What are the major manifestations of congenital rubella syndrome?

Continue to the answer...

Rubella is one of the most highly teratogenic of all the viral infections, particularly when maternal infection occurs in the first trimester. Manifestations of congenital rubella include hearing deficits, cataracts, glaucoma, microcephaly, mental retardation, cardiac malformations such as patent ductus arteriosus and pulmonic stenosis, and growth restriction.

What are the major manifestations of congenital rubella syndrome?

Continue to the answer...

Rubella is one of the most highly teratogenic of all the viral infections, particularly when maternal infection occurs in the first trimester. Manifestations of congenital rubella include hearing deficits, cataracts, glaucoma, microcephaly, mental retardation, cardiac malformations such as patent ductus arteriosus and pulmonic stenosis, and growth restriction.

What are the major manifestations of congenital rubella syndrome?

Continue to the answer...

Rubella is one of the most highly teratogenic of all the viral infections, particularly when maternal infection occurs in the first trimester. Manifestations of congenital rubella include hearing deficits, cataracts, glaucoma, microcephaly, mental retardation, cardiac malformations such as patent ductus arteriosus and pulmonic stenosis, and growth restriction.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Pinker or redder actinic keratoses (AKs) indicate greater inflammation, according to a retrospective study that analyzed images and histopathology slides of 49 actinic keratosis lesions.

Data suggest that up to 65% of squamous cell carcinomas (SCCs) were at some point diagnosed as AKs, wrote Jessica G. Labadie, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues. Early identification of AKs is important to prevent progression to SCCs; previous studies have used histology or morphology, but not color, to characterize AK lesions, they said. In the study published in Dermatologic Surgery, the researchers analyzed images and histopathology slides to characterize AKs by color and to examine associations with inflammation and vasculature. They identified AKs from patients diagnosed between January 2018 and October 2019. The lesions were classified as white (4), brown (9), red (15), or pink (21).

Overall, white AKs had an absence of erythema and were significantly less likely to show inflammation on histopathology, compared with other colors. Brown AKs showed no significant increase in vascularity, but were significantly associated with pigment incontinence, basilar pigment presence, and absence of inflammation.

Notably, dermoscopy of red AKs revealed a distinctive polymorphous vessel pattern in most samples, as well as erythema in all. Similarly, all pink AKs showed erythema, and all showed inflammatory infiltrate on histology, although most did not show increased vascularity.

For all colors of AKs, there was a significant association between the presence of erythema on dermoscopy and the presence of inflammation on histology, while the absence of erythema on dermoscopy corresponded to a significant absence of inflammation on histology, the researchers noted.

“This report adds to the armamentarium of a dermatologist by proposing a novel way to characterize AK lesions,” the researchers wrote.

The study findings were limited by several factors including the inability to confirm which AKs would transform into SCCs based on color, and the inclusion of a study population with advanced AKs that may not generalize to typical AKs, the researchers noted. More research is needed to explore the impact of AK color on SCC development, they emphasized.

However, the results represent a novel way to characterize AK lesions, and triage them in a way that may spare some patients from unneeded biopsies, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.

“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.

“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.

While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.

“A 40% increased risk of diabetes is a big surprise,” he said in an interview.

“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
 

U-shaped relationship between levothyroxine dose and diabetes risk

The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.

The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m².

Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.

The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).

In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).

A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).

“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.

However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.

“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
 

Potential mechanisms

Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.

The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.

Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.

Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values. 

“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
 

Control group should have had hypothyroidism

The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.

“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.

In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.

“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.

“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”

Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.

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

People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.

“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.

“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.

While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.

“A 40% increased risk of diabetes is a big surprise,” he said in an interview.

“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
 

U-shaped relationship between levothyroxine dose and diabetes risk

The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.

The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m².

Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.

The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).

In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).

A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).

“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.

However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.

“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
 

Potential mechanisms

Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.

The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.

Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.

Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values. 

“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
 

Control group should have had hypothyroidism

The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.

“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.

In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.

“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.

“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”

Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.

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

People with thyroid cancer treated with thyroidectomy have as much as a 40% increased risk of developing type 2 diabetes, regardless of their age, with the elevated risk observed with low as well as high doses of postoperative levothyroxine, new research shows.

“This is the first population-based study to demonstrate an elevated risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer, compared with that in matched controls,” wrote the authors of the research, published recently in the Journal of Clinical Endocrinology & Metabolism.

“Notably, there was a U-shaped relationship between postoperative levothyroxine dosage, a surrogate marker of TSH suppression, and the risk of type 2 diabetes,” said Hye Jin Yoo, MD, of the division of endocrinology and metabolism, Korea University College of Medicine, Seoul, and colleagues.

While other studies have linked thyroidectomy for thyroid cancer with an elevated risk for other metabolic conditions, including coronary heart disease and ischemic stroke, the relatively high diabetes risk is unexpected, said Tyler Drake, MD, an endocrinologist with the Minneapolis VA Health Care System.

“A 40% increased risk of diabetes is a big surprise,” he said in an interview.

“Diabetes is very common, with about one in 10 U.S. adults having type 2 diabetes, but a 40% increased risk in thyroid cancer patients is higher than I see in my clinical practice. [However], it is important to note that the [highest] risk was predominantly among the groups on the lowest and highest doses of levothyroxine,” said Dr. Drake, assistant professor of medicine at the University of Minnesota, Minneapolis.
 

U-shaped relationship between levothyroxine dose and diabetes risk

The findings are from a study of 36,377 patients with thyroid cancer in the National Health Insurance Service (NHIS) database in Korea who had undergone a thyroidectomy between 2004 and 2013.

The patients were matched 1:1 with controls who had nonthyroid cancers. Their mean age was 46.6 years, about 30% were male, and their mean body mass index was 23.8 kg/m².

Over a mean follow-up of 6.6 years, the patients with thyroid cancer had a significantly higher risk of developing type 2 diabetes, at a rate of 47.5% (10,812) compared with 36.9% (9414; HR, 1.43; P < .001) in the control group, after adjustment for factors such as age, sex, BMI, smoking, drinking, systolic blood pressure, and fasting glucose.

The risk of type 2 diabetes among those with thyroid cancer was higher among the 83.2% of patients who underwent a total thyroidectomy compared with the 16.8% who had a unilateral lobectomy (HR, 1.06; P < .001).

In addition, those with thyroid cancer who received the lowest as well as highest dosages of levothyroxine had significantly higher risks of type 2 diabetes compared with controls (HR, 1.50 and 1.39, respectively; both P < .001).

A closer look at quartiles of levothyroxine dosing showed the first (lowest) quartile (defined as a mean levothyroxine dosage of < 101 mcg/day) was associated with an increased risk of type 2 diabetes compared with the second quartile group (101-127 mcg/day; HR, 1.45), as was the fourth quartile (≥ 150 mcg/day; HR, 1.37), while a decreased risk of type 2 diabetes was observed in the third quartile group (128-149 mcg/day versus the second quartile group; HR, 0.91).

“This result suggests a U-shaped relationship between the mean levothyroxine dosage and risk of type 2 diabetes in postthyroidectomy patients with thyroid cancer,” the authors said.

However, “consistent with previous studies, the present study showed that the highest risk of type 2 diabetes was observed in patients with thyroid cancer who were treated with the lowest mean dosage of levothyroxine,” they noted.

“This result suggests that inadequate supplementation of thyroid hormones may worsen glucose metabolism and should therefore be avoided.”
 

Potential mechanisms

Abnormal thyroid function, including hypo- and hyperthyroidism, following thyroidectomy and subsequent treatment with levothyroxine, is known to have potentially detrimental effects on glucose regulation among patients with thyroid cancer.

The potential mechanisms linking hypothyroidism with diabetes specifically include the possibility that insulin becomes unable to promote the utilization of glucose by muscles and adipose tissue. However, thyroid hormone replacement has been associated with a normalization of insulin sensitivity, the authors noted.

Meanwhile, glucose intolerance is common among patients with hyperthyroidism, largely due to an increase in hepatic glucose production, and likewise, the normalization of thyroid levels among those treated with methimazole has been linked to normalization of glucose and lipid metabolism alterations.

Dr. Drake noted that an important study limitation is that patients were analyzed based on their levothyroxine dose and not their TSH values, which the authors explain was due to the unavailability of the TSH values. 

“By looking at levothyroxine doses, and not TSH values, it is possible some patients were being improperly treated with either too much or too little levothyroxine,” Dr. Drake noted.
 

Control group should have had hypothyroidism

The findings nevertheless shed light on the risk of diabetes following thyroidectomy for thyroid cancer, Anupam Kotwal, MD, commented on the study.

“This study is significant because it addresses an important topic exploring the link between thyroid dysfunction and metabolic disease, in this case ... hypothyroidism, due to surgery for thyroid cancer and type 2 diabetes,” Dr. Kotwal, assistant professor of medicine in the division of diabetes, endocrinology & metabolism at the University of Nebraska Medical Center, Omaha, said in an interview.

In terms of other limitations, Dr. Kotwal noted that the controls did not have hypothyroidism; therefore, “from this study, it is impossible to confirm whether hypothyroidism from any cause would be associated with higher incidence of diabetes or if it is specific to thyroid surgery for thyroid cancer.

“It would have been useful to have a control group of autoimmune primary hypothyroidism to evaluate the rate of diabetes during a similar follow-up duration,” Dr. Kotwal said.

“Hence, cohort studies with more granular data such as degree of TSH suppression and having a control group of hypothyroid patients due to autoimmune thyroid disease are needed to better understand this risk.”

Dr. Kotwal and Dr. Drake have reported no relevant financial relationships.

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

Interruption of 4-6 cyclin D-dependent kinase inhibitors (CDK4/6i) was associated with a high rate of progression among women with metastatic breast cancer, particularly those with liver metastases. The treatment interruptions occurred during the COVID-19 pandemic, out of concern that myelosuppression from the drugs might make patients more vulnerable to COVID-19 infection, and that other side effects might be confused with symptoms of COVID-19 infection.

The finding comes from a multicenter study presented by Sophie Martin, PhD, at the San Antonio Breast Cancer Symposium. Dr. Martin is a researcher at ICANS Institut de cancérologie Strasbourg Europe. The patient population had a complete or partial response, or stable disease complete for at least 6 months.

Although CDK4/6i combined with endocrine therapy has led to significant improvements in outcomes among metastatic HR-positive, HER-2-negative patients, the treatment can lead to chronic toxicities that may affect quality of life.

In its 2020 guidance on management of cancer patients during the COVID-19 pandemic, the European Society for Medical Oncology noted that cancer patients are at higher risk of severe symptoms and worse outcomes. However, it points out that there is no direct evidence that neutropenia caused CDK4/6i or poly-adenosine diphosphate ribose polymer inhibitors leads to an increase risk of COVID-19 infection.

The American Society for Clinical Oncology guidance for managing treatment of cancer patients in the context of COVID-19 also says there is little direct evidence to guide practice regarding therapies that may lead to immunosuppression. Therefore, the society recommends against changing or withholding those drugs. “The balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection is very uncertain,” the authors wrote.

There were 60 patients in the study, and the median age was 64 years. The average interruption period was 8 weeks. Twenty-two patients (37%) experienced radiological and/or clinical disease progression. Sixteen of the 22 (73%) restarted on CDK4/6I, while the remaining 4 patients initiated chemotherapy or targeted therapy. Two patients died during CDK4/6i treatment interruption. A univariate analysis found that the presence of liver metastases was associated with increased risk of progression during CDK4/6I withdrawal (odds ratio, 5.50; 95% confidence interval, 1.14-26.41).

There was also a trend toward greater likelihood of disease progression when the withdrawal period was 2 or more months (OR, 2.38), but the finding was not statistically significant. Although the study looked at treatment interruption due to the COVID-19 pandemic, the authors noted that the findings likely apply to other reasons for interruption, such as analgesic radiotherapy or programmed surgery.

Although the study authors advise against stopping CDK4/6i inhibitors, another small study conducted at a single German center suggested that treatment interruption might be an option in patients with stable disease. The authors examined elective CDK4/6i discontinuation among 22 patients with advanced, hormone receptor–positive, HER-2-negative breast cancer who had stable disease for at least 6 months with treatment regimens of CDK4/6i plus aromatase inhibitors or fulvestrant. After discontinuation of CDK4/6i but maintenance of endocrine therapy, 13 patients had stable disease, 8 had a partial response, and 1 had a complete response. After withdrawal, 5 patients had a local relapse and 1 experienced systemic progression. The patients restabilized with chemotherapy or retreatment with CDK4/6i.

“Discontinuation of CDK4/6 inhibitors seems to be safe in selected patients with metastatic HR-positive HER-2-negative breast cancer and prolonged disease control,” the authors wrote, although they noted that the results need to be backed up with prospective clinical trials.

Both studies had small sample sizes and were retrospective in nature.

One author on the COVID-19 study has received consulting fees from Lilly, Novartis, Pfizer, Daïchi, Seagen, and AstraZeneca. Authors of the German study have received honoraria from Iomedico, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, and BMS.

Interruption of 4-6 cyclin D-dependent kinase inhibitors (CDK4/6i) was associated with a high rate of progression among women with metastatic breast cancer, particularly those with liver metastases. The treatment interruptions occurred during the COVID-19 pandemic, out of concern that myelosuppression from the drugs might make patients more vulnerable to COVID-19 infection, and that other side effects might be confused with symptoms of COVID-19 infection.

The finding comes from a multicenter study presented by Sophie Martin, PhD, at the San Antonio Breast Cancer Symposium. Dr. Martin is a researcher at ICANS Institut de cancérologie Strasbourg Europe. The patient population had a complete or partial response, or stable disease complete for at least 6 months.

Although CDK4/6i combined with endocrine therapy has led to significant improvements in outcomes among metastatic HR-positive, HER-2-negative patients, the treatment can lead to chronic toxicities that may affect quality of life.

In its 2020 guidance on management of cancer patients during the COVID-19 pandemic, the European Society for Medical Oncology noted that cancer patients are at higher risk of severe symptoms and worse outcomes. However, it points out that there is no direct evidence that neutropenia caused CDK4/6i or poly-adenosine diphosphate ribose polymer inhibitors leads to an increase risk of COVID-19 infection.

The American Society for Clinical Oncology guidance for managing treatment of cancer patients in the context of COVID-19 also says there is little direct evidence to guide practice regarding therapies that may lead to immunosuppression. Therefore, the society recommends against changing or withholding those drugs. “The balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection is very uncertain,” the authors wrote.

There were 60 patients in the study, and the median age was 64 years. The average interruption period was 8 weeks. Twenty-two patients (37%) experienced radiological and/or clinical disease progression. Sixteen of the 22 (73%) restarted on CDK4/6I, while the remaining 4 patients initiated chemotherapy or targeted therapy. Two patients died during CDK4/6i treatment interruption. A univariate analysis found that the presence of liver metastases was associated with increased risk of progression during CDK4/6I withdrawal (odds ratio, 5.50; 95% confidence interval, 1.14-26.41).

There was also a trend toward greater likelihood of disease progression when the withdrawal period was 2 or more months (OR, 2.38), but the finding was not statistically significant. Although the study looked at treatment interruption due to the COVID-19 pandemic, the authors noted that the findings likely apply to other reasons for interruption, such as analgesic radiotherapy or programmed surgery.

Although the study authors advise against stopping CDK4/6i inhibitors, another small study conducted at a single German center suggested that treatment interruption might be an option in patients with stable disease. The authors examined elective CDK4/6i discontinuation among 22 patients with advanced, hormone receptor–positive, HER-2-negative breast cancer who had stable disease for at least 6 months with treatment regimens of CDK4/6i plus aromatase inhibitors or fulvestrant. After discontinuation of CDK4/6i but maintenance of endocrine therapy, 13 patients had stable disease, 8 had a partial response, and 1 had a complete response. After withdrawal, 5 patients had a local relapse and 1 experienced systemic progression. The patients restabilized with chemotherapy or retreatment with CDK4/6i.

“Discontinuation of CDK4/6 inhibitors seems to be safe in selected patients with metastatic HR-positive HER-2-negative breast cancer and prolonged disease control,” the authors wrote, although they noted that the results need to be backed up with prospective clinical trials.

Both studies had small sample sizes and were retrospective in nature.

One author on the COVID-19 study has received consulting fees from Lilly, Novartis, Pfizer, Daïchi, Seagen, and AstraZeneca. Authors of the German study have received honoraria from Iomedico, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, and BMS.

Interruption of 4-6 cyclin D-dependent kinase inhibitors (CDK4/6i) was associated with a high rate of progression among women with metastatic breast cancer, particularly those with liver metastases. The treatment interruptions occurred during the COVID-19 pandemic, out of concern that myelosuppression from the drugs might make patients more vulnerable to COVID-19 infection, and that other side effects might be confused with symptoms of COVID-19 infection.

The finding comes from a multicenter study presented by Sophie Martin, PhD, at the San Antonio Breast Cancer Symposium. Dr. Martin is a researcher at ICANS Institut de cancérologie Strasbourg Europe. The patient population had a complete or partial response, or stable disease complete for at least 6 months.

Although CDK4/6i combined with endocrine therapy has led to significant improvements in outcomes among metastatic HR-positive, HER-2-negative patients, the treatment can lead to chronic toxicities that may affect quality of life.

In its 2020 guidance on management of cancer patients during the COVID-19 pandemic, the European Society for Medical Oncology noted that cancer patients are at higher risk of severe symptoms and worse outcomes. However, it points out that there is no direct evidence that neutropenia caused CDK4/6i or poly-adenosine diphosphate ribose polymer inhibitors leads to an increase risk of COVID-19 infection.

The American Society for Clinical Oncology guidance for managing treatment of cancer patients in the context of COVID-19 also says there is little direct evidence to guide practice regarding therapies that may lead to immunosuppression. Therefore, the society recommends against changing or withholding those drugs. “The balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection is very uncertain,” the authors wrote.

There were 60 patients in the study, and the median age was 64 years. The average interruption period was 8 weeks. Twenty-two patients (37%) experienced radiological and/or clinical disease progression. Sixteen of the 22 (73%) restarted on CDK4/6I, while the remaining 4 patients initiated chemotherapy or targeted therapy. Two patients died during CDK4/6i treatment interruption. A univariate analysis found that the presence of liver metastases was associated with increased risk of progression during CDK4/6I withdrawal (odds ratio, 5.50; 95% confidence interval, 1.14-26.41).

There was also a trend toward greater likelihood of disease progression when the withdrawal period was 2 or more months (OR, 2.38), but the finding was not statistically significant. Although the study looked at treatment interruption due to the COVID-19 pandemic, the authors noted that the findings likely apply to other reasons for interruption, such as analgesic radiotherapy or programmed surgery.

Although the study authors advise against stopping CDK4/6i inhibitors, another small study conducted at a single German center suggested that treatment interruption might be an option in patients with stable disease. The authors examined elective CDK4/6i discontinuation among 22 patients with advanced, hormone receptor–positive, HER-2-negative breast cancer who had stable disease for at least 6 months with treatment regimens of CDK4/6i plus aromatase inhibitors or fulvestrant. After discontinuation of CDK4/6i but maintenance of endocrine therapy, 13 patients had stable disease, 8 had a partial response, and 1 had a complete response. After withdrawal, 5 patients had a local relapse and 1 experienced systemic progression. The patients restabilized with chemotherapy or retreatment with CDK4/6i.

“Discontinuation of CDK4/6 inhibitors seems to be safe in selected patients with metastatic HR-positive HER-2-negative breast cancer and prolonged disease control,” the authors wrote, although they noted that the results need to be backed up with prospective clinical trials.

Both studies had small sample sizes and were retrospective in nature.

One author on the COVID-19 study has received consulting fees from Lilly, Novartis, Pfizer, Daïchi, Seagen, and AstraZeneca. Authors of the German study have received honoraria from Iomedico, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, and BMS.

As compared with standard of care, an investigational oral selective estrogen receptor degrader (SERD) demonstrated a 30% lower risk of death or disease progression in women with estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Findings from the phase 3 EMERALD trial, presented at the San Antonio Breast Cancer Symposium, revealed that the effects of elacestrant (Menarini and Radius Health) were even more pronounced in women with ESR1 mutations. Women in the elacestrant arm had a 45% reduced risk of death or disease progression in comparison with those who received standard of care.

This new agent is the “first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second- and third-line settings,” said lead author Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center and associate professor at Harvard Medical School, both in Boston. “Clinically, elacestrant has the potential to become the new standard of care in the study population.”

Endocrine therapy and CDK4/6 inhibitors remain the mainstay for the management of ER-positive/HER2 metastatic breast cancer. However, most patients will eventually develop resistance to these agents, often caused by the development of ESR1 mutations.

At the current time, fulvestrant is the only SERD available on the U.S. market, which means there is an urgent unmet need for new, effective SERDs in this setting, especially for patients harboring ESR1 mutations, Dr. Bardia explained.

In an early phase 1 trial, Dr. Bardia and his team evaluated elacestrant for safety and antitumor activity and found it had an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with ER-positive metastatic breast cancer.

This trial provided the rationale for investigating elacestrant in a phase 3 setting, Dr. Bardia said.

The multicenter, randomized, controlled phase 3 EMERALD trial included 477 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer who had received one or two prior lines of endocrine therapy and no more than one line of chemotherapy in the metastatic setting. Patients had also progressed on prior treatment with a CDK4/6 inhibitor.

Patients were randomized to elacestrant 400 mg orally daily (n = 239) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor, n = 238). The cohorts were further stratified by ESR1 mutation status, prior fulvestrant exposure, and presence of visceral disease.

The coprimary endpoints were progression-free survival in patients with tumors harboring ESR1 mutations and in the entire cohort. Secondary endpoints included overall survival, safety, tolerability, and quality of life.

“This was a positive study as it met both primary endpoints,” said Dr. Bardia.

The team found a 30% reduction in the risk of progression or death in the elacestrant arm for all patients (hazard ratio, 0.697; P = .0018) and a 45% (HR, 0.546; P =.0005) reduction in the risk of progression or death among those with ESR1 mutations.

At 12 months, the progression-free survival rate was 22.32% with elacestrant versus 9.42% for those receiving the standard of care. Among the ESR1 mutation group, those rates were slightly more pronounced: 26.76% with elacestrant versus 8.19% with standard of care.

Overall survival data were not yet mature but trended in favor of elacestrant in all patients (HR, 0.751; P = .0821) as well as those with ESR1 mutations (HR, 0.592; P = .0325). The final overall survival analysis is expected next year, Dr. Bardia said.

Common treatment-related adverse events with elacestrant versus standard of care included mostly grade 1 or 2 nausea (25.3% vs. 8.7%), vomiting (11% vs. 2.6%), and fatigue (11% vs. 7.9%). The rate of grade 3 or higher adverse events was 7.2% in the elacestrant arm versus 3.1% in the standard of care group and was mainly driven by nausea. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% and 4.4%, respectively). No treatment-related deaths occurred in either group.

Dr. Bardia added that further studies are planned and assess the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies, such as CDK4/6 inhibitors.

Weighing in on the recent findings, Carlos Arteaga, MD, who was not involved in the research, said this represents an important study evaluating a therapeutic priority.

“The data suggest that [elacestrant] may be a new option, not only as monotherapy but in combination with other therapies,” Dr. Arteaga, director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, and cochair of SABCS, said in an interview.

Coral Omene, MD, PhD, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, both in New Brunswick, also commented on the importance of the EMERALD results.

“I would think that this is practice changing,” said Dr. Omene, who was also not involved in the research. The new oral SERD “demonstrates a significant advantage in progression-free survival over either fulvestrant or an aromatase inhibitor.”

An oral drug could also potentially save patients from painful injections that can occasionally result in injection-site abscesses from long-term administration, she explained. “It’s also more convenient to take oral pills at home. It saves on transportation and omits waiting in treatment rooms for administrations.”

Although the overall survival data are not yet mature and the rate of adverse events was higher with elacestrant, “progression-free survival is a surrogate endpoint widely used for overall survival and is reasonable to consider a treatment regimen based on this while awaiting mature survival data,” Dr. Omene added. “The increase in nausea and vomiting seen in oral SERD arm is likely manageable, as there were no significant differences in discontinuation in both arms of treatment.”

The study was supported by Radius Health. Dr. Bardia has served as a consultant or on an advisory board for Radius Health, Pfizer, Novartis, Genentech, Merck, Immunomedics/Gilead, Sanofi, Daiichi Sankyo/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. He has conducted contracted research or received grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Sankyo/AstraZeneca, Natera, and Eli Lilly.

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

As compared with standard of care, an investigational oral selective estrogen receptor degrader (SERD) demonstrated a 30% lower risk of death or disease progression in women with estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Findings from the phase 3 EMERALD trial, presented at the San Antonio Breast Cancer Symposium, revealed that the effects of elacestrant (Menarini and Radius Health) were even more pronounced in women with ESR1 mutations. Women in the elacestrant arm had a 45% reduced risk of death or disease progression in comparison with those who received standard of care.

This new agent is the “first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second- and third-line settings,” said lead author Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center and associate professor at Harvard Medical School, both in Boston. “Clinically, elacestrant has the potential to become the new standard of care in the study population.”

Endocrine therapy and CDK4/6 inhibitors remain the mainstay for the management of ER-positive/HER2 metastatic breast cancer. However, most patients will eventually develop resistance to these agents, often caused by the development of ESR1 mutations.

At the current time, fulvestrant is the only SERD available on the U.S. market, which means there is an urgent unmet need for new, effective SERDs in this setting, especially for patients harboring ESR1 mutations, Dr. Bardia explained.

In an early phase 1 trial, Dr. Bardia and his team evaluated elacestrant for safety and antitumor activity and found it had an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with ER-positive metastatic breast cancer.

This trial provided the rationale for investigating elacestrant in a phase 3 setting, Dr. Bardia said.

The multicenter, randomized, controlled phase 3 EMERALD trial included 477 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer who had received one or two prior lines of endocrine therapy and no more than one line of chemotherapy in the metastatic setting. Patients had also progressed on prior treatment with a CDK4/6 inhibitor.

Patients were randomized to elacestrant 400 mg orally daily (n = 239) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor, n = 238). The cohorts were further stratified by ESR1 mutation status, prior fulvestrant exposure, and presence of visceral disease.

The coprimary endpoints were progression-free survival in patients with tumors harboring ESR1 mutations and in the entire cohort. Secondary endpoints included overall survival, safety, tolerability, and quality of life.

“This was a positive study as it met both primary endpoints,” said Dr. Bardia.

The team found a 30% reduction in the risk of progression or death in the elacestrant arm for all patients (hazard ratio, 0.697; P = .0018) and a 45% (HR, 0.546; P =.0005) reduction in the risk of progression or death among those with ESR1 mutations.

At 12 months, the progression-free survival rate was 22.32% with elacestrant versus 9.42% for those receiving the standard of care. Among the ESR1 mutation group, those rates were slightly more pronounced: 26.76% with elacestrant versus 8.19% with standard of care.

Overall survival data were not yet mature but trended in favor of elacestrant in all patients (HR, 0.751; P = .0821) as well as those with ESR1 mutations (HR, 0.592; P = .0325). The final overall survival analysis is expected next year, Dr. Bardia said.

Common treatment-related adverse events with elacestrant versus standard of care included mostly grade 1 or 2 nausea (25.3% vs. 8.7%), vomiting (11% vs. 2.6%), and fatigue (11% vs. 7.9%). The rate of grade 3 or higher adverse events was 7.2% in the elacestrant arm versus 3.1% in the standard of care group and was mainly driven by nausea. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% and 4.4%, respectively). No treatment-related deaths occurred in either group.

Dr. Bardia added that further studies are planned and assess the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies, such as CDK4/6 inhibitors.

Weighing in on the recent findings, Carlos Arteaga, MD, who was not involved in the research, said this represents an important study evaluating a therapeutic priority.

“The data suggest that [elacestrant] may be a new option, not only as monotherapy but in combination with other therapies,” Dr. Arteaga, director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, and cochair of SABCS, said in an interview.

Coral Omene, MD, PhD, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, both in New Brunswick, also commented on the importance of the EMERALD results.

“I would think that this is practice changing,” said Dr. Omene, who was also not involved in the research. The new oral SERD “demonstrates a significant advantage in progression-free survival over either fulvestrant or an aromatase inhibitor.”

An oral drug could also potentially save patients from painful injections that can occasionally result in injection-site abscesses from long-term administration, she explained. “It’s also more convenient to take oral pills at home. It saves on transportation and omits waiting in treatment rooms for administrations.”

Although the overall survival data are not yet mature and the rate of adverse events was higher with elacestrant, “progression-free survival is a surrogate endpoint widely used for overall survival and is reasonable to consider a treatment regimen based on this while awaiting mature survival data,” Dr. Omene added. “The increase in nausea and vomiting seen in oral SERD arm is likely manageable, as there were no significant differences in discontinuation in both arms of treatment.”

The study was supported by Radius Health. Dr. Bardia has served as a consultant or on an advisory board for Radius Health, Pfizer, Novartis, Genentech, Merck, Immunomedics/Gilead, Sanofi, Daiichi Sankyo/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. He has conducted contracted research or received grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Sankyo/AstraZeneca, Natera, and Eli Lilly.

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

As compared with standard of care, an investigational oral selective estrogen receptor degrader (SERD) demonstrated a 30% lower risk of death or disease progression in women with estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

Findings from the phase 3 EMERALD trial, presented at the San Antonio Breast Cancer Symposium, revealed that the effects of elacestrant (Menarini and Radius Health) were even more pronounced in women with ESR1 mutations. Women in the elacestrant arm had a 45% reduced risk of death or disease progression in comparison with those who received standard of care.

This new agent is the “first oral SERD to demonstrate a statistically significant and clinically meaningful improvement of progression-free survival in patients with ER-positive/HER2-negative metastatic breast cancer in the second- and third-line settings,” said lead author Aditya Bardia, MD, MPH, director of the breast cancer research program at Mass General Cancer Center and associate professor at Harvard Medical School, both in Boston. “Clinically, elacestrant has the potential to become the new standard of care in the study population.”

Endocrine therapy and CDK4/6 inhibitors remain the mainstay for the management of ER-positive/HER2 metastatic breast cancer. However, most patients will eventually develop resistance to these agents, often caused by the development of ESR1 mutations.

At the current time, fulvestrant is the only SERD available on the U.S. market, which means there is an urgent unmet need for new, effective SERDs in this setting, especially for patients harboring ESR1 mutations, Dr. Bardia explained.

In an early phase 1 trial, Dr. Bardia and his team evaluated elacestrant for safety and antitumor activity and found it had an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with ER-positive metastatic breast cancer.

This trial provided the rationale for investigating elacestrant in a phase 3 setting, Dr. Bardia said.

The multicenter, randomized, controlled phase 3 EMERALD trial included 477 postmenopausal women with ER-positive/HER2-negative metastatic breast cancer who had received one or two prior lines of endocrine therapy and no more than one line of chemotherapy in the metastatic setting. Patients had also progressed on prior treatment with a CDK4/6 inhibitor.

Patients were randomized to elacestrant 400 mg orally daily (n = 239) or standard of care (investigator’s choice of fulvestrant or an aromatase inhibitor, n = 238). The cohorts were further stratified by ESR1 mutation status, prior fulvestrant exposure, and presence of visceral disease.

The coprimary endpoints were progression-free survival in patients with tumors harboring ESR1 mutations and in the entire cohort. Secondary endpoints included overall survival, safety, tolerability, and quality of life.

“This was a positive study as it met both primary endpoints,” said Dr. Bardia.

The team found a 30% reduction in the risk of progression or death in the elacestrant arm for all patients (hazard ratio, 0.697; P = .0018) and a 45% (HR, 0.546; P =.0005) reduction in the risk of progression or death among those with ESR1 mutations.

At 12 months, the progression-free survival rate was 22.32% with elacestrant versus 9.42% for those receiving the standard of care. Among the ESR1 mutation group, those rates were slightly more pronounced: 26.76% with elacestrant versus 8.19% with standard of care.

Overall survival data were not yet mature but trended in favor of elacestrant in all patients (HR, 0.751; P = .0821) as well as those with ESR1 mutations (HR, 0.592; P = .0325). The final overall survival analysis is expected next year, Dr. Bardia said.

Common treatment-related adverse events with elacestrant versus standard of care included mostly grade 1 or 2 nausea (25.3% vs. 8.7%), vomiting (11% vs. 2.6%), and fatigue (11% vs. 7.9%). The rate of grade 3 or higher adverse events was 7.2% in the elacestrant arm versus 3.1% in the standard of care group and was mainly driven by nausea. Treatment-emergent adverse events leading to discontinuation of elacestrant or standard of care were infrequent in both arms (6.3% and 4.4%, respectively). No treatment-related deaths occurred in either group.

Dr. Bardia added that further studies are planned and assess the efficacy of elacestrant during earlier lines of treatment and in combination with other therapies, such as CDK4/6 inhibitors.

Weighing in on the recent findings, Carlos Arteaga, MD, who was not involved in the research, said this represents an important study evaluating a therapeutic priority.

“The data suggest that [elacestrant] may be a new option, not only as monotherapy but in combination with other therapies,” Dr. Arteaga, director of Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, and cochair of SABCS, said in an interview.

Coral Omene, MD, PhD, a medical oncologist at Rutgers Cancer Institute of New Jersey and assistant professor of medicine at Robert Wood Johnson Medical School, both in New Brunswick, also commented on the importance of the EMERALD results.

“I would think that this is practice changing,” said Dr. Omene, who was also not involved in the research. The new oral SERD “demonstrates a significant advantage in progression-free survival over either fulvestrant or an aromatase inhibitor.”

An oral drug could also potentially save patients from painful injections that can occasionally result in injection-site abscesses from long-term administration, she explained. “It’s also more convenient to take oral pills at home. It saves on transportation and omits waiting in treatment rooms for administrations.”

Although the overall survival data are not yet mature and the rate of adverse events was higher with elacestrant, “progression-free survival is a surrogate endpoint widely used for overall survival and is reasonable to consider a treatment regimen based on this while awaiting mature survival data,” Dr. Omene added. “The increase in nausea and vomiting seen in oral SERD arm is likely manageable, as there were no significant differences in discontinuation in both arms of treatment.”

The study was supported by Radius Health. Dr. Bardia has served as a consultant or on an advisory board for Radius Health, Pfizer, Novartis, Genentech, Merck, Immunomedics/Gilead, Sanofi, Daiichi Sankyo/AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. He has conducted contracted research or received grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Sankyo/AstraZeneca, Natera, and Eli Lilly.

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

Blood pressure control declined in both men and women with the onset of the COVID-19 pandemic in the United States in 2020, especially among women and older adults, according to a new analysis.

Ingram Publishing/ThinkStock

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

Blood pressure control declined in both men and women with the onset of the COVID-19 pandemic in the United States in 2020, especially among women and older adults, according to a new analysis.

Ingram Publishing/ThinkStock

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

Blood pressure control declined in both men and women with the onset of the COVID-19 pandemic in the United States in 2020, especially among women and older adults, according to a new analysis.

Ingram Publishing/ThinkStock

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

In 2011, the Mayo Clinic began surveying physicians about burnout and found 45% of physicians experienced at least one symptom, such as emotional exhaustion, finding work no longer meaningful, feelings of ineffectiveness, and depersonalizing patients. Associated manifestations can range from headache and insomnia to impaired memory and decreased attention. 

Marija Jovovic/Getty Images

Fast forward 10 years to the Medscape National Physician Burnout and Suicide Report, which found that a similar number of physicians (42%) feel burned out. The COVID-19 pandemic only added insult to injury. A Medscape survey that included nearly 5,000 U.S. physicians revealed that about two-thirds (64%) of them reported burnout had intensified during the crisis.

These elevated numbers are being labeled as “a public health crisis” for the impact widespread physician burnout could have on the health of the doctor and patient safety. The relatively consistent levels across the decade seem to suggest that, if health organizations are attempting to improve physician well-being, it doesn’t appear to be working, forcing doctors to find solutions for themselves.

Jill Wener, MD, considers herself part of the 45% burned out 10 years ago. She was working as an internist at Rush University Medical Center in Chicago, but the “existential reality of being a doctor in this world” was wearing on her. “Staying up with the literature, knowing that every day you’re going to go into work without knowing what you’re going to find, threats of lawsuits, the pressure of perfectionism,” Dr. Wener told this news organization. “By the time I hit burnout, everything made me feel like the world was crashing down on me.”

When Dr. Wener encountered someone who meditated twice a day, she was intrigued, even though the self-described “most Type-A, inside-the-box, nonspiritual type, anxious, linear-path doctor” didn’t think people like her could meditate. Dr. Wener is not alone in her hesitation to explore meditation as a means to help prevent burnout because the causes of burnout are primarily linked to external rather than internal factors. Issues including a loss of autonomy, the burden and distraction of electronic health records, and the intense pressure to comply with rules from the government are not things mindfulness can fix. 

And because the sources of burnout are primarily environmental and inherent to the current medical system, the suggestion that physicians need to fix themselves with meditation can come as a slap in the face. However, when up against a system slow to change, mindfulness can provide physicians access to the one thing they can control: How they perceive and react to what’s in front of them.

At the recommendation of an acquaintance, Dr. Wener enrolled in a Vedic Meditation (also known as Conscious Health Meditation) course taught by Light Watkins, a well-known traveling instructor, author, and speaker. By the second meeting she was successfully practicing 20 minutes twice a day. This form of mediation traces its roots to the Vedas, ancient Indian texts (also the foundation for yoga), and uses a mantra to settle the mind, transitioning to an awake state of inner contentment. 

Three weeks later, Dr. Wener’s daily crying jags ended as did her propensity for road rage. “I felt like I was on the cusp of something life-changing, I just didn’t understand it,” she recalled. “But I knew I was never going to give it up.”
 

Defining mindfulness

“Mindfulness is being able to be present in the moment that you’re in with acceptance of what it is and without judging it,” said Donna Rockwell, PsyD, a leading mindfulness meditation teacher. The practice of mindfulness is really meditation. Dr. Rockwell explained that the noise of our mind is most often focused on either the past or the future. “We’re either bemoaning something that happened earlier or we’re catastrophizing the future,” she said, which prevents us from being present in the moment. 

Meditation allows you to notice when your mind has drifted from the present moment into the past or future. “You gently notice it, label it with a lot of self-compassion, and then bring your mind back by focusing on your breath – going out, going in – and the incoming stimuli through your five senses,” said Dr. Rockwell. “When you’re doing that, you can’t be in the past or future.”

Dr. Rockwell also pointed out that we constantly categorize incoming data of the moment as either “good for me or bad for me,” which gets in the way of simply being present for what you’re facing. “When you’re more fully present, you become more skillful and able to do what this moment is asking of you,” she said. Being mindful allows us to better navigate incoming stimuli, which could be a “code blue” in the ED or a patient who needs another 2 minutes during an office visit. 

When Dr. Wener was burned out, she felt unable to adapt whenever something unexpected happened. “When you have no emotional reserves, everything feels like a big deal,” she said. “The meditation gave me what we call adaptation energy; it filled up my tank and kept me from feeling like I was going to lose it at 10 o’clock in the morning.”

Dr. Rockwell explained burnout as an overactive fight or flight response activated by the amygdala. It starts pumping cortisol, our pupils dilate, and our pores open. The prefrontal cortex is offline when we’re experiencing this physiological response because they both can’t be operational at the same time. “When we’re constantly in a ‘fight or flight’ response and don’t have any access to our prefrontal cortex, we are coming from a brain that is pumping cortisol and that leads to burnout,” said Dr. Rockwell.

“Any fight or flight response leaves a mark on your body,” Dr. Wener echoed. “When we go into our state of deep rest in the meditation practice, which is two to five times more restful than sleep, it heals those stress scars.”
 

Making time for mindfulness

Prescribing mindfulness for physicians is not new. Molecular biologist Jon Kabat-Zinn, PhD, developed Mindfulness-Based Stress Reduction (MBSR) in 1979, a practice that incorporates mindfulness exercises to help people become familiar with their behavior patterns in stressful situations. Thus, instead of reacting, they can respond with a clearer understanding of the circumstance. Dr. Kabat-Zinn initially targeted people with chronic health problems to help them cope with the effects of pain and the condition of their illness, but it has expanded to anyone experiencing challenges in their life, including physicians. A standard MBSR course runs 8 weeks, making it a commitment for most people. 

Mindfulness training requires that physicians use what they already have so little of: time.

Dr. Wener was able to take a sabbatical, embarking on a 3-month trip to India to immerse herself in the study of Vedic Meditation. Upon her return, Dr. Wener took a position at Emory University, Atlanta, and has launched a number of CME-accredited meditation courses and retreats. Unlike Dr. Kabat-Zinn, her programs are by physicians and for physicians. She also created an online version of the meditation course to make it more accessible. 

For these reasons, Kara Pepper, MD, an internist in outpatient primary care in Atlanta, was drawn to the meditation course. Dr. Pepper was 7 years into practice when she burned out. “The program dovetailed into my burnout recovery,” she said. “It allowed me space to separate myself from the thoughts I was having about work and just recognize them as just that – as thoughts.”

In the course, Dr. Wener teaches the REST Technique, which she says is different than mindfulness in that she encourages the mind to run rampant. “Trying to control the mind can feel very uncomfortable because we always have thoughts,” she says. “We can’t tell the mind to stop thinking just like we can’t tell the heart to stop beating.” Dr. Wener said the REST Technique lets “the mind swim downstream,” allowing the brain to go into a deep state of rest and start to heal from the scars caused by stress. 

Dr. Pepper said the self-paced online course gave her all the tools she needed, and it was pragmatic and evidence based. “I didn’t feel ‘woo’ or like another gimmick,” she said. Pepper, who continues to practice medicine, became a life coach in 2019 to teach others the skills she uses daily. 
 

An integrated strategy

Dr. Wener acknowledges that meditation is not the panacea for everyone’s burnout, which data support. In a review published in The American Journal of Medicine in 2019, Scott Yates, MD, MBA, from the Center for Executive Medicine in Plano, Tex., found that physicians who had adopted mediation and mindfulness training to decrease anxiety and perceived work stress only experienced modest benefits. In fact, Dr. Yates claims that there’s little data to suggest the long-term benefit of any particular stress management intervention in the prevention of burnout symptoms. 

“The often-repeated goals of the Triple Aim [enhancing patient experience, improving population health, and reducing costs] may be unreachable until we recognize and address burnout in health care providers,” Dr. Yates wrote. He recommends adding a fourth goal to specifically address physician wellness, which certainly could include mindfulness training and meditation.

Burnout coach, trainer, and consultant Dike Drummond, MD, also professes that physician wellness must be added as the key fourth ingredient to improving health care. “Burnout is a dilemma, a balancing act,” he said. “It takes an integrated strategy.” The CEO and founder of TheHappyMD.com, Dr. Drummond’s integrated strategy to stop physician burnout has been taught to more than 40,000 physicians in 175 organizations, and one element of that strategy can be mindfulness training. 

Dr. Drummond said he doesn’t use the word meditation “because that scares most people”; it takes a commitment and isn’t accessible for a lot of doctors. Instead, he coaches doctors to use a ‘single-breath’ technique to help them reset multiple times throughout the day. “I teach people how to breathe up to the top of their head and then down to the bottom of their feet,” Dr. Drummond said. He calls it the Squeegee Breath Technique because when they exhale, they “wipe away” anything that doesn’t need to be there right now. “If you happen to have a mindfulness practice like meditation, they work synergistically because the calmness you feel in your mediation is available to you at the bottom of these releasing breaths.”

Various studies and surveys provide great detail as to the “why” of physician burnout. And while mindfulness is not the sole answer, it’s something physicians can explore for themselves while health care as an industry looks for a more comprehensive solution. 

“It’s not rocket science,” Dr. Drummond insisted. “You want a different result? You’re not satisfied with the way things are now and you want to feel different? You absolutely must do something different.”

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

In 2011, the Mayo Clinic began surveying physicians about burnout and found 45% of physicians experienced at least one symptom, such as emotional exhaustion, finding work no longer meaningful, feelings of ineffectiveness, and depersonalizing patients. Associated manifestations can range from headache and insomnia to impaired memory and decreased attention. 

Marija Jovovic/Getty Images

Fast forward 10 years to the Medscape National Physician Burnout and Suicide Report, which found that a similar number of physicians (42%) feel burned out. The COVID-19 pandemic only added insult to injury. A Medscape survey that included nearly 5,000 U.S. physicians revealed that about two-thirds (64%) of them reported burnout had intensified during the crisis.

These elevated numbers are being labeled as “a public health crisis” for the impact widespread physician burnout could have on the health of the doctor and patient safety. The relatively consistent levels across the decade seem to suggest that, if health organizations are attempting to improve physician well-being, it doesn’t appear to be working, forcing doctors to find solutions for themselves.

Jill Wener, MD, considers herself part of the 45% burned out 10 years ago. She was working as an internist at Rush University Medical Center in Chicago, but the “existential reality of being a doctor in this world” was wearing on her. “Staying up with the literature, knowing that every day you’re going to go into work without knowing what you’re going to find, threats of lawsuits, the pressure of perfectionism,” Dr. Wener told this news organization. “By the time I hit burnout, everything made me feel like the world was crashing down on me.”

When Dr. Wener encountered someone who meditated twice a day, she was intrigued, even though the self-described “most Type-A, inside-the-box, nonspiritual type, anxious, linear-path doctor” didn’t think people like her could meditate. Dr. Wener is not alone in her hesitation to explore meditation as a means to help prevent burnout because the causes of burnout are primarily linked to external rather than internal factors. Issues including a loss of autonomy, the burden and distraction of electronic health records, and the intense pressure to comply with rules from the government are not things mindfulness can fix. 

And because the sources of burnout are primarily environmental and inherent to the current medical system, the suggestion that physicians need to fix themselves with meditation can come as a slap in the face. However, when up against a system slow to change, mindfulness can provide physicians access to the one thing they can control: How they perceive and react to what’s in front of them.

At the recommendation of an acquaintance, Dr. Wener enrolled in a Vedic Meditation (also known as Conscious Health Meditation) course taught by Light Watkins, a well-known traveling instructor, author, and speaker. By the second meeting she was successfully practicing 20 minutes twice a day. This form of mediation traces its roots to the Vedas, ancient Indian texts (also the foundation for yoga), and uses a mantra to settle the mind, transitioning to an awake state of inner contentment. 

Three weeks later, Dr. Wener’s daily crying jags ended as did her propensity for road rage. “I felt like I was on the cusp of something life-changing, I just didn’t understand it,” she recalled. “But I knew I was never going to give it up.”
 

Defining mindfulness

“Mindfulness is being able to be present in the moment that you’re in with acceptance of what it is and without judging it,” said Donna Rockwell, PsyD, a leading mindfulness meditation teacher. The practice of mindfulness is really meditation. Dr. Rockwell explained that the noise of our mind is most often focused on either the past or the future. “We’re either bemoaning something that happened earlier or we’re catastrophizing the future,” she said, which prevents us from being present in the moment. 

Meditation allows you to notice when your mind has drifted from the present moment into the past or future. “You gently notice it, label it with a lot of self-compassion, and then bring your mind back by focusing on your breath – going out, going in – and the incoming stimuli through your five senses,” said Dr. Rockwell. “When you’re doing that, you can’t be in the past or future.”

Dr. Rockwell also pointed out that we constantly categorize incoming data of the moment as either “good for me or bad for me,” which gets in the way of simply being present for what you’re facing. “When you’re more fully present, you become more skillful and able to do what this moment is asking of you,” she said. Being mindful allows us to better navigate incoming stimuli, which could be a “code blue” in the ED or a patient who needs another 2 minutes during an office visit. 

When Dr. Wener was burned out, she felt unable to adapt whenever something unexpected happened. “When you have no emotional reserves, everything feels like a big deal,” she said. “The meditation gave me what we call adaptation energy; it filled up my tank and kept me from feeling like I was going to lose it at 10 o’clock in the morning.”

Dr. Rockwell explained burnout as an overactive fight or flight response activated by the amygdala. It starts pumping cortisol, our pupils dilate, and our pores open. The prefrontal cortex is offline when we’re experiencing this physiological response because they both can’t be operational at the same time. “When we’re constantly in a ‘fight or flight’ response and don’t have any access to our prefrontal cortex, we are coming from a brain that is pumping cortisol and that leads to burnout,” said Dr. Rockwell.

“Any fight or flight response leaves a mark on your body,” Dr. Wener echoed. “When we go into our state of deep rest in the meditation practice, which is two to five times more restful than sleep, it heals those stress scars.”
 

Making time for mindfulness

Prescribing mindfulness for physicians is not new. Molecular biologist Jon Kabat-Zinn, PhD, developed Mindfulness-Based Stress Reduction (MBSR) in 1979, a practice that incorporates mindfulness exercises to help people become familiar with their behavior patterns in stressful situations. Thus, instead of reacting, they can respond with a clearer understanding of the circumstance. Dr. Kabat-Zinn initially targeted people with chronic health problems to help them cope with the effects of pain and the condition of their illness, but it has expanded to anyone experiencing challenges in their life, including physicians. A standard MBSR course runs 8 weeks, making it a commitment for most people. 

Mindfulness training requires that physicians use what they already have so little of: time.

Dr. Wener was able to take a sabbatical, embarking on a 3-month trip to India to immerse herself in the study of Vedic Meditation. Upon her return, Dr. Wener took a position at Emory University, Atlanta, and has launched a number of CME-accredited meditation courses and retreats. Unlike Dr. Kabat-Zinn, her programs are by physicians and for physicians. She also created an online version of the meditation course to make it more accessible. 

For these reasons, Kara Pepper, MD, an internist in outpatient primary care in Atlanta, was drawn to the meditation course. Dr. Pepper was 7 years into practice when she burned out. “The program dovetailed into my burnout recovery,” she said. “It allowed me space to separate myself from the thoughts I was having about work and just recognize them as just that – as thoughts.”

In the course, Dr. Wener teaches the REST Technique, which she says is different than mindfulness in that she encourages the mind to run rampant. “Trying to control the mind can feel very uncomfortable because we always have thoughts,” she says. “We can’t tell the mind to stop thinking just like we can’t tell the heart to stop beating.” Dr. Wener said the REST Technique lets “the mind swim downstream,” allowing the brain to go into a deep state of rest and start to heal from the scars caused by stress. 

Dr. Pepper said the self-paced online course gave her all the tools she needed, and it was pragmatic and evidence based. “I didn’t feel ‘woo’ or like another gimmick,” she said. Pepper, who continues to practice medicine, became a life coach in 2019 to teach others the skills she uses daily. 
 

An integrated strategy

Dr. Wener acknowledges that meditation is not the panacea for everyone’s burnout, which data support. In a review published in The American Journal of Medicine in 2019, Scott Yates, MD, MBA, from the Center for Executive Medicine in Plano, Tex., found that physicians who had adopted mediation and mindfulness training to decrease anxiety and perceived work stress only experienced modest benefits. In fact, Dr. Yates claims that there’s little data to suggest the long-term benefit of any particular stress management intervention in the prevention of burnout symptoms. 

“The often-repeated goals of the Triple Aim [enhancing patient experience, improving population health, and reducing costs] may be unreachable until we recognize and address burnout in health care providers,” Dr. Yates wrote. He recommends adding a fourth goal to specifically address physician wellness, which certainly could include mindfulness training and meditation.

Burnout coach, trainer, and consultant Dike Drummond, MD, also professes that physician wellness must be added as the key fourth ingredient to improving health care. “Burnout is a dilemma, a balancing act,” he said. “It takes an integrated strategy.” The CEO and founder of TheHappyMD.com, Dr. Drummond’s integrated strategy to stop physician burnout has been taught to more than 40,000 physicians in 175 organizations, and one element of that strategy can be mindfulness training. 

Dr. Drummond said he doesn’t use the word meditation “because that scares most people”; it takes a commitment and isn’t accessible for a lot of doctors. Instead, he coaches doctors to use a ‘single-breath’ technique to help them reset multiple times throughout the day. “I teach people how to breathe up to the top of their head and then down to the bottom of their feet,” Dr. Drummond said. He calls it the Squeegee Breath Technique because when they exhale, they “wipe away” anything that doesn’t need to be there right now. “If you happen to have a mindfulness practice like meditation, they work synergistically because the calmness you feel in your mediation is available to you at the bottom of these releasing breaths.”

Various studies and surveys provide great detail as to the “why” of physician burnout. And while mindfulness is not the sole answer, it’s something physicians can explore for themselves while health care as an industry looks for a more comprehensive solution. 

“It’s not rocket science,” Dr. Drummond insisted. “You want a different result? You’re not satisfied with the way things are now and you want to feel different? You absolutely must do something different.”

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

In 2011, the Mayo Clinic began surveying physicians about burnout and found 45% of physicians experienced at least one symptom, such as emotional exhaustion, finding work no longer meaningful, feelings of ineffectiveness, and depersonalizing patients. Associated manifestations can range from headache and insomnia to impaired memory and decreased attention. 

Marija Jovovic/Getty Images

Fast forward 10 years to the Medscape National Physician Burnout and Suicide Report, which found that a similar number of physicians (42%) feel burned out. The COVID-19 pandemic only added insult to injury. A Medscape survey that included nearly 5,000 U.S. physicians revealed that about two-thirds (64%) of them reported burnout had intensified during the crisis.

These elevated numbers are being labeled as “a public health crisis” for the impact widespread physician burnout could have on the health of the doctor and patient safety. The relatively consistent levels across the decade seem to suggest that, if health organizations are attempting to improve physician well-being, it doesn’t appear to be working, forcing doctors to find solutions for themselves.

Jill Wener, MD, considers herself part of the 45% burned out 10 years ago. She was working as an internist at Rush University Medical Center in Chicago, but the “existential reality of being a doctor in this world” was wearing on her. “Staying up with the literature, knowing that every day you’re going to go into work without knowing what you’re going to find, threats of lawsuits, the pressure of perfectionism,” Dr. Wener told this news organization. “By the time I hit burnout, everything made me feel like the world was crashing down on me.”

When Dr. Wener encountered someone who meditated twice a day, she was intrigued, even though the self-described “most Type-A, inside-the-box, nonspiritual type, anxious, linear-path doctor” didn’t think people like her could meditate. Dr. Wener is not alone in her hesitation to explore meditation as a means to help prevent burnout because the causes of burnout are primarily linked to external rather than internal factors. Issues including a loss of autonomy, the burden and distraction of electronic health records, and the intense pressure to comply with rules from the government are not things mindfulness can fix. 

And because the sources of burnout are primarily environmental and inherent to the current medical system, the suggestion that physicians need to fix themselves with meditation can come as a slap in the face. However, when up against a system slow to change, mindfulness can provide physicians access to the one thing they can control: How they perceive and react to what’s in front of them.

At the recommendation of an acquaintance, Dr. Wener enrolled in a Vedic Meditation (also known as Conscious Health Meditation) course taught by Light Watkins, a well-known traveling instructor, author, and speaker. By the second meeting she was successfully practicing 20 minutes twice a day. This form of mediation traces its roots to the Vedas, ancient Indian texts (also the foundation for yoga), and uses a mantra to settle the mind, transitioning to an awake state of inner contentment. 

Three weeks later, Dr. Wener’s daily crying jags ended as did her propensity for road rage. “I felt like I was on the cusp of something life-changing, I just didn’t understand it,” she recalled. “But I knew I was never going to give it up.”
 

Defining mindfulness

“Mindfulness is being able to be present in the moment that you’re in with acceptance of what it is and without judging it,” said Donna Rockwell, PsyD, a leading mindfulness meditation teacher. The practice of mindfulness is really meditation. Dr. Rockwell explained that the noise of our mind is most often focused on either the past or the future. “We’re either bemoaning something that happened earlier or we’re catastrophizing the future,” she said, which prevents us from being present in the moment. 

Meditation allows you to notice when your mind has drifted from the present moment into the past or future. “You gently notice it, label it with a lot of self-compassion, and then bring your mind back by focusing on your breath – going out, going in – and the incoming stimuli through your five senses,” said Dr. Rockwell. “When you’re doing that, you can’t be in the past or future.”

Dr. Rockwell also pointed out that we constantly categorize incoming data of the moment as either “good for me or bad for me,” which gets in the way of simply being present for what you’re facing. “When you’re more fully present, you become more skillful and able to do what this moment is asking of you,” she said. Being mindful allows us to better navigate incoming stimuli, which could be a “code blue” in the ED or a patient who needs another 2 minutes during an office visit. 

When Dr. Wener was burned out, she felt unable to adapt whenever something unexpected happened. “When you have no emotional reserves, everything feels like a big deal,” she said. “The meditation gave me what we call adaptation energy; it filled up my tank and kept me from feeling like I was going to lose it at 10 o’clock in the morning.”

Dr. Rockwell explained burnout as an overactive fight or flight response activated by the amygdala. It starts pumping cortisol, our pupils dilate, and our pores open. The prefrontal cortex is offline when we’re experiencing this physiological response because they both can’t be operational at the same time. “When we’re constantly in a ‘fight or flight’ response and don’t have any access to our prefrontal cortex, we are coming from a brain that is pumping cortisol and that leads to burnout,” said Dr. Rockwell.

“Any fight or flight response leaves a mark on your body,” Dr. Wener echoed. “When we go into our state of deep rest in the meditation practice, which is two to five times more restful than sleep, it heals those stress scars.”
 

Making time for mindfulness

Prescribing mindfulness for physicians is not new. Molecular biologist Jon Kabat-Zinn, PhD, developed Mindfulness-Based Stress Reduction (MBSR) in 1979, a practice that incorporates mindfulness exercises to help people become familiar with their behavior patterns in stressful situations. Thus, instead of reacting, they can respond with a clearer understanding of the circumstance. Dr. Kabat-Zinn initially targeted people with chronic health problems to help them cope with the effects of pain and the condition of their illness, but it has expanded to anyone experiencing challenges in their life, including physicians. A standard MBSR course runs 8 weeks, making it a commitment for most people. 

Mindfulness training requires that physicians use what they already have so little of: time.

Dr. Wener was able to take a sabbatical, embarking on a 3-month trip to India to immerse herself in the study of Vedic Meditation. Upon her return, Dr. Wener took a position at Emory University, Atlanta, and has launched a number of CME-accredited meditation courses and retreats. Unlike Dr. Kabat-Zinn, her programs are by physicians and for physicians. She also created an online version of the meditation course to make it more accessible. 

For these reasons, Kara Pepper, MD, an internist in outpatient primary care in Atlanta, was drawn to the meditation course. Dr. Pepper was 7 years into practice when she burned out. “The program dovetailed into my burnout recovery,” she said. “It allowed me space to separate myself from the thoughts I was having about work and just recognize them as just that – as thoughts.”

In the course, Dr. Wener teaches the REST Technique, which she says is different than mindfulness in that she encourages the mind to run rampant. “Trying to control the mind can feel very uncomfortable because we always have thoughts,” she says. “We can’t tell the mind to stop thinking just like we can’t tell the heart to stop beating.” Dr. Wener said the REST Technique lets “the mind swim downstream,” allowing the brain to go into a deep state of rest and start to heal from the scars caused by stress. 

Dr. Pepper said the self-paced online course gave her all the tools she needed, and it was pragmatic and evidence based. “I didn’t feel ‘woo’ or like another gimmick,” she said. Pepper, who continues to practice medicine, became a life coach in 2019 to teach others the skills she uses daily. 
 

An integrated strategy

Dr. Wener acknowledges that meditation is not the panacea for everyone’s burnout, which data support. In a review published in The American Journal of Medicine in 2019, Scott Yates, MD, MBA, from the Center for Executive Medicine in Plano, Tex., found that physicians who had adopted mediation and mindfulness training to decrease anxiety and perceived work stress only experienced modest benefits. In fact, Dr. Yates claims that there’s little data to suggest the long-term benefit of any particular stress management intervention in the prevention of burnout symptoms. 

“The often-repeated goals of the Triple Aim [enhancing patient experience, improving population health, and reducing costs] may be unreachable until we recognize and address burnout in health care providers,” Dr. Yates wrote. He recommends adding a fourth goal to specifically address physician wellness, which certainly could include mindfulness training and meditation.

Burnout coach, trainer, and consultant Dike Drummond, MD, also professes that physician wellness must be added as the key fourth ingredient to improving health care. “Burnout is a dilemma, a balancing act,” he said. “It takes an integrated strategy.” The CEO and founder of TheHappyMD.com, Dr. Drummond’s integrated strategy to stop physician burnout has been taught to more than 40,000 physicians in 175 organizations, and one element of that strategy can be mindfulness training. 

Dr. Drummond said he doesn’t use the word meditation “because that scares most people”; it takes a commitment and isn’t accessible for a lot of doctors. Instead, he coaches doctors to use a ‘single-breath’ technique to help them reset multiple times throughout the day. “I teach people how to breathe up to the top of their head and then down to the bottom of their feet,” Dr. Drummond said. He calls it the Squeegee Breath Technique because when they exhale, they “wipe away” anything that doesn’t need to be there right now. “If you happen to have a mindfulness practice like meditation, they work synergistically because the calmness you feel in your mediation is available to you at the bottom of these releasing breaths.”

Various studies and surveys provide great detail as to the “why” of physician burnout. And while mindfulness is not the sole answer, it’s something physicians can explore for themselves while health care as an industry looks for a more comprehensive solution. 

“It’s not rocket science,” Dr. Drummond insisted. “You want a different result? You’re not satisfied with the way things are now and you want to feel different? You absolutely must do something different.”

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