Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

Intra-articular calcium crystal deposition is commonly seen in knee osteoarthritis, but its significance has been debated.

Now, a new study that relied on knee radiographs and bilateral knee CT imaging to evaluate 2,093 participants, including some with and without knee mineralization, has provided some new insights.

The study has addressed the longstanding question: Is the calcium deposition a cause or a consequence of the OA? “If it’s a cause, targeting it might be helpful,” Jean Liew, MD, MS, the study’s lead author and assistant professor of medicine at Boston University, said in an interview. “If a consequence of the OA, targeting is not going to help.”

In this new study, because of the use of advanced imaging, the researchers demonstrated a strong relationship of the presence of this calcification with different pain characteristics, said Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University, the corresponding author of the study who has focused on this research for many years. “This indicates this mineralization is not inconsequential.”

The bottom line? “Calcification in the knee may not be simply inert and an innocent bystander of longstanding OA,” Dr. Neogi said in an interview.
 

Study details

Dr. Neogi and colleagues evaluated 2,093 participants (mean age, 61 years; 57% female) with a mean body mass index of 28.8 kg/m². In all, 10.2% of knees had intra-articular mineralization. The data came from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. At baseline, participants had knee radiographs and bilateral knee CT scans, and pain assessments every 8 months for 2 years. The Boston University Calcium Knee Score was used to score the CT imaging. The researchers longitudinally examined the relationship of the CT-detected intra-articular mineralization to the risk of frequent knee pain, intermittent or constant knee pain worsening, and pain severity worsening. All analyses were adjusted for age, sex, body mass index, race, site, and Kellgren-Lawrence grade.

Having any mineralization in the cartilage was associated with a doubling of odds for having frequent knee pain (95% confidence interval, 1.38-2.78), and 1.86 times greater likelihood of more frequent intermittent or constant knee pain (95% CI, 1.20-2.78) over the 2 years of follow-up. Similar results were seen for the presence of any intra-articular mineralization in the meniscus or joint capsule. The higher the burden of mineralization anywhere within the knee was linked with higher odds for all pain outcomes, with odds ratios ranging from 2.14 to 2.21.
 

Perspective

“Because we used more sensitive imaging to pick up the calcification, we are able to more confidently evaluate this association,” Dr. Neogi said in an interview. The problem with prior studies was their reliance on plain radiographs, which are not sensitive enough to pick up this calcification.

Among the other strengths of the new research, she said, is that it was longitudinal, included more than 2,000 people and used multiple ways to look at the pain experience, getting consistent results.

“Here we are saying there seems to be clinical relevance [to the mineralization]. That’s not so surprising. We know there are other medical conditions in which calcium calcification can cause severe pain and inflammation.” The old term, pseudogout, is now called calcium pyrophosphate deposition disease.

The next steps of research, Dr. Neogi said, are to investigate the link of the mineralization to inflammation and its association to cartilage damage.
 

Could colchicine help?

In another recent study, researchers conducted a post hoc analysis of a randomized clinical trial of the anti-inflammatory drug colchicine, finding that the use of colchicine at 0.5 mg daily was associated with a lower incidence of total knee and hip replacements (TKR, THR). In that study, 2,762 participants received colchicine, while 2,760 received placebo during the median follow-up of 28.6 months. During the trial, TKR or THR was done in 68 patients (2.5%) of those in the treated group and 97 patients (3.5%) in the placebo groups. That resulted in an incidence rate difference of –0.40 [95% CI, –0.74 to –0.06 ] per 100 person-years.

The authors wrote that the results suggest that “colchicine may slow the progression of OA, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”
 

Independent perspective

The new Boston University study supports the idea that there may be a larger subset of patients that may have a calcium mineralization component, said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson. He reviewed both studies and provided perspective. He is an editorial advisory board member for MDedge Rheumatology.

courtesy Banner University Medical Group–Tucson

The study by Dr. Liew and colleagues shows that “there is an association of crystal deposition not just in the cartilage, but various parts of the joint.” He emphasized the study found only an association and that more study is needed.

As for the colchicine study, he said, it “really shows there is potential at least within some individuals where it may decrease symptoms to the point where people are less likely to need joint replacement.” That analysis follows some previous research, some of it shorter term, finding that colchicine was not beneficial.
 

Takeaways

Would colchicine be worth a try in patients who have knee pain and calcium mineral deposits?

Dr. Neogi noted that a formulation of colchicine (Lodoco) was recently approved by the Food and Drug Administration to reduce the risk of myocardial infarction and other cardiovascular disease. While she does not advocate adopting a practice without evidence, she suggested if someone has both mineralization and cardiovascular disease, along with difficulty managing symptoms with established treatments, it might be worth a try, if no contraindications exist.

Dr. Kwoh agreed it may be worth a try, given that it is “relatively safe and relatively inexpensive.”

On one point all agreed: More research is needed.

Dr. Kwoh, Dr. Neogi and Dr. Liew have no relevant disclosures.

New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.

“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.

“For the small minority of patients who remain symptomatic despite adequate biochemical replacement with levothyroxine, a trial of liothyronine/levothyroxine combination therapy under specialist supervision may be appropriate,” they wrote.

The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.

Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.

“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
 

Persistent symptoms drive pursuit of alternatives

T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.

Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.

Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.

However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.

In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).

DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.

The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.

In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”

However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:

• When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
• For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
• A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
• Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
• When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
• Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
• Given the short half-life of LT3, splitting doses across 24  hours is recommended for many people.

The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
 

Reasons for persistent symptoms are murky; don’t forget menopause

The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.

“In reality, many patients with subclinical hypothyroidism [TSH 5-10  mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.

“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.

In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.

“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.

“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.

And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.

“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”

Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.

Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.

“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.

“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.

An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance. 

Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
 

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

New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.

“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.

“For the small minority of patients who remain symptomatic despite adequate biochemical replacement with levothyroxine, a trial of liothyronine/levothyroxine combination therapy under specialist supervision may be appropriate,” they wrote.

The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.

Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.

“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
 

Persistent symptoms drive pursuit of alternatives

T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.

Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.

Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.

However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.

In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).

DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.

The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.

In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”

However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:

• When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
• For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
• A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
• Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
• When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
• Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
• Given the short half-life of LT3, splitting doses across 24  hours is recommended for many people.

The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
 

Reasons for persistent symptoms are murky; don’t forget menopause

The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.

“In reality, many patients with subclinical hypothyroidism [TSH 5-10  mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.

“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.

In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.

“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.

“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.

And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.

“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”

Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.

Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.

“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.

“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.

An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance. 

Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
 

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

New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.

“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.

“For the small minority of patients who remain symptomatic despite adequate biochemical replacement with levothyroxine, a trial of liothyronine/levothyroxine combination therapy under specialist supervision may be appropriate,” they wrote.

The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.

Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.

“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
 

Persistent symptoms drive pursuit of alternatives

T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.

Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.

Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.

However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.

In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).

DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.

The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.

In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”

However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:

• When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
• For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
• A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
• Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
• When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
• Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
• Given the short half-life of LT3, splitting doses across 24  hours is recommended for many people.

The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
 

Reasons for persistent symptoms are murky; don’t forget menopause

The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.

“In reality, many patients with subclinical hypothyroidism [TSH 5-10  mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.

“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.

In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.

“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.

“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.

And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.

“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”

Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.

Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.

“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.

“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.

An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance. 

Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
 

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

Key clinical point: Women who survive stages I-III breast cancer (BC) may experience improved survival outcomes on adhering to a low-carbohydrate diet, particularly one that is plant-rich.

Major finding: Compared with women having the highest carbohydrate intake, lowest protein intake, and lowest fat intake after BC diagnosis, those adhering to an overall low‐carbohydrate diet (hazard ratio [HR] 0.82; P_trend = .0001) and a plant‐rich low‐carbohydrate diet (HR 0.73; P_trend <.0001) had a significantly lower risk for all-cause mortality.

Study details: Findings are from an analysis of two ongoing cohort studies, the Nurses’ Health Study (NHS) and NHS II, including 9621 women with stages I-III BC, of which 1269 women died from BC.

Disclosures: This study was sponsored by the US National Institutes of Health and University of Toronto. Two authors declared being the founder of or receiving personal fees, nonfinancial support, and grants from various sources. The other authors declared no conflicts of interest.

Source: Farvid MS et al. Associations of low-carbohydrate diets with breast cancer survival. Cancer. 2023 (Jun 10). Doi: 10.1002/cncr.34819

Key clinical point: Women who survive stages I-III breast cancer (BC) may experience improved survival outcomes on adhering to a low-carbohydrate diet, particularly one that is plant-rich.

Major finding: Compared with women having the highest carbohydrate intake, lowest protein intake, and lowest fat intake after BC diagnosis, those adhering to an overall low‐carbohydrate diet (hazard ratio [HR] 0.82; P_trend = .0001) and a plant‐rich low‐carbohydrate diet (HR 0.73; P_trend <.0001) had a significantly lower risk for all-cause mortality.

Study details: Findings are from an analysis of two ongoing cohort studies, the Nurses’ Health Study (NHS) and NHS II, including 9621 women with stages I-III BC, of which 1269 women died from BC.

Disclosures: This study was sponsored by the US National Institutes of Health and University of Toronto. Two authors declared being the founder of or receiving personal fees, nonfinancial support, and grants from various sources. The other authors declared no conflicts of interest.

Source: Farvid MS et al. Associations of low-carbohydrate diets with breast cancer survival. Cancer. 2023 (Jun 10). Doi: 10.1002/cncr.34819

Key clinical point: Women who survive stages I-III breast cancer (BC) may experience improved survival outcomes on adhering to a low-carbohydrate diet, particularly one that is plant-rich.

Major finding: Compared with women having the highest carbohydrate intake, lowest protein intake, and lowest fat intake after BC diagnosis, those adhering to an overall low‐carbohydrate diet (hazard ratio [HR] 0.82; P_trend = .0001) and a plant‐rich low‐carbohydrate diet (HR 0.73; P_trend <.0001) had a significantly lower risk for all-cause mortality.

Study details: Findings are from an analysis of two ongoing cohort studies, the Nurses’ Health Study (NHS) and NHS II, including 9621 women with stages I-III BC, of which 1269 women died from BC.

Disclosures: This study was sponsored by the US National Institutes of Health and University of Toronto. Two authors declared being the founder of or receiving personal fees, nonfinancial support, and grants from various sources. The other authors declared no conflicts of interest.

Source: Farvid MS et al. Associations of low-carbohydrate diets with breast cancer survival. Cancer. 2023 (Jun 10). Doi: 10.1002/cncr.34819

Key clinical point: The level of stromal tumor-infiltrating lymphocytes (TIL) can provide insights on disease-free survival (DFS) outcomes in human epidermal growth factor receptor 2-low-positive (HER2-low+) early-stage breast cancer (BC).

Major finding: High (>10%) vs low (≤10%) TIL levels were associated with a 53% improvement in DFS in HER2-low+ BC (hazard ratio [HR] 0.47; P = .035) and 58% improvement in DFS in hormone receptor-positive/HER2-low+ BC (HR 0.42; P = .032).

Study details: Findings are from a single-institution retrospective analysis including 1763 patients with early-stage BC who underwent surgery, of whom 429 patients were HER2+, 739 were HER2-low+, and 595 were HER2-0.

Disclosures: This study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The authors declared no conflicts of interest.

Source: Sun T et al. Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: A large cohort retrospective study. Front Oncol. 2023;13:1148228 (Jun 20). Doi: 10.3389/fonc.2023.1148228

Key clinical point: The level of stromal tumor-infiltrating lymphocytes (TIL) can provide insights on disease-free survival (DFS) outcomes in human epidermal growth factor receptor 2-low-positive (HER2-low+) early-stage breast cancer (BC).

Major finding: High (>10%) vs low (≤10%) TIL levels were associated with a 53% improvement in DFS in HER2-low+ BC (hazard ratio [HR] 0.47; P = .035) and 58% improvement in DFS in hormone receptor-positive/HER2-low+ BC (HR 0.42; P = .032).

Study details: Findings are from a single-institution retrospective analysis including 1763 patients with early-stage BC who underwent surgery, of whom 429 patients were HER2+, 739 were HER2-low+, and 595 were HER2-0.

Disclosures: This study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The authors declared no conflicts of interest.

Source: Sun T et al. Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: A large cohort retrospective study. Front Oncol. 2023;13:1148228 (Jun 20). Doi: 10.3389/fonc.2023.1148228

Key clinical point: The level of stromal tumor-infiltrating lymphocytes (TIL) can provide insights on disease-free survival (DFS) outcomes in human epidermal growth factor receptor 2-low-positive (HER2-low+) early-stage breast cancer (BC).

Major finding: High (>10%) vs low (≤10%) TIL levels were associated with a 53% improvement in DFS in HER2-low+ BC (hazard ratio [HR] 0.47; P = .035) and 58% improvement in DFS in hormone receptor-positive/HER2-low+ BC (HR 0.42; P = .032).

Study details: Findings are from a single-institution retrospective analysis including 1763 patients with early-stage BC who underwent surgery, of whom 429 patients were HER2+, 739 were HER2-low+, and 595 were HER2-0.

Disclosures: This study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Shandong Province. The authors declared no conflicts of interest.

Source: Sun T et al. Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: A large cohort retrospective study. Front Oncol. 2023;13:1148228 (Jun 20). Doi: 10.3389/fonc.2023.1148228

Key clinical point: High cardiorespiratory fitness (CRF) may prevent the development of breast cancer (BC) in postmenopausal women.

Major finding: Compared with women with low-to-moderate estimated CRF, those with high eCRF had 24% lower odds of developing BC (adjusted subdistribution hazard ratio 0.76; 95% CI 0.60-0.97).

Study details: This study used the UK Biobank data to evaluate 17,840 post-menopausal women who were free of cancer and were followed for 11 years, of which 529 women developed BC.

Disclosures: This project was funded in part by the Canadian Institutes of Health Research and discretionary funds held by JD Brooks. The authors declared no conflicts of interest.

Source: Christensen RAG et al. Association between estimated cardiorespiratory fitness and breast cancer: A prospective cohort study. Br J Sports Med. 2023 (Jun 19). Doi: 10.1136/bjsports-2021-104870

Key clinical point: High cardiorespiratory fitness (CRF) may prevent the development of breast cancer (BC) in postmenopausal women.

Major finding: Compared with women with low-to-moderate estimated CRF, those with high eCRF had 24% lower odds of developing BC (adjusted subdistribution hazard ratio 0.76; 95% CI 0.60-0.97).

Study details: This study used the UK Biobank data to evaluate 17,840 post-menopausal women who were free of cancer and were followed for 11 years, of which 529 women developed BC.

Disclosures: This project was funded in part by the Canadian Institutes of Health Research and discretionary funds held by JD Brooks. The authors declared no conflicts of interest.

Source: Christensen RAG et al. Association between estimated cardiorespiratory fitness and breast cancer: A prospective cohort study. Br J Sports Med. 2023 (Jun 19). Doi: 10.1136/bjsports-2021-104870

Key clinical point: High cardiorespiratory fitness (CRF) may prevent the development of breast cancer (BC) in postmenopausal women.

Major finding: Compared with women with low-to-moderate estimated CRF, those with high eCRF had 24% lower odds of developing BC (adjusted subdistribution hazard ratio 0.76; 95% CI 0.60-0.97).

Study details: This study used the UK Biobank data to evaluate 17,840 post-menopausal women who were free of cancer and were followed for 11 years, of which 529 women developed BC.

Disclosures: This project was funded in part by the Canadian Institutes of Health Research and discretionary funds held by JD Brooks. The authors declared no conflicts of interest.

Source: Christensen RAG et al. Association between estimated cardiorespiratory fitness and breast cancer: A prospective cohort study. Br J Sports Med. 2023 (Jun 19). Doi: 10.1136/bjsports-2021-104870

Key clinical point: Breast-conserving surgery (BCS) led to similar overall survival (OS) and better disease-specific survival (DSS) outcomes compared with mastectomy in patients with stage I/II adenoid cystic carcinoma of the breast (BACC).

Major finding: The 10-year OS rates were comparable between the BCS and mastectomy groups (P = .968), whereas DSS was significantly improved in patients who underwent BCS vs mastectomy (95% vs 89%; P = .002).

Study details: Findings are from an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) including 583 patients with stage I/II BACC, of whom 386 patients underwent BCS and 197 patients underwent mastectomy.

Disclosures: This study was supported by various grants from the Science and Technology Department of Henan Province, China. The authors declared no conflicts of interest.

Source: Huang T et al. Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast. Sci Rep. 2023;13:10222 (Jun 23). Doi: 10.1038/s41598-023-36644-w

Key clinical point: Breast-conserving surgery (BCS) led to similar overall survival (OS) and better disease-specific survival (DSS) outcomes compared with mastectomy in patients with stage I/II adenoid cystic carcinoma of the breast (BACC).

Major finding: The 10-year OS rates were comparable between the BCS and mastectomy groups (P = .968), whereas DSS was significantly improved in patients who underwent BCS vs mastectomy (95% vs 89%; P = .002).

Study details: Findings are from an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) including 583 patients with stage I/II BACC, of whom 386 patients underwent BCS and 197 patients underwent mastectomy.

Disclosures: This study was supported by various grants from the Science and Technology Department of Henan Province, China. The authors declared no conflicts of interest.

Source: Huang T et al. Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast. Sci Rep. 2023;13:10222 (Jun 23). Doi: 10.1038/s41598-023-36644-w

Key clinical point: Breast-conserving surgery (BCS) led to similar overall survival (OS) and better disease-specific survival (DSS) outcomes compared with mastectomy in patients with stage I/II adenoid cystic carcinoma of the breast (BACC).

Major finding: The 10-year OS rates were comparable between the BCS and mastectomy groups (P = .968), whereas DSS was significantly improved in patients who underwent BCS vs mastectomy (95% vs 89%; P = .002).

Study details: Findings are from an analysis of the Surveillance, Epidemiology, and End Results Program (SEER) including 583 patients with stage I/II BACC, of whom 386 patients underwent BCS and 197 patients underwent mastectomy.

Disclosures: This study was supported by various grants from the Science and Technology Department of Henan Province, China. The authors declared no conflicts of interest.

Source: Huang T et al. Optimal surgical procedure for treating early-stage adenoid cystic carcinoma of the breast. Sci Rep. 2023;13:10222 (Jun 23). Doi: 10.1038/s41598-023-36644-w

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Noninvasive auricular vagus nerve stimulation (VNS) is no more effective than placebo at controlling symptoms of rheumatoid arthritis, according to a new study. But experts emphasize that these results do not mean trials of different forms of VNS will have the same fate.

VNS offers a potential additional therapy for autoimmune disease beyond disease-modifying antirheumatic drugs, explained first author Matthew Baker, MD, clinical chief, division of immunology and rheumatology, Stanford (Calif.) University, and colleagues.

“The principle of VNS is based upon the inflammatory reflex, which describes a primitive connection between the nervous system and immune system,” the authors write. Signals sent down the vagus nerve to the splenic nerve stimulate immune cells in the spleen, which ultimately results in blocking production of inflammatory cytokines such as tumor necrosis factor. “It is hypothesized that this reduction in systemic inflammation can be harnessed for the treatment of diseases such as RA,” they continue, and smaller studies suggest this treatment could benefit patients.

In a previous 12-week, open-label trial, 17 patients with RA who were implanted with a VNS device on the left cervical vagus nerve saw improvement in RA symptoms, as well as a decrease in TNF production. Noninvasive devices that stimulate the auricular branch of the vagus nerve have also shown some promise. A sham-controlled study of 18 patients with systemic lupus erythematosus (SLE) found that patients who received transcutaneous auricular VNS reported reduced musculoskeletal pain over just 4 days. An open-label study of 30 patients with RA showed clinically significant reductions in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) and clinical improvement in American College of Rheumatology responses over 12 weeks. Additional trials have also demonstrated this positive effect of noninvasive VNS on RA symptoms, but all studies conducted thus far have been relatively small or uncontrolled, Dr. Baker said.
 

Results of latest trial

In this new trial, published online in Arthritis & Rheumatology, researchers enrolled 113 patients with active RA who had inadequate responses or intolerance to conventional synthetic DMARDs and were naïve to biologic or targeted synthetic DMARDs. All patients were given an auricular vagus nerve stimulator via a custom-molded earpiece that was controlled by a smartphone app. Patients wore the device for 15 minutes each day. When worn and turned on, the device generated electrical signals delivered transcutaneously to the cymba concha, a region of the ear connected to the auricular branch of the vagus nerve. This stimulation is imperceptible to patients, Dr. Baker explained. “For the sham arm, we simply did not turn the device on at all,” he said. A subject in the sham arm would use the same device on a 15-minute timer, but no stimulation was given.

After 12 weeks, researchers found no statistically significant difference between the treatment and sham arms in achieving 20% improvement in ACR response criteria or mean change in DAS28-CRP. A total of 17 patients, including 12 in the treatment arm, reported adverse events during the study, and all events were categorized as mild to moderate.

While the research team was “obviously disappointed” about the results, Dr. Baker said, negative findings in trials also are important. “The real value of our study is pointing out the need for large controlled, sham-controlled studies,” he said, especially for potential treatments with a lot of enthusiasm behind them.
 

Results don’t seal the fate of other VNS approaches

“As a properly controlled trial, the results are impressively negative,” writes Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, and codirector, Metroplex Clinical Research Center, both in Dallas, in an editorial about the study. Many of the previous studies looking at this therapy in RA were open label, which could bias the results, he argued. The biggest question, he noted, is if other blinded, sham-controlled trials looking at VNS devices will show similar results.

By itself, this finding does not imply that other VNS devices will be unsuccessful, argued Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson chair in rheumatology, and professor of medicine and population and quantitative health sciences, UMass Chan Medical School and UMass Memorial Medical Center, both in Worcester, Mass. He is also an investigator for the RESET-RA trial, a randomized, sham-controlled trial that will assess the safety and efficacy of an implantable VNS device in an estimated 250 patients with RA. He was not involved with Dr. Baker’s work.

“Auricular VNS is delivered more distally than cervical or splenic nerve stimulation,” Dr. Kay said, and the potential effect of these other forms of VNS may have different outcomes.

Cynthia Aranow, MD, rheumatologist and director of the Clinical Autoimmunity Center of Excellence at Feinstein Institutes for Medical Research, Manhasset, New York, agreed with Dr. Kay, noting that direct VNS stimulation via implantable device and transcutaneous stimulation through the skin are not comparable. She also is unaffiliated with the study.

“This group conducted a well-designed, sham-controlled study of a reasonable number of patients and over a reasonable period of time and observed no significant differences between those participants receiving true and those participants receiving sham stimulation,” she wrote in an email. “However, it’s important to point out that the stimulation settings used in this study were kHz (kilohertz) which is 1,000 times greater than the settings used in multiple other studies in which transauricular VNS has been shown to be clinically effective, including studies in long COVID, tinnitus, SLE, cluster headaches, erosive hand osteoarthritis, pediatric kidney disease, among others,” she said.

The role for VNS treatment, whether direct stimulation via implantable device or transcutaneous, in autoimmune and inflammatory diseases “remains to be determined by future studies,” she said.

The study was funded by Nesos. Dr. Baker received personal fees from Nesos during the study. Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Celltrion Healthcare, and several other pharmaceutical companies. Dr. Aranow reports no relevant financial relationships.

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

Key clinical point: Adherence and persistence to adjuvant hormone therapy was associated with improved survival outcomes in older women with hormone receptor-positive (HR+) breast cancer (BC).

Major finding: The risk for all-cause mortality reduced by 25% in patients with vs without cumulative adherence to hormone therapy (hazard ratio [HR] 0.75; P < .001) and decreased by 11% for every 1-year increase in persistence (HR 0.89; P < .001). Each 1-year increase in persistence to hormone therapy also significantly improved breast cancer-specific mortality (HR 0.63; P < .001).

Study details: Findings are from a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data linked with US Medicare claims that included 25,796 older women with HR+ BC who were ≥66 years old and received adjuvant hormone therapy.

Disclosures: This study was partly supported by a grant from the Lilly Endowment, Inc. The authors declared no conflicts of interest.

Source: Zheng D and Thomas J 3rd. Survival benefits associated with being adherent and having longer persistence to adjuvant hormone therapy across up to five years among U.S. Medicare population with breast cancer. Breast Cancer Res Treat. 2023;201:89-104 (Jun 16). Doi: 10.1007/s10549-023-06992-2

Key clinical point: Adherence and persistence to adjuvant hormone therapy was associated with improved survival outcomes in older women with hormone receptor-positive (HR+) breast cancer (BC).

Major finding: The risk for all-cause mortality reduced by 25% in patients with vs without cumulative adherence to hormone therapy (hazard ratio [HR] 0.75; P < .001) and decreased by 11% for every 1-year increase in persistence (HR 0.89; P < .001). Each 1-year increase in persistence to hormone therapy also significantly improved breast cancer-specific mortality (HR 0.63; P < .001).

Study details: Findings are from a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data linked with US Medicare claims that included 25,796 older women with HR+ BC who were ≥66 years old and received adjuvant hormone therapy.

Disclosures: This study was partly supported by a grant from the Lilly Endowment, Inc. The authors declared no conflicts of interest.

Source: Zheng D and Thomas J 3rd. Survival benefits associated with being adherent and having longer persistence to adjuvant hormone therapy across up to five years among U.S. Medicare population with breast cancer. Breast Cancer Res Treat. 2023;201:89-104 (Jun 16). Doi: 10.1007/s10549-023-06992-2

Key clinical point: Adherence and persistence to adjuvant hormone therapy was associated with improved survival outcomes in older women with hormone receptor-positive (HR+) breast cancer (BC).

Major finding: The risk for all-cause mortality reduced by 25% in patients with vs without cumulative adherence to hormone therapy (hazard ratio [HR] 0.75; P < .001) and decreased by 11% for every 1-year increase in persistence (HR 0.89; P < .001). Each 1-year increase in persistence to hormone therapy also significantly improved breast cancer-specific mortality (HR 0.63; P < .001).

Study details: Findings are from a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) data linked with US Medicare claims that included 25,796 older women with HR+ BC who were ≥66 years old and received adjuvant hormone therapy.

Disclosures: This study was partly supported by a grant from the Lilly Endowment, Inc. The authors declared no conflicts of interest.

Source: Zheng D and Thomas J 3rd. Survival benefits associated with being adherent and having longer persistence to adjuvant hormone therapy across up to five years among U.S. Medicare population with breast cancer. Breast Cancer Res Treat. 2023;201:89-104 (Jun 16). Doi: 10.1007/s10549-023-06992-2

Key clinical point: Although patients with early breast cancer (BC) can undergo immediate breast reconstruction (IBR) after mastectomy, those with invasive BC should be made aware of the possibility of local recurrence (LR) if they have undergone skin- or nipple-sparing mastectomy (SSM/NSM), have not received radiotherapy, or had lymphovascular invasion or cancer at the surgical margin.

Major finding: The rate of 7-year LR was generally low (3.6%) but was higher in invasive vs non-invasive BC (4.3% vs 2.1%; P < .001). SSM/NSM (P < .001), lymphovascular invasion (P = .005), cancer at the surgical margin (P < .001), and no radiotherapy (P = .003) were associated with worse LR rates in invasive BC.

Study details: This retrospective, observational study included 4153 patients with early BC who underwent mastectomy with IBR, of which 2851 and 1272 patients had invasive and non-invasive BC, respectively.

Disclosures: This study was supported by a grant from the scientific committee of the Japanese Breast Cancer Society. The authors declared no conflicts of interest.

Source: Ogiya A et al, on behalf of Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Long-term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases. Ann Surg Oncol. 2023 (Jul 5). Doi: 10.1245/s10434-023-13832-6

Key clinical point: Although patients with early breast cancer (BC) can undergo immediate breast reconstruction (IBR) after mastectomy, those with invasive BC should be made aware of the possibility of local recurrence (LR) if they have undergone skin- or nipple-sparing mastectomy (SSM/NSM), have not received radiotherapy, or had lymphovascular invasion or cancer at the surgical margin.

Major finding: The rate of 7-year LR was generally low (3.6%) but was higher in invasive vs non-invasive BC (4.3% vs 2.1%; P < .001). SSM/NSM (P < .001), lymphovascular invasion (P = .005), cancer at the surgical margin (P < .001), and no radiotherapy (P = .003) were associated with worse LR rates in invasive BC.

Study details: This retrospective, observational study included 4153 patients with early BC who underwent mastectomy with IBR, of which 2851 and 1272 patients had invasive and non-invasive BC, respectively.

Disclosures: This study was supported by a grant from the scientific committee of the Japanese Breast Cancer Society. The authors declared no conflicts of interest.

Source: Ogiya A et al, on behalf of Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Long-term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases. Ann Surg Oncol. 2023 (Jul 5). Doi: 10.1245/s10434-023-13832-6

Key clinical point: Although patients with early breast cancer (BC) can undergo immediate breast reconstruction (IBR) after mastectomy, those with invasive BC should be made aware of the possibility of local recurrence (LR) if they have undergone skin- or nipple-sparing mastectomy (SSM/NSM), have not received radiotherapy, or had lymphovascular invasion or cancer at the surgical margin.

Major finding: The rate of 7-year LR was generally low (3.6%) but was higher in invasive vs non-invasive BC (4.3% vs 2.1%; P < .001). SSM/NSM (P < .001), lymphovascular invasion (P = .005), cancer at the surgical margin (P < .001), and no radiotherapy (P = .003) were associated with worse LR rates in invasive BC.

Study details: This retrospective, observational study included 4153 patients with early BC who underwent mastectomy with IBR, of which 2851 and 1272 patients had invasive and non-invasive BC, respectively.

Disclosures: This study was supported by a grant from the scientific committee of the Japanese Breast Cancer Society. The authors declared no conflicts of interest.

Source: Ogiya A et al, on behalf of Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Long-term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases. Ann Surg Oncol. 2023 (Jul 5). Doi: 10.1245/s10434-023-13832-6

Key clinical point: Invasive lobular carcinoma (ILC), the most common special histological type of breast cancer (BC), had poorer survival outcomes than invasive ductal carcinoma (IDC) and no-lobular special type BC.

Major finding: Patients with ILC vs no-lobular special type BC and IDC had the shortest duration of both disease-free survival (197.2 vs 216.7 and 226.5 months, respectively) and overall survival (209.8 vs 227.9 and 233.2 months, respectively), and ILC vs IDC was associated with significantly worse overall survival (hazard ratio 1.45; P = .045).

Study details: Findings are from a retrospective study including 2157 patients with invasive carcinoma of the breast who were categorized into IDC (n = 1814), ILC (n = 193), and no-lobular special type BC (n = 150).

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

Source: Cosar R et al. Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer. PLoS One. 2023;18(7):e0283445 (Jul 10). Doi: 10.1371/journal.pone.0283445

Key clinical point: Invasive lobular carcinoma (ILC), the most common special histological type of breast cancer (BC), had poorer survival outcomes than invasive ductal carcinoma (IDC) and no-lobular special type BC.

Major finding: Patients with ILC vs no-lobular special type BC and IDC had the shortest duration of both disease-free survival (197.2 vs 216.7 and 226.5 months, respectively) and overall survival (209.8 vs 227.9 and 233.2 months, respectively), and ILC vs IDC was associated with significantly worse overall survival (hazard ratio 1.45; P = .045).

Study details: Findings are from a retrospective study including 2157 patients with invasive carcinoma of the breast who were categorized into IDC (n = 1814), ILC (n = 193), and no-lobular special type BC (n = 150).

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

Source: Cosar R et al. Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer. PLoS One. 2023;18(7):e0283445 (Jul 10). Doi: 10.1371/journal.pone.0283445

Key clinical point: Invasive lobular carcinoma (ILC), the most common special histological type of breast cancer (BC), had poorer survival outcomes than invasive ductal carcinoma (IDC) and no-lobular special type BC.

Major finding: Patients with ILC vs no-lobular special type BC and IDC had the shortest duration of both disease-free survival (197.2 vs 216.7 and 226.5 months, respectively) and overall survival (209.8 vs 227.9 and 233.2 months, respectively), and ILC vs IDC was associated with significantly worse overall survival (hazard ratio 1.45; P = .045).

Study details: Findings are from a retrospective study including 2157 patients with invasive carcinoma of the breast who were categorized into IDC (n = 1814), ILC (n = 193), and no-lobular special type BC (n = 150).

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

Source: Cosar R et al. Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer. PLoS One. 2023;18(7):e0283445 (Jul 10). Doi: 10.1371/journal.pone.0283445