Symptoms of obstructive sleep apnea (OSA) were significantly more common in children with autism spectrum disorder (ASD), compared with controls, based on data from 166 individuals up to age 18 years.

Autism spectrum disorder affects approximately 1 in 54 children in the United States, and recent studies have shown an increased risk of obstructive sleep apnea in this population, compared with the general pediatric population, wrote Pooja Santapuram, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.

In a study published in the International Journal of Pediatric Ototrhinolaryngology , the researchers reviewed data from 166 children and adolescents up to 18 years of age with OSA who underwent adenotonsillectomy at a single center between 2019 and 2021. The primary objective was to assess OSA symptoms in children with and without ASD. The study population included 75 children with ASD and 91 controls. The average age of both the ASD group and control group was approximately 73 months.
 

OSA meets ASD

Obstructive sleep apnea is common in autism spectrum disorder. Children with OSA can present with a range of symptoms, including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. To do so, a retrospective chart review was conducted on the 166 pediatric patients.

Overall, significantly more OSA symptoms were reported in children with ASD, compared with controls (P < .001).

Lower autism severity was associated with an increased number of reported OSA symptoms (P = .006). There was not a significant between-group difference in age at OSA diagnosis (P = .999); however, lower autism severity was also associated with an increased age at diagnosis (P = .002). These findings suggest that OSA may present with a higher symptom burden in children with ASD, and children with lower ASD severity often experience delays in OSA diagnosis.

Interestingly, despite the known associations between obesity and OSA, children with an increased body mass index were not diagnosed with OSA at an earlier age in this sample population, the researchers indicated.

Because the current study revealed that children with less severe ASD are more likely to report an increased number of OSA symptoms and be diagnosed at a later age than children without ASD, clinicians should have a heightened sense for OSA evaluation in children with ASD, particularly in children with a lower severity of ASD and an increased BMI, the researchers concluded.

The research study was not externally funded, and the researchers reported that they had no conflicts of interest.

Symptoms of obstructive sleep apnea (OSA) were significantly more common in children with autism spectrum disorder (ASD), compared with controls, based on data from 166 individuals up to age 18 years.

Autism spectrum disorder affects approximately 1 in 54 children in the United States, and recent studies have shown an increased risk of obstructive sleep apnea in this population, compared with the general pediatric population, wrote Pooja Santapuram, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.

In a study published in the International Journal of Pediatric Ototrhinolaryngology , the researchers reviewed data from 166 children and adolescents up to 18 years of age with OSA who underwent adenotonsillectomy at a single center between 2019 and 2021. The primary objective was to assess OSA symptoms in children with and without ASD. The study population included 75 children with ASD and 91 controls. The average age of both the ASD group and control group was approximately 73 months.
 

OSA meets ASD

Obstructive sleep apnea is common in autism spectrum disorder. Children with OSA can present with a range of symptoms, including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. To do so, a retrospective chart review was conducted on the 166 pediatric patients.

Overall, significantly more OSA symptoms were reported in children with ASD, compared with controls (P < .001).

Lower autism severity was associated with an increased number of reported OSA symptoms (P = .006). There was not a significant between-group difference in age at OSA diagnosis (P = .999); however, lower autism severity was also associated with an increased age at diagnosis (P = .002). These findings suggest that OSA may present with a higher symptom burden in children with ASD, and children with lower ASD severity often experience delays in OSA diagnosis.

Interestingly, despite the known associations between obesity and OSA, children with an increased body mass index were not diagnosed with OSA at an earlier age in this sample population, the researchers indicated.

Because the current study revealed that children with less severe ASD are more likely to report an increased number of OSA symptoms and be diagnosed at a later age than children without ASD, clinicians should have a heightened sense for OSA evaluation in children with ASD, particularly in children with a lower severity of ASD and an increased BMI, the researchers concluded.

The research study was not externally funded, and the researchers reported that they had no conflicts of interest.

Symptoms of obstructive sleep apnea (OSA) were significantly more common in children with autism spectrum disorder (ASD), compared with controls, based on data from 166 individuals up to age 18 years.

Autism spectrum disorder affects approximately 1 in 54 children in the United States, and recent studies have shown an increased risk of obstructive sleep apnea in this population, compared with the general pediatric population, wrote Pooja Santapuram, MD, of Vanderbilt University, Nashville, Tenn., and colleagues.

In a study published in the International Journal of Pediatric Ototrhinolaryngology , the researchers reviewed data from 166 children and adolescents up to 18 years of age with OSA who underwent adenotonsillectomy at a single center between 2019 and 2021. The primary objective was to assess OSA symptoms in children with and without ASD. The study population included 75 children with ASD and 91 controls. The average age of both the ASD group and control group was approximately 73 months.
 

OSA meets ASD

Obstructive sleep apnea is common in autism spectrum disorder. Children with OSA can present with a range of symptoms, including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. To do so, a retrospective chart review was conducted on the 166 pediatric patients.

Overall, significantly more OSA symptoms were reported in children with ASD, compared with controls (P < .001).

Lower autism severity was associated with an increased number of reported OSA symptoms (P = .006). There was not a significant between-group difference in age at OSA diagnosis (P = .999); however, lower autism severity was also associated with an increased age at diagnosis (P = .002). These findings suggest that OSA may present with a higher symptom burden in children with ASD, and children with lower ASD severity often experience delays in OSA diagnosis.

Interestingly, despite the known associations between obesity and OSA, children with an increased body mass index were not diagnosed with OSA at an earlier age in this sample population, the researchers indicated.

Because the current study revealed that children with less severe ASD are more likely to report an increased number of OSA symptoms and be diagnosed at a later age than children without ASD, clinicians should have a heightened sense for OSA evaluation in children with ASD, particularly in children with a lower severity of ASD and an increased BMI, the researchers concluded.

The research study was not externally funded, and the researchers reported that they had no conflicts of interest.

Hyaluronic acid is the most common filler used in the United States for cosmetic procedures. As cosmetic treatments continue to grow and the filler market expands, the use of hyaluronidase for the reversal of facial hyaluronic acid fillers is becoming more widespread. However, there has been little research and there are no formal clinical guidelines on its use. Hyaluronidase is approved by the Food and Drug Administration for several indications, but its use in cosmetic procedures is off-label.

Hyaluronic acid filler complications can be local and transient or delayed and/or dangerous. Local reactions generally improve over time or respond to symptomatic care. But granulomatous reactions, misplaced injection, adverse aesthetic outcomes, and vascular occlusion are some of the detrimental outcomes that require immediate treatment, often using hyaluronidase, a naturally occurring enzyme that degrades hyaluronic acid.

Hyaluronic acid products vary in concentration, cross-linking, type of cross-linker used, and particle size, and therefore display different degradation patterns with hyaluronidase. The three hyaluronidase products available also vary in concentration, source, and enzyme activity. Hyaluronidase has a half-life of 2 minutes but has a duration of action of 24-48 hours depending on the product used.

In an interesting study by Casabona G et al., the dose and activity of five hyaluronidase products available worldwide were used to degrade five different fillers (Juvederm Volbella, Voluma, and Ultraplus; Belotero, and Belotero Balance) with various concentrations and cross-linking in human skin. The results showed that the Vycross products (Juvederm Voluma) are the least sensitive to hyaluronidase and require the greatest concentration of hyaluronidase and a longer time for dissolution requiring up to three times more hyaluronidase to degrade the same volume of other hyaluronic acid products.

In addition, the ovine hyaluronidase product marketed in the United States as Vitrase had the greatest activity against the range of hyaluronic acids used in the trial. Higher concentrations of hyaluronidase also could produce type-I hypersensitivity reactions and angioedema in susceptible patients as evidenced by eosinophilic tissue reactions at concentrations greater than 300 IU.

Hyaluronidase is stored at cool temperatures (35-46° F). It can be reconstituted with saline, water, or bacteriostatic saline for reducing injection site pain; however, it should not be mixed with local anesthetic. The volume of diluent used depends on the surface area treated and ranges from 1 mL to 10 mL. Smaller volumes are used for more concentrated local injection and larger volumes for more precise dosing.

For impending necrosis, hyaluronidase should be used within minutes to hours of blanching of the skin and the area should be flooded every 30 minutes until the tissue has reperfused. Depending on the type of filler used, the volume of injection varies and the area should continually be injected and tissue response observed. A high-dosed large-volume protocol allows the tissue perfusion to gradually infiltrate the vessel walls. Recommendations are 2 mL of bacteriostatic saline diluted with a vial of hyaluronidase. Retrobulbar injection of hyaluronidase within minutes of retinal artery occlusion in doses of 150-200 units in 2-4 mL of diluent into the inferolateral orbit by an experienced ophthalmologist or oculoplastic surgeon is recommended.

Although there is no consensus, there are various clinical studies using hyaluronidase dilutions varying between 5 and 30 units to break down 0.1mg/mL of hyaluronic acid for the reversal of facial hyaluronic acid fillers. In my clinical experience, the recommendation is that, apart from necrosis, the concentration used is titrated to clinical efficacy, which can also be done over multiple appointments every 48 hours until the desired outcome is achieved.

Complications from hyaluronidase injection include local tissue erythema, edema, pain, allergic reactions, and anaphylaxis. An intradermal patch test of 10-20 units of hyaluronidase in the forearm can be done in patients with a history of allergy to hyaluronidase, which, in people with sensitivity, results in a wheal within 30 minutes of injection. If a patient has a positive patch test, hyaluronidase cannot be used. In addition, a history of allergic reactions to bees may pose a heightened reaction to hyaluronidase and is a contraindication to use.

It is recommended that any practitioner using hyaluronic acid fillers keep 2-3 vials of hyaluronidase available at all times in the event of a vascular emergency. Stability, storage, and expiration dates should also be monitored closely.

Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to them at [email protected]. Dr. Talakoub has no relevant disclosures.

References

Casabona G et al. Dermatol Surg. 2018 Nov;44 Suppl 1:S42-S50.

DeLorenzi C. Aesthet Surg J. 2017 Jul 1;37(7):814-25.

Juhász MLW et al. Dermatol Surg. 2017 Jun;43(6):841-7.

King M. J Clin Aesthet Dermatol. 2016 Nov; 9(11):E6–8.

Kim M et al. J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-8.

Hyaluronic acid is the most common filler used in the United States for cosmetic procedures. As cosmetic treatments continue to grow and the filler market expands, the use of hyaluronidase for the reversal of facial hyaluronic acid fillers is becoming more widespread. However, there has been little research and there are no formal clinical guidelines on its use. Hyaluronidase is approved by the Food and Drug Administration for several indications, but its use in cosmetic procedures is off-label.

Hyaluronic acid filler complications can be local and transient or delayed and/or dangerous. Local reactions generally improve over time or respond to symptomatic care. But granulomatous reactions, misplaced injection, adverse aesthetic outcomes, and vascular occlusion are some of the detrimental outcomes that require immediate treatment, often using hyaluronidase, a naturally occurring enzyme that degrades hyaluronic acid.

Hyaluronic acid products vary in concentration, cross-linking, type of cross-linker used, and particle size, and therefore display different degradation patterns with hyaluronidase. The three hyaluronidase products available also vary in concentration, source, and enzyme activity. Hyaluronidase has a half-life of 2 minutes but has a duration of action of 24-48 hours depending on the product used.

In an interesting study by Casabona G et al., the dose and activity of five hyaluronidase products available worldwide were used to degrade five different fillers (Juvederm Volbella, Voluma, and Ultraplus; Belotero, and Belotero Balance) with various concentrations and cross-linking in human skin. The results showed that the Vycross products (Juvederm Voluma) are the least sensitive to hyaluronidase and require the greatest concentration of hyaluronidase and a longer time for dissolution requiring up to three times more hyaluronidase to degrade the same volume of other hyaluronic acid products.

In addition, the ovine hyaluronidase product marketed in the United States as Vitrase had the greatest activity against the range of hyaluronic acids used in the trial. Higher concentrations of hyaluronidase also could produce type-I hypersensitivity reactions and angioedema in susceptible patients as evidenced by eosinophilic tissue reactions at concentrations greater than 300 IU.

Hyaluronidase is stored at cool temperatures (35-46° F). It can be reconstituted with saline, water, or bacteriostatic saline for reducing injection site pain; however, it should not be mixed with local anesthetic. The volume of diluent used depends on the surface area treated and ranges from 1 mL to 10 mL. Smaller volumes are used for more concentrated local injection and larger volumes for more precise dosing.

For impending necrosis, hyaluronidase should be used within minutes to hours of blanching of the skin and the area should be flooded every 30 minutes until the tissue has reperfused. Depending on the type of filler used, the volume of injection varies and the area should continually be injected and tissue response observed. A high-dosed large-volume protocol allows the tissue perfusion to gradually infiltrate the vessel walls. Recommendations are 2 mL of bacteriostatic saline diluted with a vial of hyaluronidase. Retrobulbar injection of hyaluronidase within minutes of retinal artery occlusion in doses of 150-200 units in 2-4 mL of diluent into the inferolateral orbit by an experienced ophthalmologist or oculoplastic surgeon is recommended.

Although there is no consensus, there are various clinical studies using hyaluronidase dilutions varying between 5 and 30 units to break down 0.1mg/mL of hyaluronic acid for the reversal of facial hyaluronic acid fillers. In my clinical experience, the recommendation is that, apart from necrosis, the concentration used is titrated to clinical efficacy, which can also be done over multiple appointments every 48 hours until the desired outcome is achieved.

Complications from hyaluronidase injection include local tissue erythema, edema, pain, allergic reactions, and anaphylaxis. An intradermal patch test of 10-20 units of hyaluronidase in the forearm can be done in patients with a history of allergy to hyaluronidase, which, in people with sensitivity, results in a wheal within 30 minutes of injection. If a patient has a positive patch test, hyaluronidase cannot be used. In addition, a history of allergic reactions to bees may pose a heightened reaction to hyaluronidase and is a contraindication to use.

It is recommended that any practitioner using hyaluronic acid fillers keep 2-3 vials of hyaluronidase available at all times in the event of a vascular emergency. Stability, storage, and expiration dates should also be monitored closely.

Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to them at [email protected]. Dr. Talakoub has no relevant disclosures.

References

Casabona G et al. Dermatol Surg. 2018 Nov;44 Suppl 1:S42-S50.

DeLorenzi C. Aesthet Surg J. 2017 Jul 1;37(7):814-25.

Juhász MLW et al. Dermatol Surg. 2017 Jun;43(6):841-7.

King M. J Clin Aesthet Dermatol. 2016 Nov; 9(11):E6–8.

Kim M et al. J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-8.

Hyaluronic acid is the most common filler used in the United States for cosmetic procedures. As cosmetic treatments continue to grow and the filler market expands, the use of hyaluronidase for the reversal of facial hyaluronic acid fillers is becoming more widespread. However, there has been little research and there are no formal clinical guidelines on its use. Hyaluronidase is approved by the Food and Drug Administration for several indications, but its use in cosmetic procedures is off-label.

Hyaluronic acid filler complications can be local and transient or delayed and/or dangerous. Local reactions generally improve over time or respond to symptomatic care. But granulomatous reactions, misplaced injection, adverse aesthetic outcomes, and vascular occlusion are some of the detrimental outcomes that require immediate treatment, often using hyaluronidase, a naturally occurring enzyme that degrades hyaluronic acid.

Hyaluronic acid products vary in concentration, cross-linking, type of cross-linker used, and particle size, and therefore display different degradation patterns with hyaluronidase. The three hyaluronidase products available also vary in concentration, source, and enzyme activity. Hyaluronidase has a half-life of 2 minutes but has a duration of action of 24-48 hours depending on the product used.

In an interesting study by Casabona G et al., the dose and activity of five hyaluronidase products available worldwide were used to degrade five different fillers (Juvederm Volbella, Voluma, and Ultraplus; Belotero, and Belotero Balance) with various concentrations and cross-linking in human skin. The results showed that the Vycross products (Juvederm Voluma) are the least sensitive to hyaluronidase and require the greatest concentration of hyaluronidase and a longer time for dissolution requiring up to three times more hyaluronidase to degrade the same volume of other hyaluronic acid products.

In addition, the ovine hyaluronidase product marketed in the United States as Vitrase had the greatest activity against the range of hyaluronic acids used in the trial. Higher concentrations of hyaluronidase also could produce type-I hypersensitivity reactions and angioedema in susceptible patients as evidenced by eosinophilic tissue reactions at concentrations greater than 300 IU.

Hyaluronidase is stored at cool temperatures (35-46° F). It can be reconstituted with saline, water, or bacteriostatic saline for reducing injection site pain; however, it should not be mixed with local anesthetic. The volume of diluent used depends on the surface area treated and ranges from 1 mL to 10 mL. Smaller volumes are used for more concentrated local injection and larger volumes for more precise dosing.

For impending necrosis, hyaluronidase should be used within minutes to hours of blanching of the skin and the area should be flooded every 30 minutes until the tissue has reperfused. Depending on the type of filler used, the volume of injection varies and the area should continually be injected and tissue response observed. A high-dosed large-volume protocol allows the tissue perfusion to gradually infiltrate the vessel walls. Recommendations are 2 mL of bacteriostatic saline diluted with a vial of hyaluronidase. Retrobulbar injection of hyaluronidase within minutes of retinal artery occlusion in doses of 150-200 units in 2-4 mL of diluent into the inferolateral orbit by an experienced ophthalmologist or oculoplastic surgeon is recommended.

Although there is no consensus, there are various clinical studies using hyaluronidase dilutions varying between 5 and 30 units to break down 0.1mg/mL of hyaluronic acid for the reversal of facial hyaluronic acid fillers. In my clinical experience, the recommendation is that, apart from necrosis, the concentration used is titrated to clinical efficacy, which can also be done over multiple appointments every 48 hours until the desired outcome is achieved.

Complications from hyaluronidase injection include local tissue erythema, edema, pain, allergic reactions, and anaphylaxis. An intradermal patch test of 10-20 units of hyaluronidase in the forearm can be done in patients with a history of allergy to hyaluronidase, which, in people with sensitivity, results in a wheal within 30 minutes of injection. If a patient has a positive patch test, hyaluronidase cannot be used. In addition, a history of allergic reactions to bees may pose a heightened reaction to hyaluronidase and is a contraindication to use.

It is recommended that any practitioner using hyaluronic acid fillers keep 2-3 vials of hyaluronidase available at all times in the event of a vascular emergency. Stability, storage, and expiration dates should also be monitored closely.

Dr. Talakoub and Naissan O. Wesley, MD, are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to them at [email protected]. Dr. Talakoub has no relevant disclosures.

References

Casabona G et al. Dermatol Surg. 2018 Nov;44 Suppl 1:S42-S50.

DeLorenzi C. Aesthet Surg J. 2017 Jul 1;37(7):814-25.

Juhász MLW et al. Dermatol Surg. 2017 Jun;43(6):841-7.

King M. J Clin Aesthet Dermatol. 2016 Nov; 9(11):E6–8.

Kim M et al. J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-8.

Adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease, a new study suggests.

The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.

“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.

They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.

They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.

However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.

“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.

The study was published online in the Journal of the American College of Cardiology.

The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.

“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.  

They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.

They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.

For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).

Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.

Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.

Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.

When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.

In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.

An indirect measure of triglycerides

Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.

“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”

He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.  

“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.

While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.

“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.  

This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.

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

Adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease, a new study suggests.

The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.

“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.

They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.

They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.

However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.

“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.

The study was published online in the Journal of the American College of Cardiology.

The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.

“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.  

They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.

They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.

For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).

Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.

Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.

Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.

When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.

In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.

An indirect measure of triglycerides

Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.

“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”

He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.  

“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.

While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.

“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.  

This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.

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

Adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease, a new study suggests.

The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.

“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.

They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.

They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.

However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.

“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.

The study was published online in the Journal of the American College of Cardiology.

The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.

“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.  

They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.

They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.

For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).

Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.

Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.

Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.

When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.

In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.

An indirect measure of triglycerides

Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.

“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”

He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.  

“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.

While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.

“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.  

This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.

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

CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.

The two conditions have historically been lumped together when studying treatment outcomes, but more recent research has shown key differences between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.

“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.

The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.

The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.

The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.

A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.

Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.

So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.

Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.

There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.

The study received no external funding.

CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.

The two conditions have historically been lumped together when studying treatment outcomes, but more recent research has shown key differences between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.

“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.

The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.

The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.

The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.

A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.

Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.

So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.

Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.

There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.

The study received no external funding.

CHICAGO – Metastatic invasive lobular breast cancers (ILC) that are hormone receptor (HR)-positive and HER2-negative have therapeutic outcomes similar to those of invasive ductal cancer (IDC) following treatment with endocrine therapy combined with a CDK4/6 inhibitor, mTOR inhibitor, or PI3K inhibitor, according to a new retrospective analysis of patients treated at MD Anderson Cancer Center.

The two conditions have historically been lumped together when studying treatment outcomes, but more recent research has shown key differences between the two subtypes, according to Jason A. Mouabbi, MD, who presented the results at the annual meeting of the American Society of Clinical Oncology.

“All the studies that were done were driven by ductal patients, so you can never take conclusions for the lobular patients. We have a big database at MD Anderson, so we can really study a large number of patients and get some signals whether or not patients would benefit from that therapy or not,” said Dr. Mouabbi, a lobular breast cancer specialist at MD Anderson Cancer Center.

The results of the study are important since patients often come to physicians with sophisticated understanding of their disease, he said. Patients with lobular cancer naturally wonder if a therapeutic regimen tested primarily in IDC will benefit them. “For the longest time, we said, ‘we have no data,’ ” said Dr. Mouabbi.

The new study should offer patients and physicians some reassurance. “We found that all of them benefit from it and most importantly, they all benefit from it (with) the same magnitude,” Dr. Mouabbi said.

The researchers analyzed data from 2,971 patients (82% IDC, 14% ILC, 4% mixed) treated between 2010 and 2021. The median age was 50 in all groups. Eighty percent were White, 10% were Hispanic, and 5% were Black. Ninety-nine percent had estrogen receptor (ER) + tumors, and 88% had progesterone positive (PR) + tumors.

A total of 1,895 patients received CDK4/6 inhibitors, 1,027 received everolimus, and 49 received alpelisib. There was no statistically significant difference in overall survival or progression-free survival between the two cancer types in any of the treatment groups.

Despite the similar outcomes, the two conditions remain unique. IDC is a disease of cells from the ducts that deliver milk, while ILC arises in cells that produce milk. Nearly 95% of ILC cases are hormone-positive, compared to 50%-55% of IDC.

So, while existing treatments seem to benefit both groups, there are nonetheless plans to develop therapeutic strategies tailored to lobular cancer.

Dr. Mouabbi’s group has compared molecular profiles of ILC and IDC tumors to better understand how to target them individually. Almost all ILC cancers have a mutation in a gene called CDH1, which leads to loss of an anchoring protein. They believe this causes a unique growth pattern of thin tendrils, rather than the onion-like growths of IDC. A therapy targeting this mutation could provide a specific benefit for lobular breast cancer.

There are other differences: PI3 kinases are mutated in about 60% of ILC tumors, versus about 30% of IDC tumors, and other genes mutated at lower frequencies are also different between the two subtypes. “So there are a lot of (approaches) we are trying to initiate in lobular cancer because we have awareness now that they are different,” Dr. Mouabbi said.

The study received no external funding.

A study of elderly patients with HER2-positive/HR-negative metastatic breast cancer finds a significantly shorter median overall survival in actual clinical practice than younger counterparts.

After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.

For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.

The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).

Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.

“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.

According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.

Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.

“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.

While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.

“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.

A study of elderly patients with HER2-positive/HR-negative metastatic breast cancer finds a significantly shorter median overall survival in actual clinical practice than younger counterparts.

After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.

For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.

The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).

Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.

“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.

According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.

Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.

“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.

While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.

“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.

A study of elderly patients with HER2-positive/HR-negative metastatic breast cancer finds a significantly shorter median overall survival in actual clinical practice than younger counterparts.

After 46 months of treatment, the survival rate was only 25%, according to a study presented in June at the annual meeting of the American Society of Clinical Oncology. The finding suggests that older age is an important prognostic factor for breast cancer survival, said study author Zhonghui Jenny Ou, a doctoral candidate at the Massachusetts College of Pharmacy and Health Sciences in Boston.

For comparison, Ms. Ou cited the CLEOPATRA trial which showed a median overall survival of 57.1 months for patients who were treated with pertuzumab, docetaxel and trastuzumab versus 40.8 months for placebo with docetaxel plus trastuzumab.

The Ou study is based on an analysis of data between 2012 and 2016 from the SEER-Medicare database. The final analysis included 73 women (average age 75 years at diagnosis) with early-stage HER2-positive/HR-negative metastatic breast cancer. Fifty-six women were treated with trastuzumab with pertuzumab and chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The longest length of treatment with trastuzumab was over 44 months. And, the median follow-up for overall survival was 13 months (95% confidence interval, 12.7-18.7).

Between 2012 and 2016, five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart disease.

“While there are many clinical trials about HER2-positive metastatic breast cancer, these trials were all performed in younger and relatively healthier patients. Few studies included elderly patients 65 years or older,” Ms. Ou said.

According to the American Cancer Society, 31% of all newly diagnosed breast cancer cases are in women who are 70 years old or older, yet 47% of all breast cancer deaths each year are in women in this age group.

Undertreatment and lower treatment intensity have been cited by other studies as possible contributing factors to lower overall survival rates, but breast cancer in elderly women is a complex and understudied subject. Why the mortality rates for elderly women are disproportionately higher than those of younger women is attributable to a number of reasons, write the authors of one of the most recent studies on the subject.

“It is well established that receipt of adjuvant chemotherapy, trastuzumab, and hormonal therapy reduces risk of recurrence and death across all age groups, yet multiple studies document suboptimal systemic treatment and adherence for older patients, including omission of efficacious treatments, receipt of lower intensity and/or nonguideline treatment, or poor adherence to hormonal therapy,” Freedman et al. wrote in the May 15, 2018, issue of the journal Cancer.

While the Ou study sample size was small, the study’s real-world analysis is telling, Ms. Ou said.

“The major limitation of this study is that it has – after applying all the eligibility criteria to the 170,516 breast cancer patients from the SEER-Medicare database between 2012 and 2016 – a study population of just 73 patients. The number is sufficient to do survival analysis,” she said.

Eight-year follow-up of the ASTRRA trial confirmed and extended support for adding 2 years of ovarian function suppression with goserelin to tamoxifen, compared with tamoxifen alone.

“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.

The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.

Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.

Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).

The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”

A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.

Eight-year follow-up of the ASTRRA trial confirmed and extended support for adding 2 years of ovarian function suppression with goserelin to tamoxifen, compared with tamoxifen alone.

“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.

The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.

Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.

Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).

The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”

A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.

Eight-year follow-up of the ASTRRA trial confirmed and extended support for adding 2 years of ovarian function suppression with goserelin to tamoxifen, compared with tamoxifen alone.

“Adding ovarian suppression to tamoxifen should be considered for this population of women,” said senior author Hee Jeong Kim, MD, a breast cancer surgeon with the Asan Medical Center, Seoul, South Korea. Dr. Kim presented the data earlier this month at the annual meeting of the American Society of Clinical Oncology.

The median disease-free survival rate of 85.4% for tamoxifen plus ovarian function suppression versus 80.2% for tamoxifen alone (HR, 0.67; 95% confidence interval, 0.514-0.869; P = .0027) was consistent with recent findings from SOFT (Suppression of Ovarian Function Trial), which also showed a clear survival benefit in breast cancer events with the addition of ovarian function suppression to tamoxifen for women who remain premenopausal after chemotherapy. SOFT trial analyses of disease-free survival at 5 and 8 years demonstrated hazard ratios of 0.82 and 0.76 respectively.

Dr. Kim’s study is a post-trial follow-up of the ASTRRA trial, or the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, which randomly assigned 1,298 patients with breast cancer in a one-to-one ratio to receive tamoxifen only (n = 647) or tamoxifen plus ovarian function suppression (n = 635). The primary endpoint was disease-free survival and the secondary endpoint was overall survival.

Earlier ASTRRA analysis at 5-year follow-up had shown disease-free survival rates of 89.9% for tamoxifen plus ovarian function suppression versus 87.2% for tamoxifen alone in women with hormone-sensitive breast cancer who remained premenopausal or had premenopausal status restored after chemotherapy. Overall survival, a secondary endpoint, also favored adding ovarian function suppression (HR, 0.31; 95% CI, 0.10-0.94; P = .029). The absolute difference for disease-free survival adding ovarian function suppression at the later median follow-up of 106.4 months was 5.2%. The difference at 5 years had been 2.7%, Dr. Kim pointed out. Also, these findings were calculated from time of enrollment. When calculated from time of randomization, the disease-free survival rates were 84.1% and 78.1%, respectively, for tamoxifen plus ovarian function suppression and tamoxifen alone, with a 6.0% absolute difference (HR, 0.67; 95% CI, 0.516-0.872); P = .0025).

The benefit of adding ovarian function suppression to tamoxifen for the secondary endpoint of overall survival at 8 years (96.5% versus 95.3%) did not achieve statistical significance (HR, 0.78; 95% CI, 0.486-1.253); P = .3). “Although it’s not statistically significant, there are absolute differences between the two groups favoring tamoxifen plus ovarian function suppression,” Dr. Kim said in an interview. She pointed out also that for distant metastasis-free survival the hazard ratio was 0.71, significantly favoring tamoxifen plus ovarian function suppression. “More than 95% were still surviving at 8 years with tamoxifen plus ovarian function suppression. So, we need more events to fully evaluate the overall survival benefit.”

A study limitation, Dr. Kim acknowledged in the interview, is that safety and adverse event data were not collected. “As ovarian function suppression has been widely used in clinical practice for decades, and the side effects of its relatively short-term use were considered to be well-understood in previous studies, we focused on the oncologic efficacy of ovarian function suppression in this study,” she said.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

A neighborhood analysis of socioeconomic status conducted in the Pittsburgh area found worse metastatic breast cancer survival outcomes among patients of low socioeconomic status. The findings suggest that race is not a relevant factor in outcomes.

“This study demonstrates that metastatic breast cancer patients of low socioeconomic status have worse outcomes than those with higher socioeconomic status at our center. It also underscores the idea that race is not so much a biological construct but more a consequence of socioeconomic issues. The effect of race is likely mediated by lower socioeconomic status,” said Susrutha Puthanmadhom Narayanan, MD, who presented the results of her study earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

“The current study should make clinicians cognizant of the potential for biases in the management of metastatic breast cancer in terms of socioeconomic status and race. One should think of socioeconomic status as a predictor of bad outcomes, almost like a comorbidity, and think of [associations between race and outcomes], as a consequence of socioeconomic inequality,” said Dr. Puthanmadhom Narayanan, who is an internal medicine resident at University of Pittsburgh Medical Center.

She and her colleagues intend to dig deeper into the relationships. “We are interested in looking at utilization of different treatment options for metastatic breast cancer between the socioeconomic status groups. In the preliminary analysis, we saw that ER-positive metastatic breast cancer patients with lower socioeconomic status get treated with tamoxifen more often than aromatase inhibitors and newer agents. And, we have plans to study stress signaling and inflammation as mediators of bad outcomes in the low socioeconomic status population,” Dr. Puthanmadhom Narayanan said.

In fact, that tendency for lower socioeconomic status patients to receive older treatments should be a call to action for physicians. “This study should make clinicians cognizant of the potential for biases in management of metastatic breast cancer in terms of socioeconomic status and race,” she said.

The study is based on an analysis of data from the Neighborhood Atlas in which a Neighborhood Deprivation Index (NDI) score was calculated. An NDI score in the bottom tertile meant that patients were better off than patients with mid to high range NDI scores. In this study, socioeconomic status was described as “low deprivation” or “high depreviation.” Higher deprivation correlated with lower overall survival. And, there were more Black patients in the higher deprivation group (10.5%), compared with the low deprivation group (3.7%). In multivariate Cox proportional hazard model, socioeconomic status, but not race, had a significant effect on overall survival (HR for high deprivation was 1.19 [95% confidence interval; 1.04-1.37], P = 0.01).

It included 1,246 patients who were treated at the University of Pittsburgh Medical Center between 2000 and 2017. Of 1,246 patients, 414 patients considered in the bottom tertile of NDI as having low deprivation, while 832 patients in the middle or top tertiles were classified as having high deprivation.

The two socioeconomic status groups were similar in baseline characteristics, with the exception of race: 10.5% of the high deprivation group were African American, compared with 3.7% of the low deprivation group (P =.000093).

Univariate analyses showed worse survival in both Black women and women in the lower socioeconomic status group, but a multivariate analysis found only socioeconomic status was associated with overall survival (hazard ratio for lower socioeconomic status, 1.19; P = .01).

The study had several strengths, according to Rachel Freedman, MD, MPH, who served as a discussant for the abstract. “It included both de novo and recurrent metastatic breast cancer, unlike previous studies based on the Surveillance, Epidemiology, and End Results (SEER) database that only included de novo cases. It also employed a novel tool to define socioeconomic status in the form of the Neighborhood Atlas. The study “adds more evidence that socioeconomic status likely mediates much of what we see when it comes to racial disparities,” said Dr. Freedman, who is a senior physician at Dana Farber Cancer Institute.

Nevertheless, more work needs to be done. Dr. Freedman pointed out that the current study did not include information on treatment.

The findings underscore the failure to date to address disparities in breast cancer treatment, an effort that is hampered by difficulty in teasing out complex factors that may impact survival. “We need to standardize the way that we collect social determinants of health and act upon findings, and we need to standardize patient navigation, and we need to commit as a community to diverse clinical trial populations,” Dr. Freedman said.

Dr. Narayanan has no relevant financial disclosures. Dr. Freedman is an employee and stockholder of Firefly Health.

The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).

Olivier Le Moal/Getty Images

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

BBS affects an estimated 1,500-2,500 people in the United States.

Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.

Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.

As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.

These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.

The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
 

Safety, effectiveness in 66-week trial in 44 patients

The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.

After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.

The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

• After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
• 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
• In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
• At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.

Setmelanotide is associated with the following warnings and precautions:

• Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
• Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
• Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
• Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.

The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.

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

The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).

Olivier Le Moal/Getty Images

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

BBS affects an estimated 1,500-2,500 people in the United States.

Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.

Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.

As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.

These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.

The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
 

Safety, effectiveness in 66-week trial in 44 patients

The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.

After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.

The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

• After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
• 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
• In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
• At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.

Setmelanotide is associated with the following warnings and precautions:

• Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
• Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
• Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
• Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.

The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.

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

The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).

Olivier Le Moal/Getty Images

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

BBS affects an estimated 1,500-2,500 people in the United States.

Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.

Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.

As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.

These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.

The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
 

Safety, effectiveness in 66-week trial in 44 patients

The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.

After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.

The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

• After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
• 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
• In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
• At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.

Setmelanotide is associated with the following warnings and precautions:

• Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
• Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
• Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
• Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.

The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.

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