ESMO BREAST CANCER 2023
Mailed HPV test kits boost cervical cancer screening
The self-sampling kits, which detect human papillomavirus (HPV), are available only for use in clinical trials, but the researchers hope that eventually these kits will be approved for use by the general public.
The researchers, from the University of North Carolina, explored use of these kits in the My Body, My Test-3 study, which was published online in The Lancet Public Health.
In a commentary published with the study, Runzhi Wang, MD, and Jennell Coleman, MD, MPH, both of Johns Hopkins University, Baltimore, said it “provides the required evidence that ... self-collected samples can be an effective strategy for hard-to-reach populations.”
The study involved 665 women (aged 25-64) in North Carolina who were either uninsured or enrolled in Medicaid or Medicare. The patients had low-income backgrounds and lived in urban areas. More than half self-reported as Black or Hispanic (55%), uninsured (78%) or unemployed (57%). None had a Pap smear in at least 4 years or a high-risk HPV test in the last 6 years.
Two-thirds of the women were mailed an HPV self-collection kit and received assistance with scheduling an in-person screening appointment. The kit included a Viba-Brush device, which is inserted into the vagina like a tampon to collect the sample.
The other third of women, the control group, only received scheduling assistance.
The team found that mailing the self-collection tests along with helping women book in-clinic appointments improved screening rates twofold, compared with just assisting patients to schedule an appointment.
Screening success among those who received the at-home collection kit was 72%, compared with 37% in the control group.
Of those who received the kits, 78% returned them. This is “impressive,” said Dr. Wang and Dr. Coleman, as previous studies have reported return rates of only 8%-20%.
About 23% of eligible women are overdue for cervical cancer screening by at least a year, according to the National Cancer Institute. Jennifer Smith, PhD, MPH, professor of epidemiology at the University of North Carolina at Chapel Hill and an author of the study, believes every woman deserves equal access to cervical screening.
“I think we really need to make efforts to increase cervical cancer screening among women who are overdue for screening by a year or more from the recommended guidelines,” Dr. Smith said. “We’ve proven along with the wide evidence both in the U.S. and globally that self-collection intervention works well and can motivate screening uptake by breaking down barriers for populations that have less access to care.”
“We’re hoping this research in combination with all of the extensive evidence on the positive performance of HPV self-collection will provide additional information to be considered by the FDA for approval of the kits for primary screening,” Dr. Smith said. 
“Government approval of at-home HPV tests would have a huge impact,” said coauthor Noel Brewer, PhD, also of UNC Chapel Hill. “We could better reach those in rural areas where cervical cancer screening is hard to come by.”
Dr. Smith has received research grants, supply donations, and consultancies for Hologic and BD Diagnostics. Dr. Brewer, Dr. Wang, and Dr. Coleman reported no conflicts of interest.
A version of this article first appeared on WebMD.com.
The self-sampling kits, which detect human papillomavirus (HPV), are available only for use in clinical trials, but the researchers hope that eventually these kits will be approved for use by the general public.
The researchers, from the University of North Carolina, explored use of these kits in the My Body, My Test-3 study, which was published online in The Lancet Public Health.
In a commentary published with the study, Runzhi Wang, MD, and Jennell Coleman, MD, MPH, both of Johns Hopkins University, Baltimore, said it “provides the required evidence that ... self-collected samples can be an effective strategy for hard-to-reach populations.”
The study involved 665 women (aged 25-64) in North Carolina who were either uninsured or enrolled in Medicaid or Medicare. The patients had low-income backgrounds and lived in urban areas. More than half self-reported as Black or Hispanic (55%), uninsured (78%) or unemployed (57%). None had a Pap smear in at least 4 years or a high-risk HPV test in the last 6 years.
Two-thirds of the women were mailed an HPV self-collection kit and received assistance with scheduling an in-person screening appointment. The kit included a Viba-Brush device, which is inserted into the vagina like a tampon to collect the sample.
The other third of women, the control group, only received scheduling assistance.
The team found that mailing the self-collection tests along with helping women book in-clinic appointments improved screening rates twofold, compared with just assisting patients to schedule an appointment.
Screening success among those who received the at-home collection kit was 72%, compared with 37% in the control group.
Of those who received the kits, 78% returned them. This is “impressive,” said Dr. Wang and Dr. Coleman, as previous studies have reported return rates of only 8%-20%.
About 23% of eligible women are overdue for cervical cancer screening by at least a year, according to the National Cancer Institute. Jennifer Smith, PhD, MPH, professor of epidemiology at the University of North Carolina at Chapel Hill and an author of the study, believes every woman deserves equal access to cervical screening.
“I think we really need to make efforts to increase cervical cancer screening among women who are overdue for screening by a year or more from the recommended guidelines,” Dr. Smith said. “We’ve proven along with the wide evidence both in the U.S. and globally that self-collection intervention works well and can motivate screening uptake by breaking down barriers for populations that have less access to care.”
“We’re hoping this research in combination with all of the extensive evidence on the positive performance of HPV self-collection will provide additional information to be considered by the FDA for approval of the kits for primary screening,” Dr. Smith said.
“Government approval of at-home HPV tests would have a huge impact,” said coauthor Noel Brewer, PhD, also of UNC Chapel Hill. “We could better reach those in rural areas where cervical cancer screening is hard to come by.”
Dr. Smith has received research grants, supply donations, and consultancies for Hologic and BD Diagnostics. Dr. Brewer, Dr. Wang, and Dr. Coleman reported no conflicts of interest.
A version of this article first appeared on WebMD.com.
The self-sampling kits, which detect human papillomavirus (HPV), are available only for use in clinical trials, but the researchers hope that eventually these kits will be approved for use by the general public.
The researchers, from the University of North Carolina, explored use of these kits in the My Body, My Test-3 study, which was published online in The Lancet Public Health.
In a commentary published with the study, Runzhi Wang, MD, and Jennell Coleman, MD, MPH, both of Johns Hopkins University, Baltimore, said it “provides the required evidence that ... self-collected samples can be an effective strategy for hard-to-reach populations.”
The study involved 665 women (aged 25-64) in North Carolina who were either uninsured or enrolled in Medicaid or Medicare. The patients had low-income backgrounds and lived in urban areas. More than half self-reported as Black or Hispanic (55%), uninsured (78%) or unemployed (57%). None had a Pap smear in at least 4 years or a high-risk HPV test in the last 6 years.
Two-thirds of the women were mailed an HPV self-collection kit and received assistance with scheduling an in-person screening appointment. The kit included a Viba-Brush device, which is inserted into the vagina like a tampon to collect the sample.
The other third of women, the control group, only received scheduling assistance.
The team found that mailing the self-collection tests along with helping women book in-clinic appointments improved screening rates twofold, compared with just assisting patients to schedule an appointment.
Screening success among those who received the at-home collection kit was 72%, compared with 37% in the control group.
Of those who received the kits, 78% returned them. This is “impressive,” said Dr. Wang and Dr. Coleman, as previous studies have reported return rates of only 8%-20%.
About 23% of eligible women are overdue for cervical cancer screening by at least a year, according to the National Cancer Institute. Jennifer Smith, PhD, MPH, professor of epidemiology at the University of North Carolina at Chapel Hill and an author of the study, believes every woman deserves equal access to cervical screening.
“I think we really need to make efforts to increase cervical cancer screening among women who are overdue for screening by a year or more from the recommended guidelines,” Dr. Smith said. “We’ve proven along with the wide evidence both in the U.S. and globally that self-collection intervention works well and can motivate screening uptake by breaking down barriers for populations that have less access to care.”
“We’re hoping this research in combination with all of the extensive evidence on the positive performance of HPV self-collection will provide additional information to be considered by the FDA for approval of the kits for primary screening,” Dr. Smith said.
“Government approval of at-home HPV tests would have a huge impact,” said coauthor Noel Brewer, PhD, also of UNC Chapel Hill. “We could better reach those in rural areas where cervical cancer screening is hard to come by.”
Dr. Smith has received research grants, supply donations, and consultancies for Hologic and BD Diagnostics. Dr. Brewer, Dr. Wang, and Dr. Coleman reported no conflicts of interest.
A version of this article first appeared on WebMD.com.
FROM THE LANCET PUBLIC HEALTH
Gestational HTN, preeclampsia worsen long-term risk for ischemic, nonischemic heart failure
, an observational study suggests.
The risks were most pronounced, jumping more than sixfold in the case of ischemic HF, during the first 6 years after the pregnancy. They then receded to plateau at a lower, still significantly elevated level of risk that persisted even years later, in the analysis of women in a Swedish medical birth registry.
The case-matching study compared women with no history of cardiovascular (CV) disease and a first successful pregnancy during which they either developed or did not experience gestational hypertension or preeclampsia.
It’s among the first studies to explore the impact of pregnancy-induced hypertensive disease on subsequent HF risk separately for both ischemic and nonischemic HF and to find that the severity of such risk differs for the two HF etiologies, according to a report published in JACC: Heart Failure.
The adjusted risk for any HF during a median of 13 years after the pregnancy rose 70% for those who had developed gestational hypertension or preeclampsia. Their risk of nonischemic HF went up 60%, and their risk of ischemic HF more than doubled.
Hypertensive disorders of pregnancy “are so much more than short-term disorders confined to the pregnancy period. They have long-term implications throughout a lifetime,” lead author Ängla Mantel, MD, PhD, said in an interview.
Obstetric history doesn’t figure into any formal HF risk scoring systems, observed Dr. Mantel of Karolinska Institutet, Stockholm. Still, women who develop gestational hypertension, preeclampsia, or other pregnancy complications “should be considered a high-risk population even after the pregnancy and monitored for cardiovascular risk factors regularly throughout life.”
In many studies, she said, “knowledge of women-specific risk factors for cardiovascular disease is poor among both clinicians and patients.” The current findings should help raise awareness about such obstetric risk factors for HF, “especially” in patients with HF with preserved ejection fraction (HFpEF), which isn’t closely related to a number of traditional CV risk factors.
Even though pregnancy complications such as gestational hypertension and preeclampsia don’t feature in risk calculators, “they are actually risk enhancers per the 2019 primary prevention guidelines,” Natalie A. Bello, MD, MPH, who was not involved in the current study, said in an interview.
“We’re working to educate physicians and cardiovascular team members to take a pregnancy history” for risk stratification of women in primary prevention,” said Dr. Bello, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles.
The current study, she said, “is an important step” for its finding that hypertensive disorders of pregnancy are associated separately with both ischemic and nonischemic HF.
She pointed out, however, that because the study excluded women with peripartum cardiomyopathy, a form of nonischemic HF, it may “underestimate the impact of hypertensive disorders on the short-term risk of nonischemic heart failure.” Women who had peripartum cardiomyopathy were excluded to avoid misclassification of other HF outcomes, the authors stated.
Also, Dr. Bello said, the study’s inclusion of patients with either gestational hypertension or preeclampsia may complicate its interpretation. Compared with the former condition, she said, preeclampsia “involves more inflammation and more endothelial dysfunction. It may cause a different impact on the heart and the vasculature.”
In the analysis, about 79,000 women with gestational hypertension or preeclampsia were identified among more than 1.4 million primiparous women who entered the Swedish Medical Birth Register over a period of about 30 years. They were matched with about 396,000 women in the registry who had normotensive pregnancies.
Excluded, besides women with peripartum cardiomyopathy, were women with a prepregnancy history of HF, hypertension, ischemic heart disease, atrial fibrillation, or valvular heart disease.
Hazard ratios (HRs) for HF, ischemic HF, and nonischemic HF were significantly elevated over among the women with gestational hypertension or preeclampsia compared to those with normotensive pregnancies:
- Any HF: HR, 1.70 (95% confidence interval [CI], 1.51-1.91)
- Nonischemic HF: HR, 1.60 (95% CI, 1.40-1.83)
- Ischemic HF: HR, 2.28 (95% CI, 1.74-2.98)
The analyses were adjusted for maternal age at delivery, year of delivery, prepregnancy comorbidities, maternal education level, smoking status, and body mass index.
Sharper risk increases were seen among women with gestational hypertension or preeclampsia who delivered prior to gestational week 34:
- Any HF: HR, 2.46 (95% CI, 1.82-3.32)
- Nonischemic HF: HR, 2.33 (95% CI, 1.65-3.31)
- Ischemic HF: HR, 3.64 (95% CI, 1.97-6.74)
Risks for HF developing within 6 years of pregnancy characterized by gestational hypertension or preeclampsia were far more pronounced for ischemic HF than for nonischemic HF:
- Any HF: HR, 2.09 (95% CI, 1.52-2.89)
- Nonischemic HF: HR, 1.86 (95% CI, 1.32-2.61)
- Ischemic HF: HR, 6.52 (95% CI, 2.00-12.34).
The study couldn’t directly explore potential mechanisms for the associations between pregnancy-induced hypertensive disorders and different forms of HF, but it may have provided clues, Dr. Mantel said.
The hypertensive disorders and ischemic HF appear to share risk factors that could lead to both conditions, she noted. Also, hypertension itself is a risk factor for ischemic heart disease.
In contrast, “the risk of nonischemic heart failure might be driven by other factors, such as the inflammatory profile, endothelial dysfunction, and cardiac remodeling induced by preeclampsia or gestational hypertension.”
Those disorders, moreover, are associated with cardiac structural changes that are also seen in HFpEF, Dr. Mantel said. And both HFpEF and preeclampsia are characterized by systemic inflammation and endothelial dysfunction.
“These pathophysiological similarities,” she proposed, “might explain the link between pregnancy-induced hypertensive disorder and HFpEF.”
The authors have disclosed no relevant financial relationships. Dr. Bello has received grants from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
, an observational study suggests.
The risks were most pronounced, jumping more than sixfold in the case of ischemic HF, during the first 6 years after the pregnancy. They then receded to plateau at a lower, still significantly elevated level of risk that persisted even years later, in the analysis of women in a Swedish medical birth registry.
The case-matching study compared women with no history of cardiovascular (CV) disease and a first successful pregnancy during which they either developed or did not experience gestational hypertension or preeclampsia.
It’s among the first studies to explore the impact of pregnancy-induced hypertensive disease on subsequent HF risk separately for both ischemic and nonischemic HF and to find that the severity of such risk differs for the two HF etiologies, according to a report published in JACC: Heart Failure.
The adjusted risk for any HF during a median of 13 years after the pregnancy rose 70% for those who had developed gestational hypertension or preeclampsia. Their risk of nonischemic HF went up 60%, and their risk of ischemic HF more than doubled.
Hypertensive disorders of pregnancy “are so much more than short-term disorders confined to the pregnancy period. They have long-term implications throughout a lifetime,” lead author Ängla Mantel, MD, PhD, said in an interview.
Obstetric history doesn’t figure into any formal HF risk scoring systems, observed Dr. Mantel of Karolinska Institutet, Stockholm. Still, women who develop gestational hypertension, preeclampsia, or other pregnancy complications “should be considered a high-risk population even after the pregnancy and monitored for cardiovascular risk factors regularly throughout life.”
In many studies, she said, “knowledge of women-specific risk factors for cardiovascular disease is poor among both clinicians and patients.” The current findings should help raise awareness about such obstetric risk factors for HF, “especially” in patients with HF with preserved ejection fraction (HFpEF), which isn’t closely related to a number of traditional CV risk factors.
Even though pregnancy complications such as gestational hypertension and preeclampsia don’t feature in risk calculators, “they are actually risk enhancers per the 2019 primary prevention guidelines,” Natalie A. Bello, MD, MPH, who was not involved in the current study, said in an interview.
“We’re working to educate physicians and cardiovascular team members to take a pregnancy history” for risk stratification of women in primary prevention,” said Dr. Bello, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles.
The current study, she said, “is an important step” for its finding that hypertensive disorders of pregnancy are associated separately with both ischemic and nonischemic HF.
She pointed out, however, that because the study excluded women with peripartum cardiomyopathy, a form of nonischemic HF, it may “underestimate the impact of hypertensive disorders on the short-term risk of nonischemic heart failure.” Women who had peripartum cardiomyopathy were excluded to avoid misclassification of other HF outcomes, the authors stated.
Also, Dr. Bello said, the study’s inclusion of patients with either gestational hypertension or preeclampsia may complicate its interpretation. Compared with the former condition, she said, preeclampsia “involves more inflammation and more endothelial dysfunction. It may cause a different impact on the heart and the vasculature.”
In the analysis, about 79,000 women with gestational hypertension or preeclampsia were identified among more than 1.4 million primiparous women who entered the Swedish Medical Birth Register over a period of about 30 years. They were matched with about 396,000 women in the registry who had normotensive pregnancies.
Excluded, besides women with peripartum cardiomyopathy, were women with a prepregnancy history of HF, hypertension, ischemic heart disease, atrial fibrillation, or valvular heart disease.
Hazard ratios (HRs) for HF, ischemic HF, and nonischemic HF were significantly elevated over among the women with gestational hypertension or preeclampsia compared to those with normotensive pregnancies:
- Any HF: HR, 1.70 (95% confidence interval [CI], 1.51-1.91)
- Nonischemic HF: HR, 1.60 (95% CI, 1.40-1.83)
- Ischemic HF: HR, 2.28 (95% CI, 1.74-2.98)
The analyses were adjusted for maternal age at delivery, year of delivery, prepregnancy comorbidities, maternal education level, smoking status, and body mass index.
Sharper risk increases were seen among women with gestational hypertension or preeclampsia who delivered prior to gestational week 34:
- Any HF: HR, 2.46 (95% CI, 1.82-3.32)
- Nonischemic HF: HR, 2.33 (95% CI, 1.65-3.31)
- Ischemic HF: HR, 3.64 (95% CI, 1.97-6.74)
Risks for HF developing within 6 years of pregnancy characterized by gestational hypertension or preeclampsia were far more pronounced for ischemic HF than for nonischemic HF:
- Any HF: HR, 2.09 (95% CI, 1.52-2.89)
- Nonischemic HF: HR, 1.86 (95% CI, 1.32-2.61)
- Ischemic HF: HR, 6.52 (95% CI, 2.00-12.34).
The study couldn’t directly explore potential mechanisms for the associations between pregnancy-induced hypertensive disorders and different forms of HF, but it may have provided clues, Dr. Mantel said.
The hypertensive disorders and ischemic HF appear to share risk factors that could lead to both conditions, she noted. Also, hypertension itself is a risk factor for ischemic heart disease.
In contrast, “the risk of nonischemic heart failure might be driven by other factors, such as the inflammatory profile, endothelial dysfunction, and cardiac remodeling induced by preeclampsia or gestational hypertension.”
Those disorders, moreover, are associated with cardiac structural changes that are also seen in HFpEF, Dr. Mantel said. And both HFpEF and preeclampsia are characterized by systemic inflammation and endothelial dysfunction.
“These pathophysiological similarities,” she proposed, “might explain the link between pregnancy-induced hypertensive disorder and HFpEF.”
The authors have disclosed no relevant financial relationships. Dr. Bello has received grants from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
, an observational study suggests.
The risks were most pronounced, jumping more than sixfold in the case of ischemic HF, during the first 6 years after the pregnancy. They then receded to plateau at a lower, still significantly elevated level of risk that persisted even years later, in the analysis of women in a Swedish medical birth registry.
The case-matching study compared women with no history of cardiovascular (CV) disease and a first successful pregnancy during which they either developed or did not experience gestational hypertension or preeclampsia.
It’s among the first studies to explore the impact of pregnancy-induced hypertensive disease on subsequent HF risk separately for both ischemic and nonischemic HF and to find that the severity of such risk differs for the two HF etiologies, according to a report published in JACC: Heart Failure.
The adjusted risk for any HF during a median of 13 years after the pregnancy rose 70% for those who had developed gestational hypertension or preeclampsia. Their risk of nonischemic HF went up 60%, and their risk of ischemic HF more than doubled.
Hypertensive disorders of pregnancy “are so much more than short-term disorders confined to the pregnancy period. They have long-term implications throughout a lifetime,” lead author Ängla Mantel, MD, PhD, said in an interview.
Obstetric history doesn’t figure into any formal HF risk scoring systems, observed Dr. Mantel of Karolinska Institutet, Stockholm. Still, women who develop gestational hypertension, preeclampsia, or other pregnancy complications “should be considered a high-risk population even after the pregnancy and monitored for cardiovascular risk factors regularly throughout life.”
In many studies, she said, “knowledge of women-specific risk factors for cardiovascular disease is poor among both clinicians and patients.” The current findings should help raise awareness about such obstetric risk factors for HF, “especially” in patients with HF with preserved ejection fraction (HFpEF), which isn’t closely related to a number of traditional CV risk factors.
Even though pregnancy complications such as gestational hypertension and preeclampsia don’t feature in risk calculators, “they are actually risk enhancers per the 2019 primary prevention guidelines,” Natalie A. Bello, MD, MPH, who was not involved in the current study, said in an interview.
“We’re working to educate physicians and cardiovascular team members to take a pregnancy history” for risk stratification of women in primary prevention,” said Dr. Bello, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles.
The current study, she said, “is an important step” for its finding that hypertensive disorders of pregnancy are associated separately with both ischemic and nonischemic HF.
She pointed out, however, that because the study excluded women with peripartum cardiomyopathy, a form of nonischemic HF, it may “underestimate the impact of hypertensive disorders on the short-term risk of nonischemic heart failure.” Women who had peripartum cardiomyopathy were excluded to avoid misclassification of other HF outcomes, the authors stated.
Also, Dr. Bello said, the study’s inclusion of patients with either gestational hypertension or preeclampsia may complicate its interpretation. Compared with the former condition, she said, preeclampsia “involves more inflammation and more endothelial dysfunction. It may cause a different impact on the heart and the vasculature.”
In the analysis, about 79,000 women with gestational hypertension or preeclampsia were identified among more than 1.4 million primiparous women who entered the Swedish Medical Birth Register over a period of about 30 years. They were matched with about 396,000 women in the registry who had normotensive pregnancies.
Excluded, besides women with peripartum cardiomyopathy, were women with a prepregnancy history of HF, hypertension, ischemic heart disease, atrial fibrillation, or valvular heart disease.
Hazard ratios (HRs) for HF, ischemic HF, and nonischemic HF were significantly elevated over among the women with gestational hypertension or preeclampsia compared to those with normotensive pregnancies:
- Any HF: HR, 1.70 (95% confidence interval [CI], 1.51-1.91)
- Nonischemic HF: HR, 1.60 (95% CI, 1.40-1.83)
- Ischemic HF: HR, 2.28 (95% CI, 1.74-2.98)
The analyses were adjusted for maternal age at delivery, year of delivery, prepregnancy comorbidities, maternal education level, smoking status, and body mass index.
Sharper risk increases were seen among women with gestational hypertension or preeclampsia who delivered prior to gestational week 34:
- Any HF: HR, 2.46 (95% CI, 1.82-3.32)
- Nonischemic HF: HR, 2.33 (95% CI, 1.65-3.31)
- Ischemic HF: HR, 3.64 (95% CI, 1.97-6.74)
Risks for HF developing within 6 years of pregnancy characterized by gestational hypertension or preeclampsia were far more pronounced for ischemic HF than for nonischemic HF:
- Any HF: HR, 2.09 (95% CI, 1.52-2.89)
- Nonischemic HF: HR, 1.86 (95% CI, 1.32-2.61)
- Ischemic HF: HR, 6.52 (95% CI, 2.00-12.34).
The study couldn’t directly explore potential mechanisms for the associations between pregnancy-induced hypertensive disorders and different forms of HF, but it may have provided clues, Dr. Mantel said.
The hypertensive disorders and ischemic HF appear to share risk factors that could lead to both conditions, she noted. Also, hypertension itself is a risk factor for ischemic heart disease.
In contrast, “the risk of nonischemic heart failure might be driven by other factors, such as the inflammatory profile, endothelial dysfunction, and cardiac remodeling induced by preeclampsia or gestational hypertension.”
Those disorders, moreover, are associated with cardiac structural changes that are also seen in HFpEF, Dr. Mantel said. And both HFpEF and preeclampsia are characterized by systemic inflammation and endothelial dysfunction.
“These pathophysiological similarities,” she proposed, “might explain the link between pregnancy-induced hypertensive disorder and HFpEF.”
The authors have disclosed no relevant financial relationships. Dr. Bello has received grants from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
FROM JACC: HEART FAILURE
Risk for breast cancer reduced after bariatric surgery
In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.
The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”
The study was published online in JAMA Surgery.
Protective association
To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).
Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.
Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).
In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.
Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.
Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.
There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).
In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).
“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.
Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”
There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
A universal benefit?
“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.
“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.
“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”
Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”
The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”
At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”
The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.
The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”
The study was published online in JAMA Surgery.
Protective association
To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).
Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.
Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).
In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.
Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.
Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.
There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).
In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).
“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.
Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”
There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
A universal benefit?
“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.
“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.
“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”
Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”
The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”
At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”
The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a matched cohort study of more than 69,000 Canadian women, risk for incident breast cancer at 1 year was 40% higher among women who had not undergone bariatric surgery, compared with those who had. The risk remained elevated through 5 years of follow-up.
The findings were “definitely a bit surprising,” study author Aristithes G. Doumouras, MD, MPH, assistant professor of surgery at McMaster University, Hamilton, Ont., said in an interview. “The patients that underwent bariatric surgery had better cancer outcomes than patients who weighed less than they did, so it showed that there was more at play than just weight loss. This effect was durable [and] shows how powerful the surgery is, [as well as] the fact that we haven’t even explored all of its effects.”
The study was published online in JAMA Surgery.
Protective association
To determine whether there is a residual risk for breast cancer following bariatric surgery for obesity, the investigators analyzed clinical and administrative data collected between 2010 and 2016 in Ontario. They retrospectively matched women with obesity who underwent bariatric surgery with women without a history of bariatric surgery. Participants were matched by age and breast cancer screening status. Covariates included diabetes status, neighborhood income quintile, and measures of health care use. The population included 69,260 women (mean age, 45 years).
Among participants who underwent bariatric surgery for obesity, baseline body mass index was greater than 35 for those with related comorbid conditions, and BMI was greater than 40 for those without comorbid conditions. The investigators categorized nonsurgical control patients in accordance with the following four BMI categories: less than 25, 25-29, 30-34, and greater than or equal to 35. Each control group, as well as the surgical group, included 13,852 women.
Participants in the surgical group were followed for 5 years after bariatric surgery. Those in the nonsurgical group were followed for 5 years after the index date (that is, the date of BMI measurement).
In the overall population, 659 cases of breast cancer were diagnosed in the overall population (0.95%) during the study period. This total included 103 (0.74%) cancers in the surgical cohort; 128 (0.92%) in the group with BMI less than 25; 143 (1.03%) among those with BMI 25-29; 150 (1.08%) in the group with BMI 30-34; and 135 (0.97%) among those with BMI greater than or equal to 35.
Most cancers were stage I. There were 65 cases among those with BMI less than 25; 76 for those with BMI of 25-29; 65 for BMI of 30-34; 67 for BMI greater than or equal to 35, and 60 for the surgery group.
Most tumors were of medium grade and were estrogen receptor positive, progesterone receptor positive, and ERBB2 negative. No significant differences were observed across the groups for stage, grade, or hormone status.
There was an increased hazard for incident breast cancer in the nonsurgical group, compared with the postsurgical group after washout periods of 1 year (hazard ratio, 1.40), 2 years (HR, 1.31), and 5 years (HR, 1.38).
In a comparison of the postsurgical cohort with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different for any of the washout periods, but there was a reduced hazard for incident breast cancer among postsurgical patients than among nonsurgical patients in all high BMI categories (BMI ≥ 25).
“Taken together, these results demonstrate that the protective association between substantial weight loss via bariatric surgery and breast cancer risk is sustained after 5 years following surgery and that it is associated with a baseline risk similar to that of women with BMI less than 25,” the investigators write.
Nevertheless, Dr. Doumouras said “the interaction between the surgery and individuals is poorly studied, and this level of personalized medicine is simply not there yet. We are working on developing a prospective cohort that has genetic, protein, and microbiome [data] to help answer these questions.”
There are not enough women in subpopulations such as BRCA carriers to study at this point, he added. “This is where more patients and time will really help the research process.”
A universal benefit?
“Although these findings are important overall for the general population at risk for breast cancer, we raise an important caveat: The benefit of surgical weight loss may not be universal,” write Justin B. Dimick, MD, MPH, surgical innovation editor for JAMA Surgery, and Melissa L. Pilewskie, MD, both of the University of Michigan, Ann Arbor, in an accompanying commentary.
“In addition to lifestyle factors, several nonmodifiable risk factors, such as a genetic predisposition, strong family history, personal history of a high-risk breast lesion, or history of chest wall radiation, impart significant elevation in risk, and the data remain mixed on the impact of weight loss for individuals in these high-risk cohorts,” they add.
“Further study to elucidate the underlying mechanism associated with obesity, weight loss, and breast cancer risk should help guide strategies for risk reduction that are specific to unique high-risk cohorts, because modifiable risk factors may not portend the same benefit among all groups.”
Commenting on the findings, Stephen Edge, MD, breast surgeon and vice president for system quality and outcomes at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., said, “The importance of this study is that it shows that weight loss in midlife can reduce breast cancer risk back to or even below the risk of similar people who were not obese. This has major implications for counseling women.”
The investigators did not have information on the extent of weight loss with surgery or on which participants maintained the lower weight, Dr. Edge noted; “However, overall, most people who have weight reduction surgery have major weight loss.”
At this point, he said, “we can now tell women with obesity that in addition to the many other advantages of weight loss, their risk of getting breast cancer will also be reduced.”
The study was supported by the Ontario Bariatric Registry and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ontario Ministry of Long-Term Care. Dr. Doumouras, Dr. Dimick, Dr. Pilewskie, and Dr. Edge reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY
Does the current age cutoff for screening miss too many cases of cervical cancer in older women?
Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.
EXPERT COMMENTARY
Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)1 We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.2-4
Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.5
Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.6 When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.7
Details of the study
Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.8 They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.
The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.
Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.
Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.
Study strengths and limitations
Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.9
The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.8 And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.4 ●
Cervical cancer is both common and deadly in older women. Although current cervical cancer screening guidelines recommend screening cessation after age 65, remember that this is based on strict exit criteria. Consider screening older women (especially with human papillomavirus [HPV] testing) for cervical cancer if they have risk factors (such as smoking, multiple sexual partners, inconsistent or infrequent screening, history of abnormal Pap or HPV tests), and keep cervical cancer on your differential diagnosis in women who present with postmenopausal bleeding, vaginal discharge, pelvic pain, recurrent urinary tract infections, or other concerning symptoms.
SARAH DILLEY, MD, MPH, AND WARNER HUH, MD
- Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70:321-346. doi:10.3322/caac.21628.
- Dilley S, Huh W, Blechter B, et al. It’s time to re-evaluate cervical cancer screening after age 65. Gynecol Oncol. 2021;162:200-202. doi:10.1016/j.ygyno.2021.04.027.
- Rositch AF, Nowak RG, Gravitt PE. Increased age and racespecific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009. Cancer. 2014;120:2032-2038. doi:10.1002/cncr.28548.
- Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;123:1044-1050. doi:10.1002 /cncr.30507.
- Cancer Stat Facts. National Cancer Institute Surveillance, Epidemiology, and End Results Program. https://seer.cancer .gov/statfacts/html/cervix.html
- Suk R, Hong YR, Rajan SS, et al. Assessment of US Preventive Services Task Force guideline-concordant cervical cancer screening rates and reasons for underscreening by age, race and ethnicity, sexual orientation, rurality, and insurance, 2005 to 2019. JAMA Netw Open. 2022;5:e2143582. doi:10.1001 /jamanetworkopen.2021.43582.
- White MC, Shoemaker ML, Benard VB. Cervical cancer screening and incidence by age: unmet needs near and after the stopping age for screening. Am J Prev Med. 2017;53:392395. doi:10.1016/j.amepre.2017.02.024.
- Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.
- Ortman JM, Velkoff VA, Hogan H. An aging nation: the older population in the United States. May 2014. United States Census Bureau. Accessed April 12, 2023. https://www.census .gov/library/publications/2014/demo/p25-1140.html
Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.
EXPERT COMMENTARY
Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)1 We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.2-4
Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.5
Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.6 When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.7
Details of the study
Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.8 They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.
The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.
Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.
Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.
Study strengths and limitations
Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.9
The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.8 And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.4 ●
Cervical cancer is both common and deadly in older women. Although current cervical cancer screening guidelines recommend screening cessation after age 65, remember that this is based on strict exit criteria. Consider screening older women (especially with human papillomavirus [HPV] testing) for cervical cancer if they have risk factors (such as smoking, multiple sexual partners, inconsistent or infrequent screening, history of abnormal Pap or HPV tests), and keep cervical cancer on your differential diagnosis in women who present with postmenopausal bleeding, vaginal discharge, pelvic pain, recurrent urinary tract infections, or other concerning symptoms.
SARAH DILLEY, MD, MPH, AND WARNER HUH, MD
Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.
EXPERT COMMENTARY
Cervical cancer screening guidelines recommend screening cessation at age 65 once specific exit criteria are met. (According to the American Cancer Society, individuals aged >65 years who have no history of cervical intraepithelial neoplasia [CIN] grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening.)1 We know, however, that about one-fifth of all cervical cancer cases are diagnosed among individuals aged 65 or older, and for Black women that proportion is even higher when data are appropriately adjusted to account for the increased rate of hysterectomy among Black versus White women.2-4
Early-stage cervical cancer is largely a curable disease with very high 5-year overall survival rates. Unfortunately, more than half of all cervical cancer is diagnosed at a more advanced stage, and survival rates are much lower for this population.5
Cervical cancer incidence rates plummeted in the United States after the introduction of the Pap test for cervical cancer screening. However, the percentage of women who are not up to date with cervical cancer screening may now be increasing, from 14% in 2005 to 23% in 2019 according to one study from the US Preventive Services Task Force.6 When looking at cervical cancer screening rates by age, researchers from the Centers for Disease Control and Prevention estimate that the proportion of patients who have not been recently screened goes up as patients get older, with approximately 845,000 American women aged 61 to 65 not adequately screened in 2015 alone.7
Details of the study
Cooley and colleagues sought to better characterize the cohort of women diagnosed with cervical cancer at a later age, specifically the stage at diagnosis and survival.8 They used data from the California Cancer Registry (CCR), a large state-mandated, population-based data repository that is affiliated with the Surveillance, Epidemiology, and End Results (SEER) program.
The researchers identified 12,442 womenin the CCR who were newly diagnosed with cervical cancer from 2009 to 2018, 17.4% of whom were age 65 or older. They looked at cancer stage at diagnosis as it relates to relative survival rate (“the ratio of the observed survival rate among those who have cancer divided by the expected survival rate for people of the same sex, race/ethnicity, and age who do not have cancer”), Charlson comorbidity score, socioeconomic status, health insurance status, urbanicity, and race/ethnicity.
Results. In this study, 71% of women aged 65 or older presented with advanced-stage disease (FIGO [International Federation of Gynecology and Obstetrics] stage II–IV) as compared with only 48% in those aged 21 to 64. Five-year relative survival rates also were lower in the older cohort—23% to 37%, compared with 42% to 52% in the younger patients. In a sensitivity analysis, late-stage disease was associated with older age, increasing medical comorbidities, and nonadenocarcinoma histology.
Interestingly, older women of Hispanic ethnicity were less likely to be diagnosed with late-stage disease when compared with non-Hispanic White women.
Study strengths and limitations
Although this study’s conclusions—that patients with advanced-stage cancer are more likely to do poorly than those with early-stage cancer—may seem obvious to some even without the proven data, it is still important to highlight what a clinician may intuit with data to support that intuition. It is particularly important to emphasize this risk in older women in light of the aging population in the United States, with adults older than age 65 expected to account for more than 20% of the nation’s population by 2030.9
The study by Cooley and colleagues adds value to the existing literature due to its large study population, which included more than 12,000 patients diagnosed with cervical cancer.8 And although its results may not be completely generalizable as the data were gathered from only a California-specific population, the sample was diverse with significant portions of Hispanic and Black patients. This study supports previous data that showed high rates of advanced cervical cancer in women older than age 65, with resultant worse 5-year relative survival in this population of older women specifically.4 ●
Cervical cancer is both common and deadly in older women. Although current cervical cancer screening guidelines recommend screening cessation after age 65, remember that this is based on strict exit criteria. Consider screening older women (especially with human papillomavirus [HPV] testing) for cervical cancer if they have risk factors (such as smoking, multiple sexual partners, inconsistent or infrequent screening, history of abnormal Pap or HPV tests), and keep cervical cancer on your differential diagnosis in women who present with postmenopausal bleeding, vaginal discharge, pelvic pain, recurrent urinary tract infections, or other concerning symptoms.
SARAH DILLEY, MD, MPH, AND WARNER HUH, MD
- Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70:321-346. doi:10.3322/caac.21628.
- Dilley S, Huh W, Blechter B, et al. It’s time to re-evaluate cervical cancer screening after age 65. Gynecol Oncol. 2021;162:200-202. doi:10.1016/j.ygyno.2021.04.027.
- Rositch AF, Nowak RG, Gravitt PE. Increased age and racespecific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009. Cancer. 2014;120:2032-2038. doi:10.1002/cncr.28548.
- Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;123:1044-1050. doi:10.1002 /cncr.30507.
- Cancer Stat Facts. National Cancer Institute Surveillance, Epidemiology, and End Results Program. https://seer.cancer .gov/statfacts/html/cervix.html
- Suk R, Hong YR, Rajan SS, et al. Assessment of US Preventive Services Task Force guideline-concordant cervical cancer screening rates and reasons for underscreening by age, race and ethnicity, sexual orientation, rurality, and insurance, 2005 to 2019. JAMA Netw Open. 2022;5:e2143582. doi:10.1001 /jamanetworkopen.2021.43582.
- White MC, Shoemaker ML, Benard VB. Cervical cancer screening and incidence by age: unmet needs near and after the stopping age for screening. Am J Prev Med. 2017;53:392395. doi:10.1016/j.amepre.2017.02.024.
- Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.
- Ortman JM, Velkoff VA, Hogan H. An aging nation: the older population in the United States. May 2014. United States Census Bureau. Accessed April 12, 2023. https://www.census .gov/library/publications/2014/demo/p25-1140.html
- Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70:321-346. doi:10.3322/caac.21628.
- Dilley S, Huh W, Blechter B, et al. It’s time to re-evaluate cervical cancer screening after age 65. Gynecol Oncol. 2021;162:200-202. doi:10.1016/j.ygyno.2021.04.027.
- Rositch AF, Nowak RG, Gravitt PE. Increased age and racespecific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009. Cancer. 2014;120:2032-2038. doi:10.1002/cncr.28548.
- Beavis AL, Gravitt PE, Rositch AF. Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States. Cancer. 2017;123:1044-1050. doi:10.1002 /cncr.30507.
- Cancer Stat Facts. National Cancer Institute Surveillance, Epidemiology, and End Results Program. https://seer.cancer .gov/statfacts/html/cervix.html
- Suk R, Hong YR, Rajan SS, et al. Assessment of US Preventive Services Task Force guideline-concordant cervical cancer screening rates and reasons for underscreening by age, race and ethnicity, sexual orientation, rurality, and insurance, 2005 to 2019. JAMA Netw Open. 2022;5:e2143582. doi:10.1001 /jamanetworkopen.2021.43582.
- White MC, Shoemaker ML, Benard VB. Cervical cancer screening and incidence by age: unmet needs near and after the stopping age for screening. Am J Prev Med. 2017;53:392395. doi:10.1016/j.amepre.2017.02.024.
- Cooley JJ, Maguire FB, Morris CR, et al. Cervical cancer stage at diagnosis and survival among women ≥65 years in California. Cancer Epidemiol Biomarkers Prev. 2023;32:91-97. doi:10.1158/1055-9965.EPI-22-0793.
- Ortman JM, Velkoff VA, Hogan H. An aging nation: the older population in the United States. May 2014. United States Census Bureau. Accessed April 12, 2023. https://www.census .gov/library/publications/2014/demo/p25-1140.html
Does hormone replacement therapy prevent cognitive decline in postmenopausal women?
Evidence summary
Multiple analyses suggest HRT worsens rather than improves cognition
A 2017 Cochrane review of 22 randomized, double-blind studies compared use of HRT (estrogen only or combination estrogen + progesterone therapies) with placebo in postmenopausal women (N = 43,637). Age ranges varied, but the average age in most studies was > 60 years. Treatment duration was at least 1 year. Various outcomes were assessed across these 22 studies, including cardiovascular disease, bone health, and cognition.1
Cognitive outcomes were assessed with the Mini-Mental Status Exam in 5 of the trials (N = 12,789). Data were not combined due to heterogeneity. The authors found no significant difference in cognitive scores between the treatment and control groups in any of these 5 studies.1
In the largest included study, the Women’s Health Initiative (WHI) Memory Study (N = 10,739), participants were older than 65 years. Among those receiving estrogen-only HRT, there were no statistically significant differences compared to those receiving placebo. However, healthy postmenopausal women taking combination HRT had an increased risk for “probable dementia” compared to those taking placebo (relative risk [RR] = 1.97; 95% CI, 1.16-3.33). When researchers looked exclusively at women taking HRT, the risk for dementia increased from 9 in 1000 to 18 in 1000 (95% CI, 11-30) after 4 years of HRT use. This results in a number needed to harm of 4 to 50 patients.1
Two notable limitations of this evidence are that the average age of this population was > 60 years and 80% of the participants were White.1
A 2021 meta-analysis of 23 RCTs (N = 13,683) studied the effect of HRT on global cognitive function as well as specific cognitive domains including memory, executive function, attention, and language. Mean patient age in the studies varied from 48 to 81 years. Nine of these studies were also included in the previously discussed Cochrane review.2
There was a statistically significant but small decrease in overall global cognition (10 trials; N = 12,115; standardized mean difference [SMD] = –0.04; 95% CI, –0.08 to –0.01) in those receiving HRT compared to placebo. This effect was slightly more pronounced among those who initiated HRT at age > 60 years (8 trials; N = 11,914; SMD = –0.05; 95% CI, –0.08 to –0.01) and among patients with HRT duration > 6 months (7 trials; N = 11,828; SMD = –0.05; 95% CI, –0.08 to –0.01). There were no significant differences in specific cognitive domains.2
In a 2017 follow-up to the WHI trial, researchers analyzed data on long-term cognitive effects in women previously treated with HRT. There were 2 cohorts: participants who initiated HRT at a younger age (50-54; N = 1376) and those who initiated HRT later in life (age 65-79; N = 2880). Cognitive outcomes were assessed using the Telephone Interview for Cognitive Status-modified, with interviews conducted annually beginning 6 to 7 years after HRT was stopped.3
The investigators found no significant change in composite cognitive function in the younger HRT-treated group compared to placebo (estrogen alone: mean deviation [MD] = 0.014; 95% CI, –0.097 to 0.126; estrogen + progesterone: MD = –0.047; 95% CI, –0.134 to 0.04), or in the group who initiated HRT at an older age (estrogen alone: MD = –0.099; 95% CI, –0.202 to 0.004; estrogen + progesterone: MD = –0.022; 95% CI, –0.099 to 0.055). The authors state that although the data did not reach significance, this study also found a trend toward decreases in global cognitive function in the older age group.3
Editor’s takeaway
Abundant, consistent evidence with long-term follow-up shows postmenopausal HRT does not reduce cognitive decline. In fact, it appears to increase cognitive decline slightly. Renewed interest in postmenopausal HRT to alleviate menopausal symptoms should balance the risks and benefits to the individual patient.
1. Marjoribanks J, Farquhar C, Roberts H, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1:CD004143. doi: 10.1002/14651858.CD004143.pub5
2. Zhou HH, Yu Z, Luo L, et al. The effect of hormone replacement therapy on cognitive function in healthy postmenopausal women: a meta-analysis of 23 randomized controlled trials. Psychogeriatrics. 2021;21:926-938. doi: 10.1111/psyg.12768
3. Espeland MA, Rapp SR, Manson JE, et al. Long-term effects on cognitive trajectories of postmenopausal hormone therapy in two age groups. J Gerontol A Biol Sci Med Sci. 2017;72:838-845. doi: 10.1093/gerona/glw156
Evidence summary
Multiple analyses suggest HRT worsens rather than improves cognition
A 2017 Cochrane review of 22 randomized, double-blind studies compared use of HRT (estrogen only or combination estrogen + progesterone therapies) with placebo in postmenopausal women (N = 43,637). Age ranges varied, but the average age in most studies was > 60 years. Treatment duration was at least 1 year. Various outcomes were assessed across these 22 studies, including cardiovascular disease, bone health, and cognition.1
Cognitive outcomes were assessed with the Mini-Mental Status Exam in 5 of the trials (N = 12,789). Data were not combined due to heterogeneity. The authors found no significant difference in cognitive scores between the treatment and control groups in any of these 5 studies.1
In the largest included study, the Women’s Health Initiative (WHI) Memory Study (N = 10,739), participants were older than 65 years. Among those receiving estrogen-only HRT, there were no statistically significant differences compared to those receiving placebo. However, healthy postmenopausal women taking combination HRT had an increased risk for “probable dementia” compared to those taking placebo (relative risk [RR] = 1.97; 95% CI, 1.16-3.33). When researchers looked exclusively at women taking HRT, the risk for dementia increased from 9 in 1000 to 18 in 1000 (95% CI, 11-30) after 4 years of HRT use. This results in a number needed to harm of 4 to 50 patients.1
Two notable limitations of this evidence are that the average age of this population was > 60 years and 80% of the participants were White.1
A 2021 meta-analysis of 23 RCTs (N = 13,683) studied the effect of HRT on global cognitive function as well as specific cognitive domains including memory, executive function, attention, and language. Mean patient age in the studies varied from 48 to 81 years. Nine of these studies were also included in the previously discussed Cochrane review.2
There was a statistically significant but small decrease in overall global cognition (10 trials; N = 12,115; standardized mean difference [SMD] = –0.04; 95% CI, –0.08 to –0.01) in those receiving HRT compared to placebo. This effect was slightly more pronounced among those who initiated HRT at age > 60 years (8 trials; N = 11,914; SMD = –0.05; 95% CI, –0.08 to –0.01) and among patients with HRT duration > 6 months (7 trials; N = 11,828; SMD = –0.05; 95% CI, –0.08 to –0.01). There were no significant differences in specific cognitive domains.2
In a 2017 follow-up to the WHI trial, researchers analyzed data on long-term cognitive effects in women previously treated with HRT. There were 2 cohorts: participants who initiated HRT at a younger age (50-54; N = 1376) and those who initiated HRT later in life (age 65-79; N = 2880). Cognitive outcomes were assessed using the Telephone Interview for Cognitive Status-modified, with interviews conducted annually beginning 6 to 7 years after HRT was stopped.3
The investigators found no significant change in composite cognitive function in the younger HRT-treated group compared to placebo (estrogen alone: mean deviation [MD] = 0.014; 95% CI, –0.097 to 0.126; estrogen + progesterone: MD = –0.047; 95% CI, –0.134 to 0.04), or in the group who initiated HRT at an older age (estrogen alone: MD = –0.099; 95% CI, –0.202 to 0.004; estrogen + progesterone: MD = –0.022; 95% CI, –0.099 to 0.055). The authors state that although the data did not reach significance, this study also found a trend toward decreases in global cognitive function in the older age group.3
Editor’s takeaway
Abundant, consistent evidence with long-term follow-up shows postmenopausal HRT does not reduce cognitive decline. In fact, it appears to increase cognitive decline slightly. Renewed interest in postmenopausal HRT to alleviate menopausal symptoms should balance the risks and benefits to the individual patient.
Evidence summary
Multiple analyses suggest HRT worsens rather than improves cognition
A 2017 Cochrane review of 22 randomized, double-blind studies compared use of HRT (estrogen only or combination estrogen + progesterone therapies) with placebo in postmenopausal women (N = 43,637). Age ranges varied, but the average age in most studies was > 60 years. Treatment duration was at least 1 year. Various outcomes were assessed across these 22 studies, including cardiovascular disease, bone health, and cognition.1
Cognitive outcomes were assessed with the Mini-Mental Status Exam in 5 of the trials (N = 12,789). Data were not combined due to heterogeneity. The authors found no significant difference in cognitive scores between the treatment and control groups in any of these 5 studies.1
In the largest included study, the Women’s Health Initiative (WHI) Memory Study (N = 10,739), participants were older than 65 years. Among those receiving estrogen-only HRT, there were no statistically significant differences compared to those receiving placebo. However, healthy postmenopausal women taking combination HRT had an increased risk for “probable dementia” compared to those taking placebo (relative risk [RR] = 1.97; 95% CI, 1.16-3.33). When researchers looked exclusively at women taking HRT, the risk for dementia increased from 9 in 1000 to 18 in 1000 (95% CI, 11-30) after 4 years of HRT use. This results in a number needed to harm of 4 to 50 patients.1
Two notable limitations of this evidence are that the average age of this population was > 60 years and 80% of the participants were White.1
A 2021 meta-analysis of 23 RCTs (N = 13,683) studied the effect of HRT on global cognitive function as well as specific cognitive domains including memory, executive function, attention, and language. Mean patient age in the studies varied from 48 to 81 years. Nine of these studies were also included in the previously discussed Cochrane review.2
There was a statistically significant but small decrease in overall global cognition (10 trials; N = 12,115; standardized mean difference [SMD] = –0.04; 95% CI, –0.08 to –0.01) in those receiving HRT compared to placebo. This effect was slightly more pronounced among those who initiated HRT at age > 60 years (8 trials; N = 11,914; SMD = –0.05; 95% CI, –0.08 to –0.01) and among patients with HRT duration > 6 months (7 trials; N = 11,828; SMD = –0.05; 95% CI, –0.08 to –0.01). There were no significant differences in specific cognitive domains.2
In a 2017 follow-up to the WHI trial, researchers analyzed data on long-term cognitive effects in women previously treated with HRT. There were 2 cohorts: participants who initiated HRT at a younger age (50-54; N = 1376) and those who initiated HRT later in life (age 65-79; N = 2880). Cognitive outcomes were assessed using the Telephone Interview for Cognitive Status-modified, with interviews conducted annually beginning 6 to 7 years after HRT was stopped.3
The investigators found no significant change in composite cognitive function in the younger HRT-treated group compared to placebo (estrogen alone: mean deviation [MD] = 0.014; 95% CI, –0.097 to 0.126; estrogen + progesterone: MD = –0.047; 95% CI, –0.134 to 0.04), or in the group who initiated HRT at an older age (estrogen alone: MD = –0.099; 95% CI, –0.202 to 0.004; estrogen + progesterone: MD = –0.022; 95% CI, –0.099 to 0.055). The authors state that although the data did not reach significance, this study also found a trend toward decreases in global cognitive function in the older age group.3
Editor’s takeaway
Abundant, consistent evidence with long-term follow-up shows postmenopausal HRT does not reduce cognitive decline. In fact, it appears to increase cognitive decline slightly. Renewed interest in postmenopausal HRT to alleviate menopausal symptoms should balance the risks and benefits to the individual patient.
1. Marjoribanks J, Farquhar C, Roberts H, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1:CD004143. doi: 10.1002/14651858.CD004143.pub5
2. Zhou HH, Yu Z, Luo L, et al. The effect of hormone replacement therapy on cognitive function in healthy postmenopausal women: a meta-analysis of 23 randomized controlled trials. Psychogeriatrics. 2021;21:926-938. doi: 10.1111/psyg.12768
3. Espeland MA, Rapp SR, Manson JE, et al. Long-term effects on cognitive trajectories of postmenopausal hormone therapy in two age groups. J Gerontol A Biol Sci Med Sci. 2017;72:838-845. doi: 10.1093/gerona/glw156
1. Marjoribanks J, Farquhar C, Roberts H, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1:CD004143. doi: 10.1002/14651858.CD004143.pub5
2. Zhou HH, Yu Z, Luo L, et al. The effect of hormone replacement therapy on cognitive function in healthy postmenopausal women: a meta-analysis of 23 randomized controlled trials. Psychogeriatrics. 2021;21:926-938. doi: 10.1111/psyg.12768
3. Espeland MA, Rapp SR, Manson JE, et al. Long-term effects on cognitive trajectories of postmenopausal hormone therapy in two age groups. J Gerontol A Biol Sci Med Sci. 2017;72:838-845. doi: 10.1093/gerona/glw156
EVIDENCE-BASED REVIEW:
NO. Hormone replacement therapy (HRT) does not prevent cognitive decline in postmenopausal women—and in fact, it may slightly increase risk (strength of recommendation, A; systematic review, meta-analysis of randomized controlled trials [RCTs], and individual RCT).
FDA approves new drug to manage menopausal hot flashes
The Food and Drug Administration has approved the oral medication fezolinetant (Veozah) for the treatment of moderate to severe hot flashes in menopausal women, according to an FDA statement. The approved dose is 45 mg once daily.
Fezolinetant, a neurokinin 3 (NK3) receptor antagonist, is the first drug of its kind to earn FDA approval for the vasomotor symptoms associated with menopause, according to the statement. The drug works by binding to the NK3 receptor, which plays a role in regulating body temperature, and blocking its activity. Fezolinetant is not a hormone, and can be taken by women for whom hormones are contraindicated, such as those with a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease, the FDA stated.
The approval was based on data from the SKYLIGHT 2 trial, results of which were presented at the annual meeting of the Endocrine Society, reported by this news organization, and published in the Journal of Clinical Endocrinology and Metabolism.
In the two-phase trial, women were randomized to 30 mg or 45 mg of fezolinetant or a placebo. After 12 weeks, women in placebo groups were rerandomized to fezolinetant for a 40-week safety study.
The study population included women aged 40-65 years, with an average minimum of seven moderate-to-severe hot flashes per day. The study included 120 sites in North America and Europe.
At 12 weeks, both placebo and fezolinetant patients experienced reductions in moderate to severe vasomotor symptoms of approximately 60%, as well as a significant decrease in vasomotor symptom severity.
The FDA statement noted that patients should undergo baseline blood work before starting fezolinetant to test for liver infection or damage, and the prescribing information includes a warning for liver injury; blood work should be repeated at 3, 6, and 9 months after starting the medication, according to the FDA and a press release from the manufacturer Astellas.
The most common side effects associated with fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated liver values, according to the FDA statement. The FDA granted Astellas Pharma’s application a Priority Review designation. Astellas has priced the drug at $550 for a 30-day supply, significantly higher than the Institute for Clinical and Economic Review’s previously recommended range of $2,000 to $2,500 per year.
Full prescribing information is available here.
The Food and Drug Administration has approved the oral medication fezolinetant (Veozah) for the treatment of moderate to severe hot flashes in menopausal women, according to an FDA statement. The approved dose is 45 mg once daily.
Fezolinetant, a neurokinin 3 (NK3) receptor antagonist, is the first drug of its kind to earn FDA approval for the vasomotor symptoms associated with menopause, according to the statement. The drug works by binding to the NK3 receptor, which plays a role in regulating body temperature, and blocking its activity. Fezolinetant is not a hormone, and can be taken by women for whom hormones are contraindicated, such as those with a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease, the FDA stated.
The approval was based on data from the SKYLIGHT 2 trial, results of which were presented at the annual meeting of the Endocrine Society, reported by this news organization, and published in the Journal of Clinical Endocrinology and Metabolism.
In the two-phase trial, women were randomized to 30 mg or 45 mg of fezolinetant or a placebo. After 12 weeks, women in placebo groups were rerandomized to fezolinetant for a 40-week safety study.
The study population included women aged 40-65 years, with an average minimum of seven moderate-to-severe hot flashes per day. The study included 120 sites in North America and Europe.
At 12 weeks, both placebo and fezolinetant patients experienced reductions in moderate to severe vasomotor symptoms of approximately 60%, as well as a significant decrease in vasomotor symptom severity.
The FDA statement noted that patients should undergo baseline blood work before starting fezolinetant to test for liver infection or damage, and the prescribing information includes a warning for liver injury; blood work should be repeated at 3, 6, and 9 months after starting the medication, according to the FDA and a press release from the manufacturer Astellas.
The most common side effects associated with fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated liver values, according to the FDA statement. The FDA granted Astellas Pharma’s application a Priority Review designation. Astellas has priced the drug at $550 for a 30-day supply, significantly higher than the Institute for Clinical and Economic Review’s previously recommended range of $2,000 to $2,500 per year.
Full prescribing information is available here.
The Food and Drug Administration has approved the oral medication fezolinetant (Veozah) for the treatment of moderate to severe hot flashes in menopausal women, according to an FDA statement. The approved dose is 45 mg once daily.
Fezolinetant, a neurokinin 3 (NK3) receptor antagonist, is the first drug of its kind to earn FDA approval for the vasomotor symptoms associated with menopause, according to the statement. The drug works by binding to the NK3 receptor, which plays a role in regulating body temperature, and blocking its activity. Fezolinetant is not a hormone, and can be taken by women for whom hormones are contraindicated, such as those with a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease, the FDA stated.
The approval was based on data from the SKYLIGHT 2 trial, results of which were presented at the annual meeting of the Endocrine Society, reported by this news organization, and published in the Journal of Clinical Endocrinology and Metabolism.
In the two-phase trial, women were randomized to 30 mg or 45 mg of fezolinetant or a placebo. After 12 weeks, women in placebo groups were rerandomized to fezolinetant for a 40-week safety study.
The study population included women aged 40-65 years, with an average minimum of seven moderate-to-severe hot flashes per day. The study included 120 sites in North America and Europe.
At 12 weeks, both placebo and fezolinetant patients experienced reductions in moderate to severe vasomotor symptoms of approximately 60%, as well as a significant decrease in vasomotor symptom severity.
The FDA statement noted that patients should undergo baseline blood work before starting fezolinetant to test for liver infection or damage, and the prescribing information includes a warning for liver injury; blood work should be repeated at 3, 6, and 9 months after starting the medication, according to the FDA and a press release from the manufacturer Astellas.
The most common side effects associated with fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated liver values, according to the FDA statement. The FDA granted Astellas Pharma’s application a Priority Review designation. Astellas has priced the drug at $550 for a 30-day supply, significantly higher than the Institute for Clinical and Economic Review’s previously recommended range of $2,000 to $2,500 per year.
Full prescribing information is available here.
What BP target is appropriate for pregnant patients with mild chronic hypertension?
ILLUSTRATIVE CASE
A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?
Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.4 Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.3
Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.2 Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.
STUDY SUMMARY
Active BP treatment yielded better pregnancy outcomes
In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.
First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.
Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.
WHAT’S NEW
Target BP of < 140/90 mm Hg reduced risk
This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.8,9
Continue to: CAVEATS
CAVEATS
Patient characteristics and medication choices were limited
This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.
Most patients in the trial who required medications received labetalol or extended-release nifedipine. It is unclear if other medications would produce similar outcomes.
CHALLENGES TO IMPLEMENTATION
Limited challenges anticipated
There should be limited challenges to implementation.
1. Tita AT, Szychowski JM, Boggess K, et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133:e26-e50. doi: 10.1097/AOG.0000000000003020
3. Guedes-Martins L. Chronic hypertension and pregnancy. Adv Exp Med Biol. 2017;956:395-407. doi: 10.1007/5584_2016_81
4. Bramham K, Parnell B, Nelson-Piercy C, et al. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2014;348:g2301. doi: 10.1136/bmj.g2301
5. Sibai BM, Mabie WC, Shamsa F, et al. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynecol. 1990;162:960-967. doi: 10.1016/0002-9378(90)91297-p
6. Gruppo di Studio Ipertensione in Gravidanza. Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. Br J Obstet Gynaecol. 1998;105:718-722. doi: 10.1111/j.1471-0528.1998.tb10201.x
7. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372:407-417. doi: 10.1056/NEJMoa1404595
8. American College of Obstetricians and Gynecologists’ Committee on Clinical Practice Guidelines—Obstetrics. Clinical guidance for the integration of the findings of the Chronic Hypertension and Pregnancy (CHAP) study. Practice Advisory. April 2022. Accessed December 4, 2022. www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/04/clinical-guidance-for-the-integration-of-the-findings-of-the-chronic-hypertension-and-pregnancy-chap-study
9. Society for Maternal-Fetal Medicine; Publications Committee. Society for Maternal-Fetal Medicine statement: antihypertensive therapy for mild chronic hypertension in pregnancy—the Chronic Hypertension and Pregnancy trial. Am J Obstet Gynecol. 2022;227:B24-B27. doi: 10.1016/j.ajog.2022.04.011
ILLUSTRATIVE CASE
A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?
Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.4 Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.3
Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.2 Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.
STUDY SUMMARY
Active BP treatment yielded better pregnancy outcomes
In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.
First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.
Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.
WHAT’S NEW
Target BP of < 140/90 mm Hg reduced risk
This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.8,9
Continue to: CAVEATS
CAVEATS
Patient characteristics and medication choices were limited
This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.
Most patients in the trial who required medications received labetalol or extended-release nifedipine. It is unclear if other medications would produce similar outcomes.
CHALLENGES TO IMPLEMENTATION
Limited challenges anticipated
There should be limited challenges to implementation.
ILLUSTRATIVE CASE
A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?
Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.4 Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.3
Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.2 Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.
STUDY SUMMARY
Active BP treatment yielded better pregnancy outcomes
In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.
First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.
Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.
WHAT’S NEW
Target BP of < 140/90 mm Hg reduced risk
This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.8,9
Continue to: CAVEATS
CAVEATS
Patient characteristics and medication choices were limited
This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.
Most patients in the trial who required medications received labetalol or extended-release nifedipine. It is unclear if other medications would produce similar outcomes.
CHALLENGES TO IMPLEMENTATION
Limited challenges anticipated
There should be limited challenges to implementation.
1. Tita AT, Szychowski JM, Boggess K, et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133:e26-e50. doi: 10.1097/AOG.0000000000003020
3. Guedes-Martins L. Chronic hypertension and pregnancy. Adv Exp Med Biol. 2017;956:395-407. doi: 10.1007/5584_2016_81
4. Bramham K, Parnell B, Nelson-Piercy C, et al. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2014;348:g2301. doi: 10.1136/bmj.g2301
5. Sibai BM, Mabie WC, Shamsa F, et al. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynecol. 1990;162:960-967. doi: 10.1016/0002-9378(90)91297-p
6. Gruppo di Studio Ipertensione in Gravidanza. Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. Br J Obstet Gynaecol. 1998;105:718-722. doi: 10.1111/j.1471-0528.1998.tb10201.x
7. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372:407-417. doi: 10.1056/NEJMoa1404595
8. American College of Obstetricians and Gynecologists’ Committee on Clinical Practice Guidelines—Obstetrics. Clinical guidance for the integration of the findings of the Chronic Hypertension and Pregnancy (CHAP) study. Practice Advisory. April 2022. Accessed December 4, 2022. www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/04/clinical-guidance-for-the-integration-of-the-findings-of-the-chronic-hypertension-and-pregnancy-chap-study
9. Society for Maternal-Fetal Medicine; Publications Committee. Society for Maternal-Fetal Medicine statement: antihypertensive therapy for mild chronic hypertension in pregnancy—the Chronic Hypertension and Pregnancy trial. Am J Obstet Gynecol. 2022;227:B24-B27. doi: 10.1016/j.ajog.2022.04.011
1. Tita AT, Szychowski JM, Boggess K, et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133:e26-e50. doi: 10.1097/AOG.0000000000003020
3. Guedes-Martins L. Chronic hypertension and pregnancy. Adv Exp Med Biol. 2017;956:395-407. doi: 10.1007/5584_2016_81
4. Bramham K, Parnell B, Nelson-Piercy C, et al. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2014;348:g2301. doi: 10.1136/bmj.g2301
5. Sibai BM, Mabie WC, Shamsa F, et al. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Am J Obstet Gynecol. 1990;162:960-967. doi: 10.1016/0002-9378(90)91297-p
6. Gruppo di Studio Ipertensione in Gravidanza. Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. Br J Obstet Gynaecol. 1998;105:718-722. doi: 10.1111/j.1471-0528.1998.tb10201.x
7. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372:407-417. doi: 10.1056/NEJMoa1404595
8. American College of Obstetricians and Gynecologists’ Committee on Clinical Practice Guidelines—Obstetrics. Clinical guidance for the integration of the findings of the Chronic Hypertension and Pregnancy (CHAP) study. Practice Advisory. April 2022. Accessed December 4, 2022. www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/04/clinical-guidance-for-the-integration-of-the-findings-of-the-chronic-hypertension-and-pregnancy-chap-study
9. Society for Maternal-Fetal Medicine; Publications Committee. Society for Maternal-Fetal Medicine statement: antihypertensive therapy for mild chronic hypertension in pregnancy—the Chronic Hypertension and Pregnancy trial. Am J Obstet Gynecol. 2022;227:B24-B27. doi: 10.1016/j.ajog.2022.04.011
PRACTICE CHANGER
Treat mild chronic hypertension during pregnancy to a target of < 140/90 mm Hg to reduce the risk for adverse pregnancy outcomes.
STRENGTH OF RECOMMENDATION
B: Based on a single high-quality randomized controlled trial (RCT).1
Tita AT, Szychowski JM, Boggess K, et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386:1781-1792. doi: 10.1056/NEJMoa2201295
BMI has greater impact on survival in younger breast cancer patients
new data suggest.
Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.
Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.
The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.
Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (30 kg/m2 or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.
DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).
“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.
In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.
The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.
In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.
When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
Data draw attention to quality of life and lifestyle factors
The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.
Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.
Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.
“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.
The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.
new data suggest.
Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.
Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.
The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.
Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (30 kg/m2 or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.
DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).
“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.
In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.
The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.
In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.
When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
Data draw attention to quality of life and lifestyle factors
The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.
Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.
Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.
“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.
The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.
new data suggest.
Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.
Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.
The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.
Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (30 kg/m2 or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.
DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).
“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.
In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.
The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.
In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.
When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
Data draw attention to quality of life and lifestyle factors
The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.
Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.
Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.
“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.
The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.
FROM ESMO BREAST CANCER 2023