Breast Cancer ICYMI

Rates of premature return to play (RTP) among student athletes following a sport-related concussion (SRC) have dropped substantially since 2011, according to a recent chart review. Rates of premature return to learn (RTL) are essentially unchanged, however.

“Delay in recovery is the major reason why it’s important not to RTL or RTP prematurely,” said James Carson, MD, associate professor of family and community medicine, University of Toronto.

“That delay in recovery only sets students further back in terms of the stress they get from being delayed with their schoolwork – they could lose their year in school, lose all their social contacts. So, there are a number of psychosocial issues that come into play if recovery is delayed, and that is what premature RTL and premature RTP will do – they delay the student’s recovery,” he emphasized.

The study was published in Canadian Family Physician.
 

Differences by sex

The study involved 241 students who had 258 distinct cases of SRC. The researchers defined premature RTP and RTL as chart records documenting the relapse, recurrence, or worsening of concussion symptoms that accompanied the patient’s RTP or RTL. Between 2011 and 2016, 26.7% of students had evidence of premature RTP, while 42.6% of them had evidence of premature RTL, the authors noted.

Compared with findings from an earlier survey of data from 2006 to 2011, the incidence of premature RTP dropped by 38.6% (P = .0003). In contrast, symptoms associated with premature RTL dropped by only 4.7% from the previous survey. This change was not statistically significant.

There was also a significant difference between males and females in the proportion of SRC cases with relapse of symptoms. Relapse occurred in 43.4% of female athletes with SRC versus 29.7% of male athletes with SRC (P = .023).

Female athletes also had significantly longer times before being cleared for RTP. The mean time was 74.5 days for females, compared with a mean of 42.3 days for male athletes (P < .001). “The median time to RTP clearance was nearly double [for female athletes] at 49 days versus 25 days [for male athletes],” wrote the authors.

The rate of premature RTL was also higher among secondary school students (48.8%), compared with 28% among elementary students and 42% among postsecondary students.
 

More concussions coming?

Before the first consensus conference, organized by the Concussion in Sport Group in 2001, management of concussion was based on rating and grading scales that had no medical evidence to support them, said Dr. Carson. After the consensus conference, it was recommended that physicians manage each concussion individually and, when it came to RTP, recommendations were based upon symptom resolution.

In contrast, there was nothing in the literature regarding how student athletes who sustain a concussion should RTL. Some schools made generous accommodations, and others none. This situation changed around 2011, when experts started publishing data about how better to accommodate student athletes who have a temporary disability for which schools need to introduce temporary accommodations to help them recover.

“Recommendations for RTP essentially had a 12-year head-start,” Dr. Carson emphasized, “and RTL had a much slower start.” Unfortunately, Dr. Carson foresees more athletes sustaining concussions as pandemic restrictions ease over the next few months. “As athletes RTP after the pandemic, they just will not be in game shape,” he said.

“In other words, athletes may not have the neuromuscular control to avoid these injuries as easily,” he added. Worse, athletes may not realize they are not quite ready to return to the expected level of participation so quickly. “I believe this scenario will lead to more concussions that will be difficult to manage in the context of an already strained health care system,” said Dr. Carson.

A limitation of the study was that it was difficult to assess whether all patients followed medical advice consistently.
 

“Very positive shifts”

Commenting on the findings, Nick Reed, PhD, Canada research chair in pediatric concussion and associate professor of occupational science and occupational therapy, University of Toronto, said that sports medicine physicians are seeing “very positive shifts” in concussion awareness and related behaviors such as providing education, support, and accommodations to students within the school environment. “More and more teachers are seeking education to learn what a concussion is and what to do to best support their students with concussion,” he said. Dr. Reed was not involved in the current study.

Indeed, this increasing awareness led to the development of a concussion education tool for teachers – SCHOOLFirst – although Dr. Reed did acknowledge that not all teachers have either the knowledge or the resources they need to optimally support their students with concussion. In the meantime, to reduce the risk of injury, Dr. Reed stressed that it is important for students to wear equipment appropriate for the game being played and to play by the rules.

“It is key to play sports in a way that is fair and respectful and not [engage] in behaviors with the intent of injuring an opponent,” he stressed. It is also important for athletes themselves to know the signs and symptoms of concussion and, if they think they have a concussion, to immediately stop playing, report how they are feeling to a coach, teacher, or parent, and to seek medical assessment to determine if they have a concussion or not.

“The key here is to focus on what the athlete can do after a concussion rather than what they can’t do,” Dr. Reed said. After even a few days of complete rest, students with a concussion can gradually introduce low levels of physical and cognitive activity that won’t make their symptoms worse. This activity can include going back to school with temporary accommodations in place, such as shorter school days and increased rest breaks. “When returning to school and to sport after a concussion, it is important to follow a stepwise and gradual return to activities so that you aren’t doing too much too fast,” Dr. Reed emphasized.

The study was conducted without external funding. Dr. Carson and Dr. Reed reported no conflicts of interest. 

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

Rates of premature return to play (RTP) among student athletes following a sport-related concussion (SRC) have dropped substantially since 2011, according to a recent chart review. Rates of premature return to learn (RTL) are essentially unchanged, however.

“Delay in recovery is the major reason why it’s important not to RTL or RTP prematurely,” said James Carson, MD, associate professor of family and community medicine, University of Toronto.

“That delay in recovery only sets students further back in terms of the stress they get from being delayed with their schoolwork – they could lose their year in school, lose all their social contacts. So, there are a number of psychosocial issues that come into play if recovery is delayed, and that is what premature RTL and premature RTP will do – they delay the student’s recovery,” he emphasized.

The study was published in Canadian Family Physician.
 

Differences by sex

The study involved 241 students who had 258 distinct cases of SRC. The researchers defined premature RTP and RTL as chart records documenting the relapse, recurrence, or worsening of concussion symptoms that accompanied the patient’s RTP or RTL. Between 2011 and 2016, 26.7% of students had evidence of premature RTP, while 42.6% of them had evidence of premature RTL, the authors noted.

Compared with findings from an earlier survey of data from 2006 to 2011, the incidence of premature RTP dropped by 38.6% (P = .0003). In contrast, symptoms associated with premature RTL dropped by only 4.7% from the previous survey. This change was not statistically significant.

There was also a significant difference between males and females in the proportion of SRC cases with relapse of symptoms. Relapse occurred in 43.4% of female athletes with SRC versus 29.7% of male athletes with SRC (P = .023).

Female athletes also had significantly longer times before being cleared for RTP. The mean time was 74.5 days for females, compared with a mean of 42.3 days for male athletes (P < .001). “The median time to RTP clearance was nearly double [for female athletes] at 49 days versus 25 days [for male athletes],” wrote the authors.

The rate of premature RTL was also higher among secondary school students (48.8%), compared with 28% among elementary students and 42% among postsecondary students.
 

More concussions coming?

Before the first consensus conference, organized by the Concussion in Sport Group in 2001, management of concussion was based on rating and grading scales that had no medical evidence to support them, said Dr. Carson. After the consensus conference, it was recommended that physicians manage each concussion individually and, when it came to RTP, recommendations were based upon symptom resolution.

In contrast, there was nothing in the literature regarding how student athletes who sustain a concussion should RTL. Some schools made generous accommodations, and others none. This situation changed around 2011, when experts started publishing data about how better to accommodate student athletes who have a temporary disability for which schools need to introduce temporary accommodations to help them recover.

“Recommendations for RTP essentially had a 12-year head-start,” Dr. Carson emphasized, “and RTL had a much slower start.” Unfortunately, Dr. Carson foresees more athletes sustaining concussions as pandemic restrictions ease over the next few months. “As athletes RTP after the pandemic, they just will not be in game shape,” he said.

“In other words, athletes may not have the neuromuscular control to avoid these injuries as easily,” he added. Worse, athletes may not realize they are not quite ready to return to the expected level of participation so quickly. “I believe this scenario will lead to more concussions that will be difficult to manage in the context of an already strained health care system,” said Dr. Carson.

A limitation of the study was that it was difficult to assess whether all patients followed medical advice consistently.
 

“Very positive shifts”

Commenting on the findings, Nick Reed, PhD, Canada research chair in pediatric concussion and associate professor of occupational science and occupational therapy, University of Toronto, said that sports medicine physicians are seeing “very positive shifts” in concussion awareness and related behaviors such as providing education, support, and accommodations to students within the school environment. “More and more teachers are seeking education to learn what a concussion is and what to do to best support their students with concussion,” he said. Dr. Reed was not involved in the current study.

Indeed, this increasing awareness led to the development of a concussion education tool for teachers – SCHOOLFirst – although Dr. Reed did acknowledge that not all teachers have either the knowledge or the resources they need to optimally support their students with concussion. In the meantime, to reduce the risk of injury, Dr. Reed stressed that it is important for students to wear equipment appropriate for the game being played and to play by the rules.

“It is key to play sports in a way that is fair and respectful and not [engage] in behaviors with the intent of injuring an opponent,” he stressed. It is also important for athletes themselves to know the signs and symptoms of concussion and, if they think they have a concussion, to immediately stop playing, report how they are feeling to a coach, teacher, or parent, and to seek medical assessment to determine if they have a concussion or not.

“The key here is to focus on what the athlete can do after a concussion rather than what they can’t do,” Dr. Reed said. After even a few days of complete rest, students with a concussion can gradually introduce low levels of physical and cognitive activity that won’t make their symptoms worse. This activity can include going back to school with temporary accommodations in place, such as shorter school days and increased rest breaks. “When returning to school and to sport after a concussion, it is important to follow a stepwise and gradual return to activities so that you aren’t doing too much too fast,” Dr. Reed emphasized.

The study was conducted without external funding. Dr. Carson and Dr. Reed reported no conflicts of interest. 

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

Rates of premature return to play (RTP) among student athletes following a sport-related concussion (SRC) have dropped substantially since 2011, according to a recent chart review. Rates of premature return to learn (RTL) are essentially unchanged, however.

“Delay in recovery is the major reason why it’s important not to RTL or RTP prematurely,” said James Carson, MD, associate professor of family and community medicine, University of Toronto.

“That delay in recovery only sets students further back in terms of the stress they get from being delayed with their schoolwork – they could lose their year in school, lose all their social contacts. So, there are a number of psychosocial issues that come into play if recovery is delayed, and that is what premature RTL and premature RTP will do – they delay the student’s recovery,” he emphasized.

The study was published in Canadian Family Physician.
 

Differences by sex

The study involved 241 students who had 258 distinct cases of SRC. The researchers defined premature RTP and RTL as chart records documenting the relapse, recurrence, or worsening of concussion symptoms that accompanied the patient’s RTP or RTL. Between 2011 and 2016, 26.7% of students had evidence of premature RTP, while 42.6% of them had evidence of premature RTL, the authors noted.

Compared with findings from an earlier survey of data from 2006 to 2011, the incidence of premature RTP dropped by 38.6% (P = .0003). In contrast, symptoms associated with premature RTL dropped by only 4.7% from the previous survey. This change was not statistically significant.

There was also a significant difference between males and females in the proportion of SRC cases with relapse of symptoms. Relapse occurred in 43.4% of female athletes with SRC versus 29.7% of male athletes with SRC (P = .023).

Female athletes also had significantly longer times before being cleared for RTP. The mean time was 74.5 days for females, compared with a mean of 42.3 days for male athletes (P < .001). “The median time to RTP clearance was nearly double [for female athletes] at 49 days versus 25 days [for male athletes],” wrote the authors.

The rate of premature RTL was also higher among secondary school students (48.8%), compared with 28% among elementary students and 42% among postsecondary students.
 

More concussions coming?

Before the first consensus conference, organized by the Concussion in Sport Group in 2001, management of concussion was based on rating and grading scales that had no medical evidence to support them, said Dr. Carson. After the consensus conference, it was recommended that physicians manage each concussion individually and, when it came to RTP, recommendations were based upon symptom resolution.

In contrast, there was nothing in the literature regarding how student athletes who sustain a concussion should RTL. Some schools made generous accommodations, and others none. This situation changed around 2011, when experts started publishing data about how better to accommodate student athletes who have a temporary disability for which schools need to introduce temporary accommodations to help them recover.

“Recommendations for RTP essentially had a 12-year head-start,” Dr. Carson emphasized, “and RTL had a much slower start.” Unfortunately, Dr. Carson foresees more athletes sustaining concussions as pandemic restrictions ease over the next few months. “As athletes RTP after the pandemic, they just will not be in game shape,” he said.

“In other words, athletes may not have the neuromuscular control to avoid these injuries as easily,” he added. Worse, athletes may not realize they are not quite ready to return to the expected level of participation so quickly. “I believe this scenario will lead to more concussions that will be difficult to manage in the context of an already strained health care system,” said Dr. Carson.

A limitation of the study was that it was difficult to assess whether all patients followed medical advice consistently.
 

“Very positive shifts”

Commenting on the findings, Nick Reed, PhD, Canada research chair in pediatric concussion and associate professor of occupational science and occupational therapy, University of Toronto, said that sports medicine physicians are seeing “very positive shifts” in concussion awareness and related behaviors such as providing education, support, and accommodations to students within the school environment. “More and more teachers are seeking education to learn what a concussion is and what to do to best support their students with concussion,” he said. Dr. Reed was not involved in the current study.

Indeed, this increasing awareness led to the development of a concussion education tool for teachers – SCHOOLFirst – although Dr. Reed did acknowledge that not all teachers have either the knowledge or the resources they need to optimally support their students with concussion. In the meantime, to reduce the risk of injury, Dr. Reed stressed that it is important for students to wear equipment appropriate for the game being played and to play by the rules.

“It is key to play sports in a way that is fair and respectful and not [engage] in behaviors with the intent of injuring an opponent,” he stressed. It is also important for athletes themselves to know the signs and symptoms of concussion and, if they think they have a concussion, to immediately stop playing, report how they are feeling to a coach, teacher, or parent, and to seek medical assessment to determine if they have a concussion or not.

“The key here is to focus on what the athlete can do after a concussion rather than what they can’t do,” Dr. Reed said. After even a few days of complete rest, students with a concussion can gradually introduce low levels of physical and cognitive activity that won’t make their symptoms worse. This activity can include going back to school with temporary accommodations in place, such as shorter school days and increased rest breaks. “When returning to school and to sport after a concussion, it is important to follow a stepwise and gradual return to activities so that you aren’t doing too much too fast,” Dr. Reed emphasized.

The study was conducted without external funding. Dr. Carson and Dr. Reed reported no conflicts of interest. 

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

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

Impaired vision in older adults is an underrecognized and modifiable dementia risk factor, new research suggests.

Investigators analyzed estimated population attributable fractions (PAFs) associated with dementia in more than 16,000 older adults. A PAF represents the number of dementia cases that could be prevented if a given risk factor were eliminated.

Results showed the PAF of vision impairment was 1.8%, suggesting that healthy vision had the potential to prevent more than 100,000 cases of dementia in the United States.

“Vision impairment and blindness disproportionately impact older adults, yet vision impairment is often preventable or even correctable,” study investigator Joshua Ehrlich MD, assistant professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, said in an interview.

Poor vision affects not only how individuals see the world, but also their systemic health and well-being, Dr. Ehrlich said.

“Accordingly, ensuring that older adults receive appropriate eye care is vital to promoting health, independence, and optimal aging,” he added.

The findings were published online in JAMA Neurology.
 

A surprising omission

There is an “urgent need to identify modifiable risk factors for dementia that can be targeted with interventions to slow cognitive decline and prevent dementia,” the investigators wrote.

In 2020, the Lancet Commission report on dementia prevention, intervention, and care proposed a life-course model of 12 potentially modifiable dementia risk factors. This included lower educational level, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution.

Together, these factors are associated with about 40% of dementia cases worldwide, the report notes.

Vision impairment was not included in this model, “despite considerable evidence that it is associated with an elevated risk of incident dementia and that it may operate through the same pathways as hearing loss,” the current researchers wrote.

“We have known for some time that vision impairment is a risk factor for dementia [and] we also know that a very large fraction of vision impairment, possibly in excess of 80%, is avoidable or has simply yet to be addressed,” Dr. Ehrlich said.

He and his colleagues found it “surprising that vision impairment had been ignored in key models of modifiable dementia risk factors that are used to shape health policy and resource allocation.” They set out to demonstrate that, “in fact, vision impairment is just as influential as a number of other long accepted modifiable dementia risk factors.”

The investigators assessed data from the Health and Retirement Study (HRS), a panel study that surveys more than 20,000 U.S. adults aged 50 years or older every 2 years.

The investigators applied the same methods used by the Lancet Commission to the HRS dataset and added vision impairment to the Lancet life-course model. Air pollution was excluded in their model “because those data were not readily available in the HRS,” the researchers wrote.

They noted the PAF is “based on the population prevalence and relative risk of dementia for each risk factor” and is “weighted, based on a principal components analysis, to account for communality (clustering of risk factors).”
 

A missed prevention opportunity

The sample included 16,690 participants (54% were women, 51.5% were at least age 65, 80.2% were White, 10.6% were Black, 9.2% were other).

In total, the 12 potentially modifiable risk factors used in the researchers’ model were associated with an estimated 62.4% of dementia cases in the United States, with hypertension as the most prevalent risk factor with the highest weighted PAF.
 

A new focus for prevention

Commenting for this article, Suzann Pershing, MD, associate professor of ophthalmology, Stanford (Calif.) University, called the study “particularly important because, despite growing recognition of its importance in relation to cognition, visual impairment is often an underrecognized risk factor.”

The current research “builds on increasingly robust medical literature linking visual impairment and dementia, applying analogous methods to those used for the life course model recently presented by the Lancet Commission to evaluate potentially modifiable dementia risk factors,” said Dr. Pershing, who was not involved with the study.

The investigators “make a compelling argument for inclusion of visual impairment as one of the potentially modifiable risk factors; practicing clinicians and health care systems may consider screening and targeted therapies to address visual impairment, with a goal of population health and contributing to a reduction in future dementia disease burden,” she added.

In an accompanying editorial), Jennifer Deal, PhD, department of epidemiology and Cochlear Center for Hearing and Public Health, Baltimore, and Julio Rojas, MD, PhD, Memory and Aging Center, department of neurology, Weill Institute for Neurosciences, University of California, San Francisco, call the findings “an important reminder that dementia is a social problem in which potentially treatable risk factors, including visual impairment, are highly prevalent in disadvantaged populations.”

The editorialists noted that 90% of cases of vision impairment are “preventable or have yet to be treated. The two “highly cost-effective interventions” of eyeglasses and/or cataract surgery “remain underused both in the U.S. and globally, especially in disadvantaged communities,” they wrote.

They added that more research is needed to “test the effectiveness of interventions to preserve cognitive health by promoting healthy vision.”

The study was supported by grants from the National Institute on Aging, the National Institutes of Health, and Research to Prevent Blindness. The investigators reported no relevant financial relationships. Dr. Deal reported having received grants from the National Institute on Aging. Dr. Rojas reported serving as site principal investigator on clinical trials for Eli Lilly and Eisai and receiving grants from the National Institute on Aging. Dr. Pershing is a consultant for Acumen, and Verana Health (as DigiSight Technologies).

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

Impaired vision in older adults is an underrecognized and modifiable dementia risk factor, new research suggests.

Investigators analyzed estimated population attributable fractions (PAFs) associated with dementia in more than 16,000 older adults. A PAF represents the number of dementia cases that could be prevented if a given risk factor were eliminated.

Results showed the PAF of vision impairment was 1.8%, suggesting that healthy vision had the potential to prevent more than 100,000 cases of dementia in the United States.

“Vision impairment and blindness disproportionately impact older adults, yet vision impairment is often preventable or even correctable,” study investigator Joshua Ehrlich MD, assistant professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, said in an interview.

Poor vision affects not only how individuals see the world, but also their systemic health and well-being, Dr. Ehrlich said.

“Accordingly, ensuring that older adults receive appropriate eye care is vital to promoting health, independence, and optimal aging,” he added.

The findings were published online in JAMA Neurology.
 

A surprising omission

There is an “urgent need to identify modifiable risk factors for dementia that can be targeted with interventions to slow cognitive decline and prevent dementia,” the investigators wrote.

In 2020, the Lancet Commission report on dementia prevention, intervention, and care proposed a life-course model of 12 potentially modifiable dementia risk factors. This included lower educational level, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution.

Together, these factors are associated with about 40% of dementia cases worldwide, the report notes.

Vision impairment was not included in this model, “despite considerable evidence that it is associated with an elevated risk of incident dementia and that it may operate through the same pathways as hearing loss,” the current researchers wrote.

“We have known for some time that vision impairment is a risk factor for dementia [and] we also know that a very large fraction of vision impairment, possibly in excess of 80%, is avoidable or has simply yet to be addressed,” Dr. Ehrlich said.

He and his colleagues found it “surprising that vision impairment had been ignored in key models of modifiable dementia risk factors that are used to shape health policy and resource allocation.” They set out to demonstrate that, “in fact, vision impairment is just as influential as a number of other long accepted modifiable dementia risk factors.”

The investigators assessed data from the Health and Retirement Study (HRS), a panel study that surveys more than 20,000 U.S. adults aged 50 years or older every 2 years.

The investigators applied the same methods used by the Lancet Commission to the HRS dataset and added vision impairment to the Lancet life-course model. Air pollution was excluded in their model “because those data were not readily available in the HRS,” the researchers wrote.

They noted the PAF is “based on the population prevalence and relative risk of dementia for each risk factor” and is “weighted, based on a principal components analysis, to account for communality (clustering of risk factors).”
 

A missed prevention opportunity

The sample included 16,690 participants (54% were women, 51.5% were at least age 65, 80.2% were White, 10.6% were Black, 9.2% were other).

In total, the 12 potentially modifiable risk factors used in the researchers’ model were associated with an estimated 62.4% of dementia cases in the United States, with hypertension as the most prevalent risk factor with the highest weighted PAF.
 

A new focus for prevention

Commenting for this article, Suzann Pershing, MD, associate professor of ophthalmology, Stanford (Calif.) University, called the study “particularly important because, despite growing recognition of its importance in relation to cognition, visual impairment is often an underrecognized risk factor.”

The current research “builds on increasingly robust medical literature linking visual impairment and dementia, applying analogous methods to those used for the life course model recently presented by the Lancet Commission to evaluate potentially modifiable dementia risk factors,” said Dr. Pershing, who was not involved with the study.

The investigators “make a compelling argument for inclusion of visual impairment as one of the potentially modifiable risk factors; practicing clinicians and health care systems may consider screening and targeted therapies to address visual impairment, with a goal of population health and contributing to a reduction in future dementia disease burden,” she added.

In an accompanying editorial), Jennifer Deal, PhD, department of epidemiology and Cochlear Center for Hearing and Public Health, Baltimore, and Julio Rojas, MD, PhD, Memory and Aging Center, department of neurology, Weill Institute for Neurosciences, University of California, San Francisco, call the findings “an important reminder that dementia is a social problem in which potentially treatable risk factors, including visual impairment, are highly prevalent in disadvantaged populations.”

The editorialists noted that 90% of cases of vision impairment are “preventable or have yet to be treated. The two “highly cost-effective interventions” of eyeglasses and/or cataract surgery “remain underused both in the U.S. and globally, especially in disadvantaged communities,” they wrote.

They added that more research is needed to “test the effectiveness of interventions to preserve cognitive health by promoting healthy vision.”

The study was supported by grants from the National Institute on Aging, the National Institutes of Health, and Research to Prevent Blindness. The investigators reported no relevant financial relationships. Dr. Deal reported having received grants from the National Institute on Aging. Dr. Rojas reported serving as site principal investigator on clinical trials for Eli Lilly and Eisai and receiving grants from the National Institute on Aging. Dr. Pershing is a consultant for Acumen, and Verana Health (as DigiSight Technologies).

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

Impaired vision in older adults is an underrecognized and modifiable dementia risk factor, new research suggests.

Investigators analyzed estimated population attributable fractions (PAFs) associated with dementia in more than 16,000 older adults. A PAF represents the number of dementia cases that could be prevented if a given risk factor were eliminated.

Results showed the PAF of vision impairment was 1.8%, suggesting that healthy vision had the potential to prevent more than 100,000 cases of dementia in the United States.

“Vision impairment and blindness disproportionately impact older adults, yet vision impairment is often preventable or even correctable,” study investigator Joshua Ehrlich MD, assistant professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, said in an interview.

Poor vision affects not only how individuals see the world, but also their systemic health and well-being, Dr. Ehrlich said.

“Accordingly, ensuring that older adults receive appropriate eye care is vital to promoting health, independence, and optimal aging,” he added.

The findings were published online in JAMA Neurology.
 

A surprising omission

There is an “urgent need to identify modifiable risk factors for dementia that can be targeted with interventions to slow cognitive decline and prevent dementia,” the investigators wrote.

In 2020, the Lancet Commission report on dementia prevention, intervention, and care proposed a life-course model of 12 potentially modifiable dementia risk factors. This included lower educational level, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution.

Together, these factors are associated with about 40% of dementia cases worldwide, the report notes.

Vision impairment was not included in this model, “despite considerable evidence that it is associated with an elevated risk of incident dementia and that it may operate through the same pathways as hearing loss,” the current researchers wrote.

“We have known for some time that vision impairment is a risk factor for dementia [and] we also know that a very large fraction of vision impairment, possibly in excess of 80%, is avoidable or has simply yet to be addressed,” Dr. Ehrlich said.

He and his colleagues found it “surprising that vision impairment had been ignored in key models of modifiable dementia risk factors that are used to shape health policy and resource allocation.” They set out to demonstrate that, “in fact, vision impairment is just as influential as a number of other long accepted modifiable dementia risk factors.”

The investigators assessed data from the Health and Retirement Study (HRS), a panel study that surveys more than 20,000 U.S. adults aged 50 years or older every 2 years.

The investigators applied the same methods used by the Lancet Commission to the HRS dataset and added vision impairment to the Lancet life-course model. Air pollution was excluded in their model “because those data were not readily available in the HRS,” the researchers wrote.

They noted the PAF is “based on the population prevalence and relative risk of dementia for each risk factor” and is “weighted, based on a principal components analysis, to account for communality (clustering of risk factors).”
 

A missed prevention opportunity

The sample included 16,690 participants (54% were women, 51.5% were at least age 65, 80.2% were White, 10.6% were Black, 9.2% were other).

In total, the 12 potentially modifiable risk factors used in the researchers’ model were associated with an estimated 62.4% of dementia cases in the United States, with hypertension as the most prevalent risk factor with the highest weighted PAF.
 

A new focus for prevention

Commenting for this article, Suzann Pershing, MD, associate professor of ophthalmology, Stanford (Calif.) University, called the study “particularly important because, despite growing recognition of its importance in relation to cognition, visual impairment is often an underrecognized risk factor.”

The current research “builds on increasingly robust medical literature linking visual impairment and dementia, applying analogous methods to those used for the life course model recently presented by the Lancet Commission to evaluate potentially modifiable dementia risk factors,” said Dr. Pershing, who was not involved with the study.

The investigators “make a compelling argument for inclusion of visual impairment as one of the potentially modifiable risk factors; practicing clinicians and health care systems may consider screening and targeted therapies to address visual impairment, with a goal of population health and contributing to a reduction in future dementia disease burden,” she added.

In an accompanying editorial), Jennifer Deal, PhD, department of epidemiology and Cochlear Center for Hearing and Public Health, Baltimore, and Julio Rojas, MD, PhD, Memory and Aging Center, department of neurology, Weill Institute for Neurosciences, University of California, San Francisco, call the findings “an important reminder that dementia is a social problem in which potentially treatable risk factors, including visual impairment, are highly prevalent in disadvantaged populations.”

The editorialists noted that 90% of cases of vision impairment are “preventable or have yet to be treated. The two “highly cost-effective interventions” of eyeglasses and/or cataract surgery “remain underused both in the U.S. and globally, especially in disadvantaged communities,” they wrote.

They added that more research is needed to “test the effectiveness of interventions to preserve cognitive health by promoting healthy vision.”

The study was supported by grants from the National Institute on Aging, the National Institutes of Health, and Research to Prevent Blindness. The investigators reported no relevant financial relationships. Dr. Deal reported having received grants from the National Institute on Aging. Dr. Rojas reported serving as site principal investigator on clinical trials for Eli Lilly and Eisai and receiving grants from the National Institute on Aging. Dr. Pershing is a consultant for Acumen, and Verana Health (as DigiSight Technologies).

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

Moderate to severe anxiety, depression, and shortness of breath indicate increased risk for nonfatal self-injury (NFSI) among patients newly diagnosed with cancer, according to a Canadian study.

In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.

“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.

Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”

The study was published online in JAMA Oncology.
 

Nine common symptoms

The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).

The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
 

Toward tailored intervention

A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).

“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”

In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.

“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
 

Self-injury vs. suicidality

Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.

“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”

The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.

“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.

The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.

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

Moderate to severe anxiety, depression, and shortness of breath indicate increased risk for nonfatal self-injury (NFSI) among patients newly diagnosed with cancer, according to a Canadian study.

In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.

“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.

Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”

The study was published online in JAMA Oncology.
 

Nine common symptoms

The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).

The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
 

Toward tailored intervention

A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).

“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”

In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.

“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
 

Self-injury vs. suicidality

Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.

“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”

The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.

“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.

The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.

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

Moderate to severe anxiety, depression, and shortness of breath indicate increased risk for nonfatal self-injury (NFSI) among patients newly diagnosed with cancer, according to a Canadian study.

In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.

“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.

Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”

The study was published online in JAMA Oncology.
 

Nine common symptoms

The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).

The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
 

Toward tailored intervention

A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).

“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”

In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.

“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
 

Self-injury vs. suicidality

Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.

“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”

The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.

“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.

The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.

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

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Many patients with early-stage HR+/HER2- breast cancer are at high risk for disease recurrence within just a few years of first-line treatment. In this ReCAP, Michelle Melisko, MD, of the University of San Francisco Medical Center, discusses strategies for reducing recurrence rates in these patients.

Dr Melisko begins by identifying the traditional criteria for selecting treatment, including age, comorbidities, tumor size, and nodal status, along with proper utilization of genomic assays. She notes that the RxPONDER and TAILORx trials have demonstrated benefits of chemotherapy plus endocrine therapy in premenopausal patients on the basis of Oncotype DX recurrence scores between 0 and 25.

Next, Dr Melisko discusses how the 2021 FDA approval of abemaciclib plus endocrine therapy in the adjuvant setting mandates that patients have a Ki-67 score of 20%. This is a more restrictive patient population than those who saw benefit in the monarchE clinical trial and presents a challenge for physicians selecting therapy for their patients.

Dr Melisko concludes by sharing 3-year data from the OlympiA trial supporting the use of olaparib in patients with BRCA1 and BRCA2 mutations, as well as findings from the SOFT/TEXT trials that demonstrated the benefit of ovarian suppression in younger patients.

--

Michelle E. Melisko, MD, Associate Clinical Professor, Department of Medicine, Division of Hematology-Oncology, University of San Francisco Medical Center; UCSF Bakar Precision Cancer Medicine, San Francisco, California

Michelle E. Melisko, MD, has disclosed no relevant financial relationships

Many patients with early-stage HR+/HER2- breast cancer are at high risk for disease recurrence within just a few years of first-line treatment. In this ReCAP, Michelle Melisko, MD, of the University of San Francisco Medical Center, discusses strategies for reducing recurrence rates in these patients.

Dr Melisko begins by identifying the traditional criteria for selecting treatment, including age, comorbidities, tumor size, and nodal status, along with proper utilization of genomic assays. She notes that the RxPONDER and TAILORx trials have demonstrated benefits of chemotherapy plus endocrine therapy in premenopausal patients on the basis of Oncotype DX recurrence scores between 0 and 25.

Next, Dr Melisko discusses how the 2021 FDA approval of abemaciclib plus endocrine therapy in the adjuvant setting mandates that patients have a Ki-67 score of 20%. This is a more restrictive patient population than those who saw benefit in the monarchE clinical trial and presents a challenge for physicians selecting therapy for their patients.

Dr Melisko concludes by sharing 3-year data from the OlympiA trial supporting the use of olaparib in patients with BRCA1 and BRCA2 mutations, as well as findings from the SOFT/TEXT trials that demonstrated the benefit of ovarian suppression in younger patients.

--

Michelle E. Melisko, MD, Associate Clinical Professor, Department of Medicine, Division of Hematology-Oncology, University of San Francisco Medical Center; UCSF Bakar Precision Cancer Medicine, San Francisco, California

Michelle E. Melisko, MD, has disclosed no relevant financial relationships

Many patients with early-stage HR+/HER2- breast cancer are at high risk for disease recurrence within just a few years of first-line treatment. In this ReCAP, Michelle Melisko, MD, of the University of San Francisco Medical Center, discusses strategies for reducing recurrence rates in these patients.

Dr Melisko begins by identifying the traditional criteria for selecting treatment, including age, comorbidities, tumor size, and nodal status, along with proper utilization of genomic assays. She notes that the RxPONDER and TAILORx trials have demonstrated benefits of chemotherapy plus endocrine therapy in premenopausal patients on the basis of Oncotype DX recurrence scores between 0 and 25.

Next, Dr Melisko discusses how the 2021 FDA approval of abemaciclib plus endocrine therapy in the adjuvant setting mandates that patients have a Ki-67 score of 20%. This is a more restrictive patient population than those who saw benefit in the monarchE clinical trial and presents a challenge for physicians selecting therapy for their patients.

Dr Melisko concludes by sharing 3-year data from the OlympiA trial supporting the use of olaparib in patients with BRCA1 and BRCA2 mutations, as well as findings from the SOFT/TEXT trials that demonstrated the benefit of ovarian suppression in younger patients.

--

Michelle E. Melisko, MD, Associate Clinical Professor, Department of Medicine, Division of Hematology-Oncology, University of San Francisco Medical Center; UCSF Bakar Precision Cancer Medicine, San Francisco, California

Michelle E. Melisko, MD, has disclosed no relevant financial relationships

BOSTON – According to the best available data, solid organ transplant recipients (SOTRs) at highest risk for developing skin cancer are thoracic organ recipients, those aged 50 or older at the time of the transplant, and males.

White patients who meet these criteria should be screening within 2 years after transplant, while Black patients should be screened within 5 years after transplant, Ally-Khan Somani, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Dr. Somani, director of dermatologic surgery and the division of cutaneous oncology at Indiana University, Indianapolis, based his remarks on consensus screening guidelines assembled from three rounds of Delphi method surveys with 47 dermatologists and 37 transplant physicians, with the goal of establishing skin cancer screening recommendations for SOTRs. Among the dermatologists surveyed, 45% were Mohs surgeons and 55% were general dermatologists.

The panel recommended that the transplant team should perform risk assessment for SOTRs to risk stratify patients for skin cancer screening (high risk vs. low risk). They also proposed that dermatologists perform skin cancer screening by full-body skin examinations, and that SOTRs with a history of skin cancer should continue with routine skin cancer surveillance as recommended by their dermatologists.

Those at low risk for skin cancer include abdominal organ recipients, SOTR age of younger than 50 at time of transplant, and female gender. The guidelines recommend that White, Asian, and Hispanic patients who meet those criteria should be screened within 5 years after transplant, while no consensus was reached for Black patients who meet those criteria.

Based on posttransplant skin cancer incidence rates, risk is increased among males, Whites, thoracic organ recipients, and being age 50 or older, Dr. Somani said. “At our institution, we make sure there’s a good connection between our transplant teams and dermatologists. We recommend rapid referral for suspicious lesions and we educate patients and screen them within 1 year of transplant, or sooner for high-risk patients. Surveillance is increased to every 3 or 4 months for patients with a history of multiple or high-risk cancers or sooner, followed by routine surveillance as recommended by the patient’s dermatologist.”

To risk stratify patients on the development of their first skin cancer post transplantation, researchers developed the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), a prediction tool with a freely available app. Data for the tool were drawn from the Transplant Skin Cancer Network study, a 5-year analysis of 6,340 adult recipients of a first solid organ transplant at 26 transplant centers in the United States. It generates a risk score for SOTRs (low, medium, high, or very high), which informs transplant care providers of a patient’s risk of skin cancer.

Dr. Somani disclosed that he has received grants and funding from Castle Biosciences. He is an adviser to Cook Biotech and a consultant to Sanara MedTech.

BOSTON – According to the best available data, solid organ transplant recipients (SOTRs) at highest risk for developing skin cancer are thoracic organ recipients, those aged 50 or older at the time of the transplant, and males.

White patients who meet these criteria should be screening within 2 years after transplant, while Black patients should be screened within 5 years after transplant, Ally-Khan Somani, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Dr. Somani, director of dermatologic surgery and the division of cutaneous oncology at Indiana University, Indianapolis, based his remarks on consensus screening guidelines assembled from three rounds of Delphi method surveys with 47 dermatologists and 37 transplant physicians, with the goal of establishing skin cancer screening recommendations for SOTRs. Among the dermatologists surveyed, 45% were Mohs surgeons and 55% were general dermatologists.

The panel recommended that the transplant team should perform risk assessment for SOTRs to risk stratify patients for skin cancer screening (high risk vs. low risk). They also proposed that dermatologists perform skin cancer screening by full-body skin examinations, and that SOTRs with a history of skin cancer should continue with routine skin cancer surveillance as recommended by their dermatologists.

Those at low risk for skin cancer include abdominal organ recipients, SOTR age of younger than 50 at time of transplant, and female gender. The guidelines recommend that White, Asian, and Hispanic patients who meet those criteria should be screened within 5 years after transplant, while no consensus was reached for Black patients who meet those criteria.

Based on posttransplant skin cancer incidence rates, risk is increased among males, Whites, thoracic organ recipients, and being age 50 or older, Dr. Somani said. “At our institution, we make sure there’s a good connection between our transplant teams and dermatologists. We recommend rapid referral for suspicious lesions and we educate patients and screen them within 1 year of transplant, or sooner for high-risk patients. Surveillance is increased to every 3 or 4 months for patients with a history of multiple or high-risk cancers or sooner, followed by routine surveillance as recommended by the patient’s dermatologist.”

To risk stratify patients on the development of their first skin cancer post transplantation, researchers developed the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), a prediction tool with a freely available app. Data for the tool were drawn from the Transplant Skin Cancer Network study, a 5-year analysis of 6,340 adult recipients of a first solid organ transplant at 26 transplant centers in the United States. It generates a risk score for SOTRs (low, medium, high, or very high), which informs transplant care providers of a patient’s risk of skin cancer.

Dr. Somani disclosed that he has received grants and funding from Castle Biosciences. He is an adviser to Cook Biotech and a consultant to Sanara MedTech.

BOSTON – According to the best available data, solid organ transplant recipients (SOTRs) at highest risk for developing skin cancer are thoracic organ recipients, those aged 50 or older at the time of the transplant, and males.

White patients who meet these criteria should be screening within 2 years after transplant, while Black patients should be screened within 5 years after transplant, Ally-Khan Somani, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Dr. Somani, director of dermatologic surgery and the division of cutaneous oncology at Indiana University, Indianapolis, based his remarks on consensus screening guidelines assembled from three rounds of Delphi method surveys with 47 dermatologists and 37 transplant physicians, with the goal of establishing skin cancer screening recommendations for SOTRs. Among the dermatologists surveyed, 45% were Mohs surgeons and 55% were general dermatologists.

The panel recommended that the transplant team should perform risk assessment for SOTRs to risk stratify patients for skin cancer screening (high risk vs. low risk). They also proposed that dermatologists perform skin cancer screening by full-body skin examinations, and that SOTRs with a history of skin cancer should continue with routine skin cancer surveillance as recommended by their dermatologists.

Those at low risk for skin cancer include abdominal organ recipients, SOTR age of younger than 50 at time of transplant, and female gender. The guidelines recommend that White, Asian, and Hispanic patients who meet those criteria should be screened within 5 years after transplant, while no consensus was reached for Black patients who meet those criteria.

Based on posttransplant skin cancer incidence rates, risk is increased among males, Whites, thoracic organ recipients, and being age 50 or older, Dr. Somani said. “At our institution, we make sure there’s a good connection between our transplant teams and dermatologists. We recommend rapid referral for suspicious lesions and we educate patients and screen them within 1 year of transplant, or sooner for high-risk patients. Surveillance is increased to every 3 or 4 months for patients with a history of multiple or high-risk cancers or sooner, followed by routine surveillance as recommended by the patient’s dermatologist.”

To risk stratify patients on the development of their first skin cancer post transplantation, researchers developed the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), a prediction tool with a freely available app. Data for the tool were drawn from the Transplant Skin Cancer Network study, a 5-year analysis of 6,340 adult recipients of a first solid organ transplant at 26 transplant centers in the United States. It generates a risk score for SOTRs (low, medium, high, or very high), which informs transplant care providers of a patient’s risk of skin cancer.

Dr. Somani disclosed that he has received grants and funding from Castle Biosciences. He is an adviser to Cook Biotech and a consultant to Sanara MedTech.

Key clinical point: Pyrotinib-based therapy could prolong survival in patients with lapatinib-resistant, human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, including those with brain metastases and those who benefitted from prior lapatinib.

Major finding: The overall survival was not reached, and the median progression-free survival (PFS) was 8 months (95% CI 5.1-10.9) in the overall cohort and 7.1 (95% CI 5.6-8.6) months in patients with brain metastases. Patients who benefitted from lapatinib therapy ≥6 vs. <6 months prior had a longer PFS after pyrotinib treatment (P = .034). Diarrhea was the most common grade 3-4 adverse event (14.5%).

Study details: This real-world study included 76 patients with HER2+ metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression.

Disclosures: This work was financially supported by the National Key Research and Development Program of China, High-level Innovation Team of Nanjing Medical University, and other sources. The authors declared no conflicts of interest.

Source: Hua Y et al. Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study. Ther Adv Med Oncol. 2022;14 :1-9 (Mar 24). Doi: 10.1177/17588359221085232

Key clinical point: Pyrotinib-based therapy could prolong survival in patients with lapatinib-resistant, human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, including those with brain metastases and those who benefitted from prior lapatinib.

Major finding: The overall survival was not reached, and the median progression-free survival (PFS) was 8 months (95% CI 5.1-10.9) in the overall cohort and 7.1 (95% CI 5.6-8.6) months in patients with brain metastases. Patients who benefitted from lapatinib therapy ≥6 vs. <6 months prior had a longer PFS after pyrotinib treatment (P = .034). Diarrhea was the most common grade 3-4 adverse event (14.5%).

Study details: This real-world study included 76 patients with HER2+ metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression.

Disclosures: This work was financially supported by the National Key Research and Development Program of China, High-level Innovation Team of Nanjing Medical University, and other sources. The authors declared no conflicts of interest.

Source: Hua Y et al. Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study. Ther Adv Med Oncol. 2022;14 :1-9 (Mar 24). Doi: 10.1177/17588359221085232

Key clinical point: Pyrotinib-based therapy could prolong survival in patients with lapatinib-resistant, human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, including those with brain metastases and those who benefitted from prior lapatinib.

Major finding: The overall survival was not reached, and the median progression-free survival (PFS) was 8 months (95% CI 5.1-10.9) in the overall cohort and 7.1 (95% CI 5.6-8.6) months in patients with brain metastases. Patients who benefitted from lapatinib therapy ≥6 vs. <6 months prior had a longer PFS after pyrotinib treatment (P = .034). Diarrhea was the most common grade 3-4 adverse event (14.5%).

Study details: This real-world study included 76 patients with HER2+ metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression.

Disclosures: This work was financially supported by the National Key Research and Development Program of China, High-level Innovation Team of Nanjing Medical University, and other sources. The authors declared no conflicts of interest.

Source: Hua Y et al. Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study. Ther Adv Med Oncol. 2022;14 :1-9 (Mar 24). Doi: 10.1177/17588359221085232

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053