A large brain imaging study of adults with six different psychiatric illnesses shows that heterogeneity in regional gray matter volume deviations is a general feature of psychiatric illness, but that these regionally heterogeneous areas are often embedded within common functional circuits and networks.

The findings suggest that “targeting brain circuits, rather than specific brain regions, may be a more effective way of developing new treatments,” study investigator Ashlea Segal said in an email.

The findings also suggest that it’s “unlikely that a single cause or mechanism of a given disorder exists, and that a ‘one-size-fits-all’ approach to treatment is likely only appropriate for a small subset of individuals. In fact, one size doesn’t fit all. It probably doesn’t even fit most,” said Ms. Segal, a PhD candidate with the Turner Institute for Brain and Mental Health’s Neural Systems and Behaviour Lab at Monash University in Melbourne.

“Focusing on brain alterations at an individual level allows us to develop more personally tailored treatments,” Ms. Segal added.

Regional heterogeneity, the authors write, “thus offers a plausible explanation for the well-described clinical heterogeneity observed in psychiatric disorders, while circuit- and network-level aggregation of deviations is a putative neural substrate for phenotypic similarities between patients assigned the same diagnosis.”

The study was published online in Nature Neuroscience
 

Beyond group averages

For decades, researchers have mapped brain areas showing reduced gray matter volume (GMV) in people diagnosed with a variety of mental illnesses, but these maps have only been generated at the level of group averages, Ms. Segal explained.

“This means that we understand how the brains of people with, say, schizophrenia, differ from those without schizophrenia on average, but we can’t really say much about individual people,” Ms. Segal said.

For their study, the researchers used new statistical techniques developed by Andre Marquand, PhD, who co-led the project, to characterize the heterogeneity of GMV differences in 1,294 individuals diagnosed with one of six psychiatric conditions and 1,465 matched controls. Dr. Marquand is affiliated with the Donders Institute for Brain, Cognition, and Behavior in Nijmegen, the Netherlands.

These techniques “allow us to benchmark the size of over 1,000 different brain regions in any given person relative to what we should expect to see in the general population. In this way, we can identify, for any person, brain regions showing unusually small or large volumes, given that person’s age and sex,” Ms. Segal told this news organization.

The clinical sample included 202 individuals with autism spectrum disorder, 153 with attention-deficit/hyperactivity disorder (ADHD), 228 with bipolar disorder, 161 with major depressive disorder, 167 with obsessive-compulsive disorder, and 383 individuals with schizophrenia.

Confirming earlier findings, those with psychiatric illness showed more GMV deviations than healthy controls, the researchers found.

However, at the individual level, deviations from population expectations for regional gray matter volumes were “highly heterogeneous,” affecting the same area in less than 7% of people with the same diagnosis, they note. “This result means that it is difficult to pinpoint treatment targets or causal mechanisms by focusing on group averages alone,” Alex Fornito, PhD, of Monash University, who led the research team, said in a statement.

“It may also explain why people with the same diagnosis show wide variability in their symptom profiles and treatment outcomes,” Dr. Fornito added.

Yet, despite considerable heterogeneity at the regional level across different diagnoses, these deviations were embedded within common functional circuits and networks in up to 56% of cases. 

The salience-ventral attention network, for example, which plays a central role in cognitive control, interoceptive awareness, and switching between internally and externally focused attention, was implicated across diagnoses, with other neural networks selectively involved in depression, bipolar disorder, schizophrenia, and ADHD.

The researchers say the approach they developed opens new opportunities for mapping brain changes in mental illness.

“The framework we have developed allows us to understand the diversity of brain changes in people with mental illness at different levels, from individual regions through to more widespread brain circuits and networks, offering a deeper insight into how the brain is affected in individual people,” Dr. Fornito said in a statement.

The study had no commercial funding. Ms. Segal, Dr. Fornito, and Dr. Marquand report no relevant financial relationships.

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

A large brain imaging study of adults with six different psychiatric illnesses shows that heterogeneity in regional gray matter volume deviations is a general feature of psychiatric illness, but that these regionally heterogeneous areas are often embedded within common functional circuits and networks.

The findings suggest that “targeting brain circuits, rather than specific brain regions, may be a more effective way of developing new treatments,” study investigator Ashlea Segal said in an email.

The findings also suggest that it’s “unlikely that a single cause or mechanism of a given disorder exists, and that a ‘one-size-fits-all’ approach to treatment is likely only appropriate for a small subset of individuals. In fact, one size doesn’t fit all. It probably doesn’t even fit most,” said Ms. Segal, a PhD candidate with the Turner Institute for Brain and Mental Health’s Neural Systems and Behaviour Lab at Monash University in Melbourne.

“Focusing on brain alterations at an individual level allows us to develop more personally tailored treatments,” Ms. Segal added.

Regional heterogeneity, the authors write, “thus offers a plausible explanation for the well-described clinical heterogeneity observed in psychiatric disorders, while circuit- and network-level aggregation of deviations is a putative neural substrate for phenotypic similarities between patients assigned the same diagnosis.”

The study was published online in Nature Neuroscience
 

Beyond group averages

For decades, researchers have mapped brain areas showing reduced gray matter volume (GMV) in people diagnosed with a variety of mental illnesses, but these maps have only been generated at the level of group averages, Ms. Segal explained.

“This means that we understand how the brains of people with, say, schizophrenia, differ from those without schizophrenia on average, but we can’t really say much about individual people,” Ms. Segal said.

For their study, the researchers used new statistical techniques developed by Andre Marquand, PhD, who co-led the project, to characterize the heterogeneity of GMV differences in 1,294 individuals diagnosed with one of six psychiatric conditions and 1,465 matched controls. Dr. Marquand is affiliated with the Donders Institute for Brain, Cognition, and Behavior in Nijmegen, the Netherlands.

These techniques “allow us to benchmark the size of over 1,000 different brain regions in any given person relative to what we should expect to see in the general population. In this way, we can identify, for any person, brain regions showing unusually small or large volumes, given that person’s age and sex,” Ms. Segal told this news organization.

The clinical sample included 202 individuals with autism spectrum disorder, 153 with attention-deficit/hyperactivity disorder (ADHD), 228 with bipolar disorder, 161 with major depressive disorder, 167 with obsessive-compulsive disorder, and 383 individuals with schizophrenia.

Confirming earlier findings, those with psychiatric illness showed more GMV deviations than healthy controls, the researchers found.

However, at the individual level, deviations from population expectations for regional gray matter volumes were “highly heterogeneous,” affecting the same area in less than 7% of people with the same diagnosis, they note. “This result means that it is difficult to pinpoint treatment targets or causal mechanisms by focusing on group averages alone,” Alex Fornito, PhD, of Monash University, who led the research team, said in a statement.

“It may also explain why people with the same diagnosis show wide variability in their symptom profiles and treatment outcomes,” Dr. Fornito added.

Yet, despite considerable heterogeneity at the regional level across different diagnoses, these deviations were embedded within common functional circuits and networks in up to 56% of cases. 

The salience-ventral attention network, for example, which plays a central role in cognitive control, interoceptive awareness, and switching between internally and externally focused attention, was implicated across diagnoses, with other neural networks selectively involved in depression, bipolar disorder, schizophrenia, and ADHD.

The researchers say the approach they developed opens new opportunities for mapping brain changes in mental illness.

“The framework we have developed allows us to understand the diversity of brain changes in people with mental illness at different levels, from individual regions through to more widespread brain circuits and networks, offering a deeper insight into how the brain is affected in individual people,” Dr. Fornito said in a statement.

The study had no commercial funding. Ms. Segal, Dr. Fornito, and Dr. Marquand report no relevant financial relationships.

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

A large brain imaging study of adults with six different psychiatric illnesses shows that heterogeneity in regional gray matter volume deviations is a general feature of psychiatric illness, but that these regionally heterogeneous areas are often embedded within common functional circuits and networks.

The findings suggest that “targeting brain circuits, rather than specific brain regions, may be a more effective way of developing new treatments,” study investigator Ashlea Segal said in an email.

The findings also suggest that it’s “unlikely that a single cause or mechanism of a given disorder exists, and that a ‘one-size-fits-all’ approach to treatment is likely only appropriate for a small subset of individuals. In fact, one size doesn’t fit all. It probably doesn’t even fit most,” said Ms. Segal, a PhD candidate with the Turner Institute for Brain and Mental Health’s Neural Systems and Behaviour Lab at Monash University in Melbourne.

“Focusing on brain alterations at an individual level allows us to develop more personally tailored treatments,” Ms. Segal added.

Regional heterogeneity, the authors write, “thus offers a plausible explanation for the well-described clinical heterogeneity observed in psychiatric disorders, while circuit- and network-level aggregation of deviations is a putative neural substrate for phenotypic similarities between patients assigned the same diagnosis.”

The study was published online in Nature Neuroscience
 

Beyond group averages

For decades, researchers have mapped brain areas showing reduced gray matter volume (GMV) in people diagnosed with a variety of mental illnesses, but these maps have only been generated at the level of group averages, Ms. Segal explained.

“This means that we understand how the brains of people with, say, schizophrenia, differ from those without schizophrenia on average, but we can’t really say much about individual people,” Ms. Segal said.

For their study, the researchers used new statistical techniques developed by Andre Marquand, PhD, who co-led the project, to characterize the heterogeneity of GMV differences in 1,294 individuals diagnosed with one of six psychiatric conditions and 1,465 matched controls. Dr. Marquand is affiliated with the Donders Institute for Brain, Cognition, and Behavior in Nijmegen, the Netherlands.

These techniques “allow us to benchmark the size of over 1,000 different brain regions in any given person relative to what we should expect to see in the general population. In this way, we can identify, for any person, brain regions showing unusually small or large volumes, given that person’s age and sex,” Ms. Segal told this news organization.

The clinical sample included 202 individuals with autism spectrum disorder, 153 with attention-deficit/hyperactivity disorder (ADHD), 228 with bipolar disorder, 161 with major depressive disorder, 167 with obsessive-compulsive disorder, and 383 individuals with schizophrenia.

Confirming earlier findings, those with psychiatric illness showed more GMV deviations than healthy controls, the researchers found.

However, at the individual level, deviations from population expectations for regional gray matter volumes were “highly heterogeneous,” affecting the same area in less than 7% of people with the same diagnosis, they note. “This result means that it is difficult to pinpoint treatment targets or causal mechanisms by focusing on group averages alone,” Alex Fornito, PhD, of Monash University, who led the research team, said in a statement.

“It may also explain why people with the same diagnosis show wide variability in their symptom profiles and treatment outcomes,” Dr. Fornito added.

Yet, despite considerable heterogeneity at the regional level across different diagnoses, these deviations were embedded within common functional circuits and networks in up to 56% of cases. 

The salience-ventral attention network, for example, which plays a central role in cognitive control, interoceptive awareness, and switching between internally and externally focused attention, was implicated across diagnoses, with other neural networks selectively involved in depression, bipolar disorder, schizophrenia, and ADHD.

The researchers say the approach they developed opens new opportunities for mapping brain changes in mental illness.

“The framework we have developed allows us to understand the diversity of brain changes in people with mental illness at different levels, from individual regions through to more widespread brain circuits and networks, offering a deeper insight into how the brain is affected in individual people,” Dr. Fornito said in a statement.

The study had no commercial funding. Ms. Segal, Dr. Fornito, and Dr. Marquand report no relevant financial relationships.

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

Key clinical point: Association of body mass index (BMI) with cardiometabolic risk score (CRS) and obesity-related protein score (OPS) and the relation between CRS and OPS in postmenopausal women indicated that weight control for the reduction of cardiometabolic risks may also help prevent breast cancer (BC).

Major finding: A 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 units; P = .025) and postmenopausal women (0.054 units; P = .033) and increased OPS by 0.588 units (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in post-menopausal women (β 0.281, P = .034).

Study details: This longitudinal study included 444 healthy women age 35-64 years.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Xu B et al. Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort. Sci Rep. 2023;13:12361 (Jul 31). doi: 10.1038/s41598-023-39387-w

Key clinical point: Association of body mass index (BMI) with cardiometabolic risk score (CRS) and obesity-related protein score (OPS) and the relation between CRS and OPS in postmenopausal women indicated that weight control for the reduction of cardiometabolic risks may also help prevent breast cancer (BC).

Major finding: A 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 units; P = .025) and postmenopausal women (0.054 units; P = .033) and increased OPS by 0.588 units (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in post-menopausal women (β 0.281, P = .034).

Study details: This longitudinal study included 444 healthy women age 35-64 years.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Xu B et al. Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort. Sci Rep. 2023;13:12361 (Jul 31). doi: 10.1038/s41598-023-39387-w

Key clinical point: Association of body mass index (BMI) with cardiometabolic risk score (CRS) and obesity-related protein score (OPS) and the relation between CRS and OPS in postmenopausal women indicated that weight control for the reduction of cardiometabolic risks may also help prevent breast cancer (BC).

Major finding: A 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 units; P = .025) and postmenopausal women (0.054 units; P = .033) and increased OPS by 0.588 units (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in post-menopausal women (β 0.281, P = .034).

Study details: This longitudinal study included 444 healthy women age 35-64 years.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Xu B et al. Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort. Sci Rep. 2023;13:12361 (Jul 31). doi: 10.1038/s41598-023-39387-w

Key clinical point: Women, particularly post-menopausal women, with diabetes mellitus (DM) faced a higher risk of developing different subtypes of breast cancer (BC).

Major finding: Women with DM had a 20% greater risk of developing BC (risk ratio [RR] 1.20; 95% CI 1.11-1.29), with the risk persisting only in postmenopausal women (RR 1.12; 95% CI 1.07-1.17). The risk of estrogen receptor-negative BC (RR 1.16; 95% CI 1.04-1.30) and triple-negative BC (RR 1.41; 95% CI 1.01-1.96) subtypes increased in patients with DM.

Study details: This meta-analysis of 70 cohort and case-control studies included premenopausal and postmenopausal women with or without DM who developed BC.

Disclosures: JM Chan received funding from the Cancer League Foundation. RE Graff, the corresponding author, declared being supported by a Young Investigator Award from the Prostate Cancer Foundation.

Source: Xiong F et al. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023;e3709 (Aug 7). doi: 10.1002/dmrr.3709

Key clinical point: Women, particularly post-menopausal women, with diabetes mellitus (DM) faced a higher risk of developing different subtypes of breast cancer (BC).

Major finding: Women with DM had a 20% greater risk of developing BC (risk ratio [RR] 1.20; 95% CI 1.11-1.29), with the risk persisting only in postmenopausal women (RR 1.12; 95% CI 1.07-1.17). The risk of estrogen receptor-negative BC (RR 1.16; 95% CI 1.04-1.30) and triple-negative BC (RR 1.41; 95% CI 1.01-1.96) subtypes increased in patients with DM.

Study details: This meta-analysis of 70 cohort and case-control studies included premenopausal and postmenopausal women with or without DM who developed BC.

Disclosures: JM Chan received funding from the Cancer League Foundation. RE Graff, the corresponding author, declared being supported by a Young Investigator Award from the Prostate Cancer Foundation.

Source: Xiong F et al. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023;e3709 (Aug 7). doi: 10.1002/dmrr.3709

Key clinical point: Women, particularly post-menopausal women, with diabetes mellitus (DM) faced a higher risk of developing different subtypes of breast cancer (BC).

Major finding: Women with DM had a 20% greater risk of developing BC (risk ratio [RR] 1.20; 95% CI 1.11-1.29), with the risk persisting only in postmenopausal women (RR 1.12; 95% CI 1.07-1.17). The risk of estrogen receptor-negative BC (RR 1.16; 95% CI 1.04-1.30) and triple-negative BC (RR 1.41; 95% CI 1.01-1.96) subtypes increased in patients with DM.

Study details: This meta-analysis of 70 cohort and case-control studies included premenopausal and postmenopausal women with or without DM who developed BC.

Disclosures: JM Chan received funding from the Cancer League Foundation. RE Graff, the corresponding author, declared being supported by a Young Investigator Award from the Prostate Cancer Foundation.

Source: Xiong F et al. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023;e3709 (Aug 7). doi: 10.1002/dmrr.3709

Key clinical point: Use of metformin reduced the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer (BC).

Major finding: A significantly lower proportion of patients receiving metformin vs placebo had grade 2 paclitaxel-induced peripheral neuropathy (36.1% vs 67.6%; P = .007).

Study details: This parallel-group trial included 73 patients with BC who were randomly assigned to receive either metformin or placebo 1 week before initiating treatment with paclitaxel.

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

Source: Bakry HM et al. Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled trial. Front Pharmacol. 2023;14:1181312 (Jul 31). doi: 10.3389/fphar.2023.1181312

Key clinical point: Use of metformin reduced the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer (BC).

Major finding: A significantly lower proportion of patients receiving metformin vs placebo had grade 2 paclitaxel-induced peripheral neuropathy (36.1% vs 67.6%; P = .007).

Study details: This parallel-group trial included 73 patients with BC who were randomly assigned to receive either metformin or placebo 1 week before initiating treatment with paclitaxel.

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

Source: Bakry HM et al. Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled trial. Front Pharmacol. 2023;14:1181312 (Jul 31). doi: 10.3389/fphar.2023.1181312

Key clinical point: Use of metformin reduced the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer (BC).

Major finding: A significantly lower proportion of patients receiving metformin vs placebo had grade 2 paclitaxel-induced peripheral neuropathy (36.1% vs 67.6%; P = .007).

Study details: This parallel-group trial included 73 patients with BC who were randomly assigned to receive either metformin or placebo 1 week before initiating treatment with paclitaxel.

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

Source: Bakry HM et al. Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled trial. Front Pharmacol. 2023;14:1181312 (Jul 31). doi: 10.3389/fphar.2023.1181312

Key clinical point: In postmenopausal women with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-positive (HER2+) advanced or metastatic breast cancer (BC), 500 mg fulvestrant (F500) with or without anti-HER2 therapy prolonged the time to treatment failure (TTF) in first- and second-line settings and improved the overall survival (OS) outcomes in those who received chemotherapy-free initial systemic therapy and required longer time to chemotherapy (TTC).

Major finding: F500 improved TTF in the first- and second-line vs third- or later-lines of therapy (6.6 vs 3.7 months; P = .014) and OS in patients who received chemotherapy-free initial systemic therapy and had TTC ≥ 3 years vs < 3 years (hazard ratio 0.32; P = .001).

Study details: This study analyzed 94 postmenopausal women with ER+/HER2+ advanced or metastatic BC from the SAFARI study who received F500 with or without anti-HER2 therapy.

Disclosures: This study was sponsored by Japan Breast Cancer Research Group and AstraZeneca. Several authors declared ties with various sources, including the funding agencies.

Source: Masuyama M et al. Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06). Cancer Med. 2023 (Aug 1). doi: 10.1002/cam4.6390

Key clinical point: In postmenopausal women with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-positive (HER2+) advanced or metastatic breast cancer (BC), 500 mg fulvestrant (F500) with or without anti-HER2 therapy prolonged the time to treatment failure (TTF) in first- and second-line settings and improved the overall survival (OS) outcomes in those who received chemotherapy-free initial systemic therapy and required longer time to chemotherapy (TTC).

Major finding: F500 improved TTF in the first- and second-line vs third- or later-lines of therapy (6.6 vs 3.7 months; P = .014) and OS in patients who received chemotherapy-free initial systemic therapy and had TTC ≥ 3 years vs < 3 years (hazard ratio 0.32; P = .001).

Study details: This study analyzed 94 postmenopausal women with ER+/HER2+ advanced or metastatic BC from the SAFARI study who received F500 with or without anti-HER2 therapy.

Disclosures: This study was sponsored by Japan Breast Cancer Research Group and AstraZeneca. Several authors declared ties with various sources, including the funding agencies.

Source: Masuyama M et al. Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06). Cancer Med. 2023 (Aug 1). doi: 10.1002/cam4.6390

Key clinical point: In postmenopausal women with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-positive (HER2+) advanced or metastatic breast cancer (BC), 500 mg fulvestrant (F500) with or without anti-HER2 therapy prolonged the time to treatment failure (TTF) in first- and second-line settings and improved the overall survival (OS) outcomes in those who received chemotherapy-free initial systemic therapy and required longer time to chemotherapy (TTC).

Major finding: F500 improved TTF in the first- and second-line vs third- or later-lines of therapy (6.6 vs 3.7 months; P = .014) and OS in patients who received chemotherapy-free initial systemic therapy and had TTC ≥ 3 years vs < 3 years (hazard ratio 0.32; P = .001).

Study details: This study analyzed 94 postmenopausal women with ER+/HER2+ advanced or metastatic BC from the SAFARI study who received F500 with or without anti-HER2 therapy.

Disclosures: This study was sponsored by Japan Breast Cancer Research Group and AstraZeneca. Several authors declared ties with various sources, including the funding agencies.

Source: Masuyama M et al. Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06). Cancer Med. 2023 (Aug 1). doi: 10.1002/cam4.6390

Key clinical point: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) improved survival outcomes in women age ≥ 70 years with T1-2N0 estrogen receptor-negative (ER−) breast cancer (BC); however, patients age ≥ 80 years or those with T1mic+T1a, T1b tumors did not benefit from it.

Major finding: Overall survival (hazard ratio [HR] 0.62; P < .001) and BC-specific survival (HR 0.71; P = .002) improved significantly in patients who received vs did not receive adjuvant RT. Patients age ≥ 80 years (P = .056) or with clinical stage T1mic+T1a (P = .543) or T1b (P = .329) tumors did not show improvement in OS after receiving RT.

Study details: This study included 4201 women with T1-2N0 ER− BC (from the Surveillance, Epidemiology, and End Results [SEER] study) who were age ≥ 70 years and underwent BCS, of which 2811 women received adjuvant RT.

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

Source: Chen C et al. The effect of adjuvant radiotherapy after breast-conserving surgery in elderly women with T1-2N0 estrogen receptor-negative breast cancer. PLoS One. 2023;18(8):e0288078 (Aug 3). doi: 10.1371/journal.pone.0288078

Key clinical point: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) improved survival outcomes in women age ≥ 70 years with T1-2N0 estrogen receptor-negative (ER−) breast cancer (BC); however, patients age ≥ 80 years or those with T1mic+T1a, T1b tumors did not benefit from it.

Major finding: Overall survival (hazard ratio [HR] 0.62; P < .001) and BC-specific survival (HR 0.71; P = .002) improved significantly in patients who received vs did not receive adjuvant RT. Patients age ≥ 80 years (P = .056) or with clinical stage T1mic+T1a (P = .543) or T1b (P = .329) tumors did not show improvement in OS after receiving RT.

Study details: This study included 4201 women with T1-2N0 ER− BC (from the Surveillance, Epidemiology, and End Results [SEER] study) who were age ≥ 70 years and underwent BCS, of which 2811 women received adjuvant RT.

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

Source: Chen C et al. The effect of adjuvant radiotherapy after breast-conserving surgery in elderly women with T1-2N0 estrogen receptor-negative breast cancer. PLoS One. 2023;18(8):e0288078 (Aug 3). doi: 10.1371/journal.pone.0288078

Key clinical point: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) improved survival outcomes in women age ≥ 70 years with T1-2N0 estrogen receptor-negative (ER−) breast cancer (BC); however, patients age ≥ 80 years or those with T1mic+T1a, T1b tumors did not benefit from it.

Major finding: Overall survival (hazard ratio [HR] 0.62; P < .001) and BC-specific survival (HR 0.71; P = .002) improved significantly in patients who received vs did not receive adjuvant RT. Patients age ≥ 80 years (P = .056) or with clinical stage T1mic+T1a (P = .543) or T1b (P = .329) tumors did not show improvement in OS after receiving RT.

Study details: This study included 4201 women with T1-2N0 ER− BC (from the Surveillance, Epidemiology, and End Results [SEER] study) who were age ≥ 70 years and underwent BCS, of which 2811 women received adjuvant RT.

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

Source: Chen C et al. The effect of adjuvant radiotherapy after breast-conserving surgery in elderly women with T1-2N0 estrogen receptor-negative breast cancer. PLoS One. 2023;18(8):e0288078 (Aug 3). doi: 10.1371/journal.pone.0288078

Key clinical point: Decreased levels of plasma apolipoprotein M (APOM) were associated with worsened mortality outcomes in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2 negative (HER2−) metastatic breast cancer (BC).

Major finding: Mean baseline plasma APOM levels were significantly lower in patients who had deceased vs survived during the 24-month follow-up period (42.7 vs 52.2 µg/mL; P = .003), and the doubling of plasma APOM levels was associated with an improvement in the overall survival outcomes (adjusted hazard ratio 0.23; P = .001).

Study details: This study measured APOM plasma levels in 75 patients with ER+/HER2− metastatic BC.

Disclosures: This study was partly sponsored by the European Regional Development fund. The authors declared no conflicts of interest.

Source: Muendlein A et al. Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients. Breast Cancer Res Treat. 2023 (Jul 25). doi: 10.1007/s10549-023-07045-4

Key clinical point: Decreased levels of plasma apolipoprotein M (APOM) were associated with worsened mortality outcomes in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2 negative (HER2−) metastatic breast cancer (BC).

Major finding: Mean baseline plasma APOM levels were significantly lower in patients who had deceased vs survived during the 24-month follow-up period (42.7 vs 52.2 µg/mL; P = .003), and the doubling of plasma APOM levels was associated with an improvement in the overall survival outcomes (adjusted hazard ratio 0.23; P = .001).

Study details: This study measured APOM plasma levels in 75 patients with ER+/HER2− metastatic BC.

Disclosures: This study was partly sponsored by the European Regional Development fund. The authors declared no conflicts of interest.

Source: Muendlein A et al. Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients. Breast Cancer Res Treat. 2023 (Jul 25). doi: 10.1007/s10549-023-07045-4

Key clinical point: Decreased levels of plasma apolipoprotein M (APOM) were associated with worsened mortality outcomes in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2 negative (HER2−) metastatic breast cancer (BC).

Major finding: Mean baseline plasma APOM levels were significantly lower in patients who had deceased vs survived during the 24-month follow-up period (42.7 vs 52.2 µg/mL; P = .003), and the doubling of plasma APOM levels was associated with an improvement in the overall survival outcomes (adjusted hazard ratio 0.23; P = .001).

Study details: This study measured APOM plasma levels in 75 patients with ER+/HER2− metastatic BC.

Disclosures: This study was partly sponsored by the European Regional Development fund. The authors declared no conflicts of interest.

Source: Muendlein A et al. Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients. Breast Cancer Res Treat. 2023 (Jul 25). doi: 10.1007/s10549-023-07045-4

Key clinical point: Omission of axillary lymph node dissection (ALND) was associated with lymph node understaging but had no impact on systemic therapy recommendations in patients with clinically node-positive breast cancer (cN+ BC).

Major finding: A higher proportion of patients undergoing ALND vs receiving axillary radiotherapy (ART) were detected with ≥ 4 positive nodes (58.9% vs 33.8%). ALND was not associated with the proportion of patients receiving adjuvant chemotherapy after upfront surgery (adjusted odds ratio [aOR] 0.72; 95% CI 0.19-2.67) or systemic therapy after neoadjuvant chemotherapy (aOR 0.86; 95% CI 0.43-1.70).

Study details: Findings are from a prospective, observational cohort study including 500 patients with cN+ BC who underwent tailored axillary surgery and were randomly assigned to undergo ALND or receive ART.

Disclosures: This study was supported by the Swiss State Secretariat for Education, Research and Innovation, and other sources. Some authors declared receiving grants, personal fees, speaker fees, patient fees or having other ties with various sources including the funding source.

Source: Weber WP et al and the TAXIS Study Writing Group . Association of axillary dissection with systemic therapy in patients with clinically node-positive breast cancer. JAMA Surg. 2023 (Jul 19). doi: 10.1001/jamasurg.2023.2840

Key clinical point: Omission of axillary lymph node dissection (ALND) was associated with lymph node understaging but had no impact on systemic therapy recommendations in patients with clinically node-positive breast cancer (cN+ BC).

Major finding: A higher proportion of patients undergoing ALND vs receiving axillary radiotherapy (ART) were detected with ≥ 4 positive nodes (58.9% vs 33.8%). ALND was not associated with the proportion of patients receiving adjuvant chemotherapy after upfront surgery (adjusted odds ratio [aOR] 0.72; 95% CI 0.19-2.67) or systemic therapy after neoadjuvant chemotherapy (aOR 0.86; 95% CI 0.43-1.70).

Study details: Findings are from a prospective, observational cohort study including 500 patients with cN+ BC who underwent tailored axillary surgery and were randomly assigned to undergo ALND or receive ART.

Disclosures: This study was supported by the Swiss State Secretariat for Education, Research and Innovation, and other sources. Some authors declared receiving grants, personal fees, speaker fees, patient fees or having other ties with various sources including the funding source.

Source: Weber WP et al and the TAXIS Study Writing Group . Association of axillary dissection with systemic therapy in patients with clinically node-positive breast cancer. JAMA Surg. 2023 (Jul 19). doi: 10.1001/jamasurg.2023.2840

Key clinical point: Omission of axillary lymph node dissection (ALND) was associated with lymph node understaging but had no impact on systemic therapy recommendations in patients with clinically node-positive breast cancer (cN+ BC).

Major finding: A higher proportion of patients undergoing ALND vs receiving axillary radiotherapy (ART) were detected with ≥ 4 positive nodes (58.9% vs 33.8%). ALND was not associated with the proportion of patients receiving adjuvant chemotherapy after upfront surgery (adjusted odds ratio [aOR] 0.72; 95% CI 0.19-2.67) or systemic therapy after neoadjuvant chemotherapy (aOR 0.86; 95% CI 0.43-1.70).

Study details: Findings are from a prospective, observational cohort study including 500 patients with cN+ BC who underwent tailored axillary surgery and were randomly assigned to undergo ALND or receive ART.

Disclosures: This study was supported by the Swiss State Secretariat for Education, Research and Innovation, and other sources. Some authors declared receiving grants, personal fees, speaker fees, patient fees or having other ties with various sources including the funding source.

Source: Weber WP et al and the TAXIS Study Writing Group . Association of axillary dissection with systemic therapy in patients with clinically node-positive breast cancer. JAMA Surg. 2023 (Jul 19). doi: 10.1001/jamasurg.2023.2840

Key clinical point: Patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) advanced breast cancer (BC) reported greater clinical benefits with oral vinorelbine + cyclophosphamide + capecitabine (VEX) regimen vs intravenous paclitaxel without experiencing unmanageable adverse events (AE).

Major finding: Oral metronomic VEX vs intravenous paclitaxel significantly improved the median time to treatment failure (8.3 vs 5.7 months; hazard ratio [HR] 0.61; P = .008) and median progression-free survival (11.1 vs 6.9 months; HR 0.67; P = .03). Although the frequency of targeted grade 3 or 4 AE was higher in the VEX vs paclitaxel group (42.9% vs 28.6%), they were mostly manageable.

Study details: Findings are from the phase 2 METEORA-II study including 140 patients with ER+/ERBB2− metastatic BC who were treated with ≥ 1 line of chemotherapy and were randomly assigned to receive oral VEX or weekly intravenous paclitaxel in 4-week cycles.

Disclosures: This study was funded by Pierre-Fabre Pharma Srl and other sources. Some authors declared receiving grants, personal fees, consulting fees, funding, speaker honoraria, and having other ties with various sources, including the funding agencies.

Source: Munzone E et al for the International Breast Cancer Study Group (IBCSG). Efficacy of metronomic oral vinorelbine, cyclophosphamide, and capecitabine vs weekly intravenous paclitaxel in patients with estrogen receptor-positive, ERBB2-negative metastatic breast cancer: Final results from the phase 2 METEORA-II randomized clinical trial. JAMA Oncol. 2023 (Jul 13). doi: 10.1001/jamaoncol.2023.2150

Key clinical point: Patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) advanced breast cancer (BC) reported greater clinical benefits with oral vinorelbine + cyclophosphamide + capecitabine (VEX) regimen vs intravenous paclitaxel without experiencing unmanageable adverse events (AE).

Major finding: Oral metronomic VEX vs intravenous paclitaxel significantly improved the median time to treatment failure (8.3 vs 5.7 months; hazard ratio [HR] 0.61; P = .008) and median progression-free survival (11.1 vs 6.9 months; HR 0.67; P = .03). Although the frequency of targeted grade 3 or 4 AE was higher in the VEX vs paclitaxel group (42.9% vs 28.6%), they were mostly manageable.

Study details: Findings are from the phase 2 METEORA-II study including 140 patients with ER+/ERBB2− metastatic BC who were treated with ≥ 1 line of chemotherapy and were randomly assigned to receive oral VEX or weekly intravenous paclitaxel in 4-week cycles.

Disclosures: This study was funded by Pierre-Fabre Pharma Srl and other sources. Some authors declared receiving grants, personal fees, consulting fees, funding, speaker honoraria, and having other ties with various sources, including the funding agencies.

Source: Munzone E et al for the International Breast Cancer Study Group (IBCSG). Efficacy of metronomic oral vinorelbine, cyclophosphamide, and capecitabine vs weekly intravenous paclitaxel in patients with estrogen receptor-positive, ERBB2-negative metastatic breast cancer: Final results from the phase 2 METEORA-II randomized clinical trial. JAMA Oncol. 2023 (Jul 13). doi: 10.1001/jamaoncol.2023.2150

Key clinical point: Patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) advanced breast cancer (BC) reported greater clinical benefits with oral vinorelbine + cyclophosphamide + capecitabine (VEX) regimen vs intravenous paclitaxel without experiencing unmanageable adverse events (AE).

Major finding: Oral metronomic VEX vs intravenous paclitaxel significantly improved the median time to treatment failure (8.3 vs 5.7 months; hazard ratio [HR] 0.61; P = .008) and median progression-free survival (11.1 vs 6.9 months; HR 0.67; P = .03). Although the frequency of targeted grade 3 or 4 AE was higher in the VEX vs paclitaxel group (42.9% vs 28.6%), they were mostly manageable.

Study details: Findings are from the phase 2 METEORA-II study including 140 patients with ER+/ERBB2− metastatic BC who were treated with ≥ 1 line of chemotherapy and were randomly assigned to receive oral VEX or weekly intravenous paclitaxel in 4-week cycles.

Disclosures: This study was funded by Pierre-Fabre Pharma Srl and other sources. Some authors declared receiving grants, personal fees, consulting fees, funding, speaker honoraria, and having other ties with various sources, including the funding agencies.

Source: Munzone E et al for the International Breast Cancer Study Group (IBCSG). Efficacy of metronomic oral vinorelbine, cyclophosphamide, and capecitabine vs weekly intravenous paclitaxel in patients with estrogen receptor-positive, ERBB2-negative metastatic breast cancer: Final results from the phase 2 METEORA-II randomized clinical trial. JAMA Oncol. 2023 (Jul 13). doi: 10.1001/jamaoncol.2023.2150

Key clinical point: Biological aging was faster in women who were diagnosed and treated for breast cancer (BC) vs women who remained free of BC.

Major finding: Women who were diagnosed and treated for BC had higher epigenetic age acceleration metrics (PhenoAge epigenetic clock: standardized mean difference [β] 0.13; P = .04; GrimAge epigenetic clock: β 0.14; P = .01) and aging rates (Dunedin Pace of Aging: β 0.37; P < .001) than those who remained free of BC.

Study details: Findings are from a case-control analysis of the Sister Study cohort including paired blood samples from 417 women collected on an average of 7.7 years apart, of whom 190 women were diagnosed and treated for BC and 227 women remained free of BC.

Disclosures: This study was supported by the Intramural Research Program of the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Kresovich JK et al. Changes in methylation-based aging in women who do and do not develop breast cancer. J Natl Cancer Inst. 2023 (Jul 19). doi: 10.1093/jnci/djad117

Key clinical point: Biological aging was faster in women who were diagnosed and treated for breast cancer (BC) vs women who remained free of BC.

Major finding: Women who were diagnosed and treated for BC had higher epigenetic age acceleration metrics (PhenoAge epigenetic clock: standardized mean difference [β] 0.13; P = .04; GrimAge epigenetic clock: β 0.14; P = .01) and aging rates (Dunedin Pace of Aging: β 0.37; P < .001) than those who remained free of BC.

Study details: Findings are from a case-control analysis of the Sister Study cohort including paired blood samples from 417 women collected on an average of 7.7 years apart, of whom 190 women were diagnosed and treated for BC and 227 women remained free of BC.

Disclosures: This study was supported by the Intramural Research Program of the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Kresovich JK et al. Changes in methylation-based aging in women who do and do not develop breast cancer. J Natl Cancer Inst. 2023 (Jul 19). doi: 10.1093/jnci/djad117

Key clinical point: Biological aging was faster in women who were diagnosed and treated for breast cancer (BC) vs women who remained free of BC.

Major finding: Women who were diagnosed and treated for BC had higher epigenetic age acceleration metrics (PhenoAge epigenetic clock: standardized mean difference [β] 0.13; P = .04; GrimAge epigenetic clock: β 0.14; P = .01) and aging rates (Dunedin Pace of Aging: β 0.37; P < .001) than those who remained free of BC.

Study details: Findings are from a case-control analysis of the Sister Study cohort including paired blood samples from 417 women collected on an average of 7.7 years apart, of whom 190 women were diagnosed and treated for BC and 227 women remained free of BC.

Disclosures: This study was supported by the Intramural Research Program of the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Kresovich JK et al. Changes in methylation-based aging in women who do and do not develop breast cancer. J Natl Cancer Inst. 2023 (Jul 19). doi: 10.1093/jnci/djad117