Breast Cancer ICYMI

Food emulsifiers are among the most widespread food additives. A large cohort study highlighted an association between the consumption of certain emulsifiers and an increased risk for certain cancers, particularly breast and prostate cancer.

Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.

Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.

Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.

The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.

In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).

Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.

In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.

The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.

It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Food emulsifiers are among the most widespread food additives. A large cohort study highlighted an association between the consumption of certain emulsifiers and an increased risk for certain cancers, particularly breast and prostate cancer.

Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.

Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.

Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.

The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.

In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).

Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.

In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.

The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.

It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Food emulsifiers are among the most widespread food additives. A large cohort study highlighted an association between the consumption of certain emulsifiers and an increased risk for certain cancers, particularly breast and prostate cancer.

Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.

Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.

Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.

The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.

In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).

Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.

In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.

The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.

It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A combination of adjuvant abemaciclib and endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer, in updated results of a trial.

This was based on data collected over a median follow-up of 54 months. Previously reported data from this phase III study, known as monarchE, showed the same outcomes but over a 2-year treatment period, the researchers said.

Risk of cancer recurrence may be as much as 30% at 5 years in these high-risk patients, who will likely need more intense treatment, wrote Priya Rastogi, MD, of the University of Pittsburgh Medical Center, and colleagues.

In the new study published in the Journal of Clinical Oncology (2023 Jan 9. doi: 10.1200/JCO.23.019), the researchers reported 5-year efficacy results from an interim analysis of overall survival in the monarchE trial.

The intent-to-treat population included 2808 individuals randomized to abemaciclib plus ET and 2814 to ET alone; the median age was 51 years, and approximately 70% of the participants were White.

The addition of abemaciclib significantly reduced the risk of IDFS and DRFS over a median follow-up period of 54 months with hazard ratios of 0.680 and 0.675, respectively. Adjuvant abemaciclib also significantly improved DRFS over ET alone (HR 0.675).

The findings were limited by the lack of statistical significance for overall survival with abemaciclib. However, the increased benefits for IDFS and DRFS with abemaciclib plus ET vs. ET alone were consistent across all subgroups, and the benefit of abemaciclib was consistent regardless of the number of nodes involved, the researchers wrote.

“Prior reports from this trial with shorter follow-up demonstrated benefit of abemaciclib. However, with longer follow-up of a median 54 months, we see that the benefit of the drug is not only sustained (32% reduction in the risk of a disease event), but that there is further separation of the curves with an absolute difference in IDFS and DRFS rates of 7.6% and 6.7, comparing the ET alone vs. ET plus abemaciclib arms,” study coauthor Matthew P. Goetz, MD, said in an interview.

Although statistical significance was not reached for overall survival, fewer deaths occurred in the abemaciclib-plus-ET group compared with the ET-only group, said Dr. Goetz, of the Mayo Clinic, Rochester, Minnesota. However, patients with the worst prognosis (Ki-67–high subgroup) tended to have higher overall survival.

A total of 208 deaths occurred in the combination group vs. 234 in the ET-only group, and no new safety signals were observed. The occurrence of serious adverse events of any cause was similar in the abemaciclib group and the ET-only group (6.5% vs. 7.3%).

“These data are a pleasant surprise, as there were concerns that the benefit of the drug seen with shorter follow-up would wane over time,” Dr. Goetz said. “However, the opposite has occurred; with increasing length of follow-up, the curves continue to separate.”

Based on the new results, “we have high confidence that for patients with ER+/HER2- breast cancer at high risk of recurrence, the addition of 2 years of adjuvant abemaciclib to ET results in clinically significant improvements in IDFS,” he said.

Looking ahead, “we need additional follow-up to determine whether the benefit we now see in terms of IDFS will eventually translate into improvements in overall survival,” Dr. Goetz said. “We need to identify biomarkers that can identify patients at risk for early recurrence despite administration of adjuvant abemaciclib and further, biomarkers that will allow us to select patients that can be safely treated with ET alone.”

 

Findings Confirm Value of Combined Treatment

“It was reassuring to see the continued benefit at 5 years with adjuvant abemaciclib in combination with endocrine therapy compared to endocrine therapy alone in this high-risk HR+, HER2– EBC [early breast cancer] population,” Manali Ajay Bhave, MD, a medical oncologist at Emory University, Atlanta, said in an interview.

“While the interim overall survival analysis was not significant, further follow-up is necessary to truly discern a survival benefit particularly in this patient population where a survival advantage may not be seen for several years,” she added.

The current study supports the continued use of adjuvant abemaciclib in high-risk HR+, HER2– EBC patients, Dr. Bhave said. “Investigation of novel endocrine agents in the adjuvant setting for patients with high risk, HR+ HER2– EBC is needed to further improve outcomes.”
 

Urgent Need to Improve Adjuvant Therapy

“The monarchE study is a timely study aimed at improving adjuvant treatments in ER+ breast cancer to reduce risk of late recurrences,” Malinda T. West, MD, of the University of Wisconsin, said in an interview. “Late recurrences occurring decades later is a risk associated with ER+ breast cancer, and the risk of breast cancer recurrence is highest in those with larger tumors and nodal involvement.

“Abemaciclib is one of the three FDA-approved cyclin-dependent kinase 4/6 inhibitors in metastatic ER+ breast cancer based on demonstrated efficacy and safety in the metastatic setting compared to endocrine therapy alone, which was the rationale for expanded use of abemaciclib into the adjuvant setting for those at high risk for recurrence and basis of the monarchE trial,” said Dr. West.

An important criterion for inclusion was the randomization to abemaciclib required within 16 months of definitive breast cancer surgery, which reflected a window of time in which to start adjuvant abemaciclib, Dr. West said. “Exclusion criteria were those with a history of thromboembolic events, as abemaciclib carries a warning for venous thromboembolism,” she added.

In the monarchE follow-up, Dr. West said she was encouraged by the persistent and widening benefit with 2 years of added abemaciclib to endocrine therapy in reducing IDFS and DRFS compared to endocrine therapy alone.

Dr. West advised clinicians to consider initiating the therapy for up to 16 months after definitive breast surgery, because doing so may allow for recovery from surgery, chemotherapy, and radiation.

The findings tell physicians to “use caution with adding abemaciclib in those with a history of thromboembolic events or VTE risk factors as abemaciclib has a known VTE warning and this population was excluded in the monarchE trial,” she noted.

“Continued long-term follow up of those in this study will be important to determine survival benefits and how the predictive biomarker Ki-67 may impact survival outcomes,” she said.

The study was supported by Eli Lilly. Lead author Dr. Rastogi disclosed travel, accommodations, and expenses from Genentech/Roche, Lilly, and AstraZeneca. Several coauthors disclosed stock or ownership interests and/or other relationships with Lilly and other pharmaceutical companies. Dr. Goetz receives research funding from the National Institutes of Health. Dr. Bhave and Dr. West had no financial conflicts to disclose.

A combination of adjuvant abemaciclib and endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer, in updated results of a trial.

This was based on data collected over a median follow-up of 54 months. Previously reported data from this phase III study, known as monarchE, showed the same outcomes but over a 2-year treatment period, the researchers said.

Risk of cancer recurrence may be as much as 30% at 5 years in these high-risk patients, who will likely need more intense treatment, wrote Priya Rastogi, MD, of the University of Pittsburgh Medical Center, and colleagues.

In the new study published in the Journal of Clinical Oncology (2023 Jan 9. doi: 10.1200/JCO.23.019), the researchers reported 5-year efficacy results from an interim analysis of overall survival in the monarchE trial.

The intent-to-treat population included 2808 individuals randomized to abemaciclib plus ET and 2814 to ET alone; the median age was 51 years, and approximately 70% of the participants were White.

The addition of abemaciclib significantly reduced the risk of IDFS and DRFS over a median follow-up period of 54 months with hazard ratios of 0.680 and 0.675, respectively. Adjuvant abemaciclib also significantly improved DRFS over ET alone (HR 0.675).

The findings were limited by the lack of statistical significance for overall survival with abemaciclib. However, the increased benefits for IDFS and DRFS with abemaciclib plus ET vs. ET alone were consistent across all subgroups, and the benefit of abemaciclib was consistent regardless of the number of nodes involved, the researchers wrote.

“Prior reports from this trial with shorter follow-up demonstrated benefit of abemaciclib. However, with longer follow-up of a median 54 months, we see that the benefit of the drug is not only sustained (32% reduction in the risk of a disease event), but that there is further separation of the curves with an absolute difference in IDFS and DRFS rates of 7.6% and 6.7, comparing the ET alone vs. ET plus abemaciclib arms,” study coauthor Matthew P. Goetz, MD, said in an interview.

Although statistical significance was not reached for overall survival, fewer deaths occurred in the abemaciclib-plus-ET group compared with the ET-only group, said Dr. Goetz, of the Mayo Clinic, Rochester, Minnesota. However, patients with the worst prognosis (Ki-67–high subgroup) tended to have higher overall survival.

A total of 208 deaths occurred in the combination group vs. 234 in the ET-only group, and no new safety signals were observed. The occurrence of serious adverse events of any cause was similar in the abemaciclib group and the ET-only group (6.5% vs. 7.3%).

“These data are a pleasant surprise, as there were concerns that the benefit of the drug seen with shorter follow-up would wane over time,” Dr. Goetz said. “However, the opposite has occurred; with increasing length of follow-up, the curves continue to separate.”

Based on the new results, “we have high confidence that for patients with ER+/HER2- breast cancer at high risk of recurrence, the addition of 2 years of adjuvant abemaciclib to ET results in clinically significant improvements in IDFS,” he said.

Looking ahead, “we need additional follow-up to determine whether the benefit we now see in terms of IDFS will eventually translate into improvements in overall survival,” Dr. Goetz said. “We need to identify biomarkers that can identify patients at risk for early recurrence despite administration of adjuvant abemaciclib and further, biomarkers that will allow us to select patients that can be safely treated with ET alone.”

 

Findings Confirm Value of Combined Treatment

“It was reassuring to see the continued benefit at 5 years with adjuvant abemaciclib in combination with endocrine therapy compared to endocrine therapy alone in this high-risk HR+, HER2– EBC [early breast cancer] population,” Manali Ajay Bhave, MD, a medical oncologist at Emory University, Atlanta, said in an interview.

“While the interim overall survival analysis was not significant, further follow-up is necessary to truly discern a survival benefit particularly in this patient population where a survival advantage may not be seen for several years,” she added.

The current study supports the continued use of adjuvant abemaciclib in high-risk HR+, HER2– EBC patients, Dr. Bhave said. “Investigation of novel endocrine agents in the adjuvant setting for patients with high risk, HR+ HER2– EBC is needed to further improve outcomes.”
 

Urgent Need to Improve Adjuvant Therapy

“The monarchE study is a timely study aimed at improving adjuvant treatments in ER+ breast cancer to reduce risk of late recurrences,” Malinda T. West, MD, of the University of Wisconsin, said in an interview. “Late recurrences occurring decades later is a risk associated with ER+ breast cancer, and the risk of breast cancer recurrence is highest in those with larger tumors and nodal involvement.

“Abemaciclib is one of the three FDA-approved cyclin-dependent kinase 4/6 inhibitors in metastatic ER+ breast cancer based on demonstrated efficacy and safety in the metastatic setting compared to endocrine therapy alone, which was the rationale for expanded use of abemaciclib into the adjuvant setting for those at high risk for recurrence and basis of the monarchE trial,” said Dr. West.

An important criterion for inclusion was the randomization to abemaciclib required within 16 months of definitive breast cancer surgery, which reflected a window of time in which to start adjuvant abemaciclib, Dr. West said. “Exclusion criteria were those with a history of thromboembolic events, as abemaciclib carries a warning for venous thromboembolism,” she added.

In the monarchE follow-up, Dr. West said she was encouraged by the persistent and widening benefit with 2 years of added abemaciclib to endocrine therapy in reducing IDFS and DRFS compared to endocrine therapy alone.

Dr. West advised clinicians to consider initiating the therapy for up to 16 months after definitive breast surgery, because doing so may allow for recovery from surgery, chemotherapy, and radiation.

The findings tell physicians to “use caution with adding abemaciclib in those with a history of thromboembolic events or VTE risk factors as abemaciclib has a known VTE warning and this population was excluded in the monarchE trial,” she noted.

“Continued long-term follow up of those in this study will be important to determine survival benefits and how the predictive biomarker Ki-67 may impact survival outcomes,” she said.

The study was supported by Eli Lilly. Lead author Dr. Rastogi disclosed travel, accommodations, and expenses from Genentech/Roche, Lilly, and AstraZeneca. Several coauthors disclosed stock or ownership interests and/or other relationships with Lilly and other pharmaceutical companies. Dr. Goetz receives research funding from the National Institutes of Health. Dr. Bhave and Dr. West had no financial conflicts to disclose.

A combination of adjuvant abemaciclib and endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer, in updated results of a trial.

This was based on data collected over a median follow-up of 54 months. Previously reported data from this phase III study, known as monarchE, showed the same outcomes but over a 2-year treatment period, the researchers said.

Risk of cancer recurrence may be as much as 30% at 5 years in these high-risk patients, who will likely need more intense treatment, wrote Priya Rastogi, MD, of the University of Pittsburgh Medical Center, and colleagues.

In the new study published in the Journal of Clinical Oncology (2023 Jan 9. doi: 10.1200/JCO.23.019), the researchers reported 5-year efficacy results from an interim analysis of overall survival in the monarchE trial.

The intent-to-treat population included 2808 individuals randomized to abemaciclib plus ET and 2814 to ET alone; the median age was 51 years, and approximately 70% of the participants were White.

The addition of abemaciclib significantly reduced the risk of IDFS and DRFS over a median follow-up period of 54 months with hazard ratios of 0.680 and 0.675, respectively. Adjuvant abemaciclib also significantly improved DRFS over ET alone (HR 0.675).

The findings were limited by the lack of statistical significance for overall survival with abemaciclib. However, the increased benefits for IDFS and DRFS with abemaciclib plus ET vs. ET alone were consistent across all subgroups, and the benefit of abemaciclib was consistent regardless of the number of nodes involved, the researchers wrote.

“Prior reports from this trial with shorter follow-up demonstrated benefit of abemaciclib. However, with longer follow-up of a median 54 months, we see that the benefit of the drug is not only sustained (32% reduction in the risk of a disease event), but that there is further separation of the curves with an absolute difference in IDFS and DRFS rates of 7.6% and 6.7, comparing the ET alone vs. ET plus abemaciclib arms,” study coauthor Matthew P. Goetz, MD, said in an interview.

Although statistical significance was not reached for overall survival, fewer deaths occurred in the abemaciclib-plus-ET group compared with the ET-only group, said Dr. Goetz, of the Mayo Clinic, Rochester, Minnesota. However, patients with the worst prognosis (Ki-67–high subgroup) tended to have higher overall survival.

A total of 208 deaths occurred in the combination group vs. 234 in the ET-only group, and no new safety signals were observed. The occurrence of serious adverse events of any cause was similar in the abemaciclib group and the ET-only group (6.5% vs. 7.3%).

“These data are a pleasant surprise, as there were concerns that the benefit of the drug seen with shorter follow-up would wane over time,” Dr. Goetz said. “However, the opposite has occurred; with increasing length of follow-up, the curves continue to separate.”

Based on the new results, “we have high confidence that for patients with ER+/HER2- breast cancer at high risk of recurrence, the addition of 2 years of adjuvant abemaciclib to ET results in clinically significant improvements in IDFS,” he said.

Looking ahead, “we need additional follow-up to determine whether the benefit we now see in terms of IDFS will eventually translate into improvements in overall survival,” Dr. Goetz said. “We need to identify biomarkers that can identify patients at risk for early recurrence despite administration of adjuvant abemaciclib and further, biomarkers that will allow us to select patients that can be safely treated with ET alone.”

 

Findings Confirm Value of Combined Treatment

“It was reassuring to see the continued benefit at 5 years with adjuvant abemaciclib in combination with endocrine therapy compared to endocrine therapy alone in this high-risk HR+, HER2– EBC [early breast cancer] population,” Manali Ajay Bhave, MD, a medical oncologist at Emory University, Atlanta, said in an interview.

“While the interim overall survival analysis was not significant, further follow-up is necessary to truly discern a survival benefit particularly in this patient population where a survival advantage may not be seen for several years,” she added.

The current study supports the continued use of adjuvant abemaciclib in high-risk HR+, HER2– EBC patients, Dr. Bhave said. “Investigation of novel endocrine agents in the adjuvant setting for patients with high risk, HR+ HER2– EBC is needed to further improve outcomes.”
 

Urgent Need to Improve Adjuvant Therapy

“The monarchE study is a timely study aimed at improving adjuvant treatments in ER+ breast cancer to reduce risk of late recurrences,” Malinda T. West, MD, of the University of Wisconsin, said in an interview. “Late recurrences occurring decades later is a risk associated with ER+ breast cancer, and the risk of breast cancer recurrence is highest in those with larger tumors and nodal involvement.

“Abemaciclib is one of the three FDA-approved cyclin-dependent kinase 4/6 inhibitors in metastatic ER+ breast cancer based on demonstrated efficacy and safety in the metastatic setting compared to endocrine therapy alone, which was the rationale for expanded use of abemaciclib into the adjuvant setting for those at high risk for recurrence and basis of the monarchE trial,” said Dr. West.

An important criterion for inclusion was the randomization to abemaciclib required within 16 months of definitive breast cancer surgery, which reflected a window of time in which to start adjuvant abemaciclib, Dr. West said. “Exclusion criteria were those with a history of thromboembolic events, as abemaciclib carries a warning for venous thromboembolism,” she added.

In the monarchE follow-up, Dr. West said she was encouraged by the persistent and widening benefit with 2 years of added abemaciclib to endocrine therapy in reducing IDFS and DRFS compared to endocrine therapy alone.

Dr. West advised clinicians to consider initiating the therapy for up to 16 months after definitive breast surgery, because doing so may allow for recovery from surgery, chemotherapy, and radiation.

The findings tell physicians to “use caution with adding abemaciclib in those with a history of thromboembolic events or VTE risk factors as abemaciclib has a known VTE warning and this population was excluded in the monarchE trial,” she noted.

“Continued long-term follow up of those in this study will be important to determine survival benefits and how the predictive biomarker Ki-67 may impact survival outcomes,” she said.

The study was supported by Eli Lilly. Lead author Dr. Rastogi disclosed travel, accommodations, and expenses from Genentech/Roche, Lilly, and AstraZeneca. Several coauthors disclosed stock or ownership interests and/or other relationships with Lilly and other pharmaceutical companies. Dr. Goetz receives research funding from the National Institutes of Health. Dr. Bhave and Dr. West had no financial conflicts to disclose.

SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.

However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.

The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.

The researchers found no difference in 5-year axillary or invasive recurrence rates whether women had axillary dissections or not. The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.

Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.

“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.

However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.

Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.

So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.

Study details

The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.

Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.

Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.

Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.

Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.

The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.

The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.

The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).

Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.

“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.

The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.

SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.

However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.

The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.

The researchers found no difference in 5-year axillary or invasive recurrence rates whether women had axillary dissections or not. The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.

Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.

“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.

However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.

Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.

So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.

Study details

The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.

Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.

Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.

Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.

Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.

The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.

The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.

The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).

Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.

“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.

The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.

SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.

However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.

The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.

The researchers found no difference in 5-year axillary or invasive recurrence rates whether women had axillary dissections or not. The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.

Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.

“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.

However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.

Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.

So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.

Study details

The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.

Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.

Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.

Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.

Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.

The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.

The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.

The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).

Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.

“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.

The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.

TOPLINE:

Routine clinical examination detects only 2.2% of second breast cancers during 10-year follow-up in women undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS).

METHODOLOGY:

• National Comprehensive Cancer Network guidelines recommend DCIS surveillance with a physical exam every 6-12 months for 5 years and then annually with a mammogram every 12 months. Research, however, suggested clinical breast exams only detect 15% of second breast cancers.
• A retrospective cohort study of 1550 female members of Kaiser Permanente Northern California diagnosed with unilateral DCIS between January 1, 2008, and January 1, 2011, who were followed until 2021.
• Patients who developed a second breast cancer within 10 years of follow-up were identified from the electronic health records. The detection methods were categorized into three groups: Patient-detected, physician-detected, and imaging-detected.

TAKEAWAY:

• During follow-up, 11.5% of women developed a second breast cancer with a median time to diagnosis of 57 months. Among patients with second breast cancers, 43.0% were ipsilateral, 54.8% were contralateral, and 2.2% presented with distant metastases.
• Overall, patients had a median of five mammograms between years 1 and 6 of surveillance and a median of seven clinic visits with most providers completing a clinical examination during the visit.
• Second breast cancers were detected through imaging in 74.3% of cases compared with 20.1% detected by patients and only 2.2% detected by physicians during physical exams. The remaining 3.4% were detected incidentally from plastic surgery procedures unrelated to oncologic surveillance.
• Mammogram detected 99.2% of cases (132 of 133 cases) identified by imaging.

IN PRACTICE:

“Our findings highlight the importance of mammogram screening and patient education regarding self-detection and can inform future NCCN recommendations for DCIS survivorship care,” the authors concluded, adding that “decreasing the need for in-person breast examinations could allow for other effective methods of survivorship monitoring.”

SOURCE:

This study, led by Bethany T. Waites of Kaiser Permanente San Francisco Medical Center, San Francisco, California, was published online on December 28 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective design may have introduced selection bias or confounding. The study’s follow-up period until 2021, including the initial 18 months of the COVID-19 pandemic, may have affected surveillance patterns.

DISCLOSURES:

This study was supported by the Kaiser Permanente Northern California Graduate Medical Education program. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Routine clinical examination detects only 2.2% of second breast cancers during 10-year follow-up in women undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS).

METHODOLOGY:

• National Comprehensive Cancer Network guidelines recommend DCIS surveillance with a physical exam every 6-12 months for 5 years and then annually with a mammogram every 12 months. Research, however, suggested clinical breast exams only detect 15% of second breast cancers.
• A retrospective cohort study of 1550 female members of Kaiser Permanente Northern California diagnosed with unilateral DCIS between January 1, 2008, and January 1, 2011, who were followed until 2021.
• Patients who developed a second breast cancer within 10 years of follow-up were identified from the electronic health records. The detection methods were categorized into three groups: Patient-detected, physician-detected, and imaging-detected.

TAKEAWAY:

• During follow-up, 11.5% of women developed a second breast cancer with a median time to diagnosis of 57 months. Among patients with second breast cancers, 43.0% were ipsilateral, 54.8% were contralateral, and 2.2% presented with distant metastases.
• Overall, patients had a median of five mammograms between years 1 and 6 of surveillance and a median of seven clinic visits with most providers completing a clinical examination during the visit.
• Second breast cancers were detected through imaging in 74.3% of cases compared with 20.1% detected by patients and only 2.2% detected by physicians during physical exams. The remaining 3.4% were detected incidentally from plastic surgery procedures unrelated to oncologic surveillance.
• Mammogram detected 99.2% of cases (132 of 133 cases) identified by imaging.

IN PRACTICE:

“Our findings highlight the importance of mammogram screening and patient education regarding self-detection and can inform future NCCN recommendations for DCIS survivorship care,” the authors concluded, adding that “decreasing the need for in-person breast examinations could allow for other effective methods of survivorship monitoring.”

SOURCE:

This study, led by Bethany T. Waites of Kaiser Permanente San Francisco Medical Center, San Francisco, California, was published online on December 28 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective design may have introduced selection bias or confounding. The study’s follow-up period until 2021, including the initial 18 months of the COVID-19 pandemic, may have affected surveillance patterns.

DISCLOSURES:

This study was supported by the Kaiser Permanente Northern California Graduate Medical Education program. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Routine clinical examination detects only 2.2% of second breast cancers during 10-year follow-up in women undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS).

METHODOLOGY:

• National Comprehensive Cancer Network guidelines recommend DCIS surveillance with a physical exam every 6-12 months for 5 years and then annually with a mammogram every 12 months. Research, however, suggested clinical breast exams only detect 15% of second breast cancers.
• A retrospective cohort study of 1550 female members of Kaiser Permanente Northern California diagnosed with unilateral DCIS between January 1, 2008, and January 1, 2011, who were followed until 2021.
• Patients who developed a second breast cancer within 10 years of follow-up were identified from the electronic health records. The detection methods were categorized into three groups: Patient-detected, physician-detected, and imaging-detected.

TAKEAWAY:

• During follow-up, 11.5% of women developed a second breast cancer with a median time to diagnosis of 57 months. Among patients with second breast cancers, 43.0% were ipsilateral, 54.8% were contralateral, and 2.2% presented with distant metastases.
• Overall, patients had a median of five mammograms between years 1 and 6 of surveillance and a median of seven clinic visits with most providers completing a clinical examination during the visit.
• Second breast cancers were detected through imaging in 74.3% of cases compared with 20.1% detected by patients and only 2.2% detected by physicians during physical exams. The remaining 3.4% were detected incidentally from plastic surgery procedures unrelated to oncologic surveillance.
• Mammogram detected 99.2% of cases (132 of 133 cases) identified by imaging.

IN PRACTICE:

“Our findings highlight the importance of mammogram screening and patient education regarding self-detection and can inform future NCCN recommendations for DCIS survivorship care,” the authors concluded, adding that “decreasing the need for in-person breast examinations could allow for other effective methods of survivorship monitoring.”

SOURCE:

This study, led by Bethany T. Waites of Kaiser Permanente San Francisco Medical Center, San Francisco, California, was published online on December 28 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective design may have introduced selection bias or confounding. The study’s follow-up period until 2021, including the initial 18 months of the COVID-19 pandemic, may have affected surveillance patterns.

DISCLOSURES:

This study was supported by the Kaiser Permanente Northern California Graduate Medical Education program. The authors declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

Measuring serum hormone concentrations in postmenopausal women at high risk for developing breast cancer may help identify those most likely to benefit from preventive treatment with an aromatase inhibitor, according to findings from a case-control study using data from a large breast cancer prevention trial.

In the randomized, placebo-controlled IBIS-II prevention trial of 3864 women aged 40-70 years at increased risk for developing breast cancer, treatment with the aromatase inhibitor anastrozole was associated with a 49% reduction in breast cancer incidence. At median follow-up of 131 months, breast cancer occurred in 85 (4.4%) versus 165 (8.5%) of patients in the anastrozole and placebo arms, respectively.

A preplanned case-control study involving 212 participants from the anastrozole group (72 cases and 140 controls) and 416 from the placebo group (142 cases and 274 controls), showed a significant trend toward increasing breast cancer risk with increasing estradiol-to-sex hormone binding globulin (SHBG) ratio in the placebo group, but not in the anastrozole group (trend per quartile, 1.25 vs 1.06), reported Jack Cuzick, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues.

A weaker but still significant effect was observed for the testosterone-SHBG ratio in the placebo group (trend, 1.21), but again, no such effect was seen in the anastrozole group (trend, 1.18).

A relative benefit was seen for anastrozole in estradiol concentration quartiles 2, 3, and 4 (relative risk [RR], 0.55, 0.54, and 0.56, respectively), but not in quartile 1.

The findings were published online December 6 in The Lancet Oncology.

Study participants were recruited from 153 breast cancer treatment centers across 18 countries and randomized in a 1:1 ratio to receive 1 mg of oral anastrozole daily or placebo. For the case-control analysis, the investigators looked at the effects of baseline estradiol to SHBG ratio on the development of all breast cancers, including ductal carcinoma in situ. They also assessed the relative benefit of anastrozole versus placebo.

Case patients were those diagnosed with breast cancer after trial entry through data cutoff on October 22, 2019, and who had not used hormone replacement therapy within 3 months of trial entry or during the trial. Controls were participants without breast cancer who were randomly selected and matched according to treatment group, age, and follow-up time.

“Although the association between estradiol and breast cancer risk is well established, less is known about whether the concentrations of these hormones have an effect on the efficacy of preventive therapy with selective estrogen receptor modulators or aromatase inhibitors in women at increased risk of developing breast cancer,” the investigators noted, explaining that in the current analysis, they “tested the hypothesis that, for women with a low estradiol–SHBG ratio, anastrozole would provide little or no reduction in the risk of breast cancer.”

The results from the placebo group “confirm the increasing risk of breast cancer associated with higher estradiol and testosterone concentrations, and a decreasing risk associated with increasing SHBG concentrations in women who were not randomly allocated to receive anastrozole,” they said.

“However, to our knowledge, this is the first report of the effect of low concentrations of estradiol or testosterone on a lack of response to aromatase inhibitor treatment, either as a preventive measure or in the adjuvant setting,” they added. “These data provide support for the hypothesis that preventive therapy with an aromatase inhibitor is likely to be most effective for women with higher estradiol-to-SHBG ratios and, conversely, of little or no benefit for those with low estradiol-to-SHBG ratios.”

Thus, measurement of estradiol and SHBG concentrations might be helpful in making decisions about using inhibitors both for treatment and prevention, they continued, underscoring the importance of using assays sensitive enough to measure low estradiol concentrations in the plasma in postmenopausal women.

“We used a very sensitive liquid chromatography–tandem mass spectroscopy assay (lower limit of sensitivity of 3 pmol/L), which allowed us to accurately measure the low concentrations of estradiol and SHBG in the serum samples from our population of postmenopausal women. Wider use of this type of assay or a similar assay will be necessary to implement any of the actions suggested by this study,” they explained.

The findings “suggest a potential role for measuring estradiol, testosterone, and SHBG more widely, both in determining which individuals are at high risk and the likely response to endocrine treatment,” they concluded, noting that measuring serum hormones is inexpensive and, if used more routinely in high-risk clinics and for treatment of early breast cancer, could “substantially improve disease management.”

This study was funded by Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. Dr. Cuzick reported receiving royalties from Cancer Research UK for commercial use of the IBIS (Tyrer-Cuzick) breast cancer risk evaluation software.

Measuring serum hormone concentrations in postmenopausal women at high risk for developing breast cancer may help identify those most likely to benefit from preventive treatment with an aromatase inhibitor, according to findings from a case-control study using data from a large breast cancer prevention trial.

In the randomized, placebo-controlled IBIS-II prevention trial of 3864 women aged 40-70 years at increased risk for developing breast cancer, treatment with the aromatase inhibitor anastrozole was associated with a 49% reduction in breast cancer incidence. At median follow-up of 131 months, breast cancer occurred in 85 (4.4%) versus 165 (8.5%) of patients in the anastrozole and placebo arms, respectively.

A preplanned case-control study involving 212 participants from the anastrozole group (72 cases and 140 controls) and 416 from the placebo group (142 cases and 274 controls), showed a significant trend toward increasing breast cancer risk with increasing estradiol-to-sex hormone binding globulin (SHBG) ratio in the placebo group, but not in the anastrozole group (trend per quartile, 1.25 vs 1.06), reported Jack Cuzick, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues.

A weaker but still significant effect was observed for the testosterone-SHBG ratio in the placebo group (trend, 1.21), but again, no such effect was seen in the anastrozole group (trend, 1.18).

A relative benefit was seen for anastrozole in estradiol concentration quartiles 2, 3, and 4 (relative risk [RR], 0.55, 0.54, and 0.56, respectively), but not in quartile 1.

The findings were published online December 6 in The Lancet Oncology.

Study participants were recruited from 153 breast cancer treatment centers across 18 countries and randomized in a 1:1 ratio to receive 1 mg of oral anastrozole daily or placebo. For the case-control analysis, the investigators looked at the effects of baseline estradiol to SHBG ratio on the development of all breast cancers, including ductal carcinoma in situ. They also assessed the relative benefit of anastrozole versus placebo.

Case patients were those diagnosed with breast cancer after trial entry through data cutoff on October 22, 2019, and who had not used hormone replacement therapy within 3 months of trial entry or during the trial. Controls were participants without breast cancer who were randomly selected and matched according to treatment group, age, and follow-up time.

“Although the association between estradiol and breast cancer risk is well established, less is known about whether the concentrations of these hormones have an effect on the efficacy of preventive therapy with selective estrogen receptor modulators or aromatase inhibitors in women at increased risk of developing breast cancer,” the investigators noted, explaining that in the current analysis, they “tested the hypothesis that, for women with a low estradiol–SHBG ratio, anastrozole would provide little or no reduction in the risk of breast cancer.”

The results from the placebo group “confirm the increasing risk of breast cancer associated with higher estradiol and testosterone concentrations, and a decreasing risk associated with increasing SHBG concentrations in women who were not randomly allocated to receive anastrozole,” they said.

“However, to our knowledge, this is the first report of the effect of low concentrations of estradiol or testosterone on a lack of response to aromatase inhibitor treatment, either as a preventive measure or in the adjuvant setting,” they added. “These data provide support for the hypothesis that preventive therapy with an aromatase inhibitor is likely to be most effective for women with higher estradiol-to-SHBG ratios and, conversely, of little or no benefit for those with low estradiol-to-SHBG ratios.”

Thus, measurement of estradiol and SHBG concentrations might be helpful in making decisions about using inhibitors both for treatment and prevention, they continued, underscoring the importance of using assays sensitive enough to measure low estradiol concentrations in the plasma in postmenopausal women.

“We used a very sensitive liquid chromatography–tandem mass spectroscopy assay (lower limit of sensitivity of 3 pmol/L), which allowed us to accurately measure the low concentrations of estradiol and SHBG in the serum samples from our population of postmenopausal women. Wider use of this type of assay or a similar assay will be necessary to implement any of the actions suggested by this study,” they explained.

The findings “suggest a potential role for measuring estradiol, testosterone, and SHBG more widely, both in determining which individuals are at high risk and the likely response to endocrine treatment,” they concluded, noting that measuring serum hormones is inexpensive and, if used more routinely in high-risk clinics and for treatment of early breast cancer, could “substantially improve disease management.”

This study was funded by Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. Dr. Cuzick reported receiving royalties from Cancer Research UK for commercial use of the IBIS (Tyrer-Cuzick) breast cancer risk evaluation software.

Measuring serum hormone concentrations in postmenopausal women at high risk for developing breast cancer may help identify those most likely to benefit from preventive treatment with an aromatase inhibitor, according to findings from a case-control study using data from a large breast cancer prevention trial.

In the randomized, placebo-controlled IBIS-II prevention trial of 3864 women aged 40-70 years at increased risk for developing breast cancer, treatment with the aromatase inhibitor anastrozole was associated with a 49% reduction in breast cancer incidence. At median follow-up of 131 months, breast cancer occurred in 85 (4.4%) versus 165 (8.5%) of patients in the anastrozole and placebo arms, respectively.

A preplanned case-control study involving 212 participants from the anastrozole group (72 cases and 140 controls) and 416 from the placebo group (142 cases and 274 controls), showed a significant trend toward increasing breast cancer risk with increasing estradiol-to-sex hormone binding globulin (SHBG) ratio in the placebo group, but not in the anastrozole group (trend per quartile, 1.25 vs 1.06), reported Jack Cuzick, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues.

A weaker but still significant effect was observed for the testosterone-SHBG ratio in the placebo group (trend, 1.21), but again, no such effect was seen in the anastrozole group (trend, 1.18).

A relative benefit was seen for anastrozole in estradiol concentration quartiles 2, 3, and 4 (relative risk [RR], 0.55, 0.54, and 0.56, respectively), but not in quartile 1.

The findings were published online December 6 in The Lancet Oncology.

Study participants were recruited from 153 breast cancer treatment centers across 18 countries and randomized in a 1:1 ratio to receive 1 mg of oral anastrozole daily or placebo. For the case-control analysis, the investigators looked at the effects of baseline estradiol to SHBG ratio on the development of all breast cancers, including ductal carcinoma in situ. They also assessed the relative benefit of anastrozole versus placebo.

Case patients were those diagnosed with breast cancer after trial entry through data cutoff on October 22, 2019, and who had not used hormone replacement therapy within 3 months of trial entry or during the trial. Controls were participants without breast cancer who were randomly selected and matched according to treatment group, age, and follow-up time.

“Although the association between estradiol and breast cancer risk is well established, less is known about whether the concentrations of these hormones have an effect on the efficacy of preventive therapy with selective estrogen receptor modulators or aromatase inhibitors in women at increased risk of developing breast cancer,” the investigators noted, explaining that in the current analysis, they “tested the hypothesis that, for women with a low estradiol–SHBG ratio, anastrozole would provide little or no reduction in the risk of breast cancer.”

The results from the placebo group “confirm the increasing risk of breast cancer associated with higher estradiol and testosterone concentrations, and a decreasing risk associated with increasing SHBG concentrations in women who were not randomly allocated to receive anastrozole,” they said.

“However, to our knowledge, this is the first report of the effect of low concentrations of estradiol or testosterone on a lack of response to aromatase inhibitor treatment, either as a preventive measure or in the adjuvant setting,” they added. “These data provide support for the hypothesis that preventive therapy with an aromatase inhibitor is likely to be most effective for women with higher estradiol-to-SHBG ratios and, conversely, of little or no benefit for those with low estradiol-to-SHBG ratios.”

Thus, measurement of estradiol and SHBG concentrations might be helpful in making decisions about using inhibitors both for treatment and prevention, they continued, underscoring the importance of using assays sensitive enough to measure low estradiol concentrations in the plasma in postmenopausal women.

“We used a very sensitive liquid chromatography–tandem mass spectroscopy assay (lower limit of sensitivity of 3 pmol/L), which allowed us to accurately measure the low concentrations of estradiol and SHBG in the serum samples from our population of postmenopausal women. Wider use of this type of assay or a similar assay will be necessary to implement any of the actions suggested by this study,” they explained.

The findings “suggest a potential role for measuring estradiol, testosterone, and SHBG more widely, both in determining which individuals are at high risk and the likely response to endocrine treatment,” they concluded, noting that measuring serum hormones is inexpensive and, if used more routinely in high-risk clinics and for treatment of early breast cancer, could “substantially improve disease management.”

This study was funded by Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. Dr. Cuzick reported receiving royalties from Cancer Research UK for commercial use of the IBIS (Tyrer-Cuzick) breast cancer risk evaluation software.

manali-bhave.jpg

Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023. 

A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD. 

TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy

Study synopsis

Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial. 

Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results: 

• In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)

• At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent

• In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients

• In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively

• At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd

The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.

EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging

Study synopsis

The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study. 

Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate. 

The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events: 

• The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)

• The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)

• The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).

• In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment

• In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus

• In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib

Regarding efficacy:

• The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively

• The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively

Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer. 

OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities

Study synopsis

OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.

Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date: 

• Grade 3 neutropenia occurred in 55% of participants

• There were no grade 4 treatment-related adverse events and no dose-limiting toxicities

• OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study

• Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages

• Investigators observed antitumor activity, including partial responses

Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation. 

Conclusions

These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.

manali-bhave.jpg

Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023. 

A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD. 

TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy

Study synopsis

Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial. 

Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results: 

• In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)

• At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent

• In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients

• In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively

• At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd

The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.

EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging

Study synopsis

The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study. 

Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate. 

The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events: 

• The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)

• The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)

• The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).

• In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment

• In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus

• In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib

Regarding efficacy:

• The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively

• The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively

Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer. 

OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities

Study synopsis

OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.

Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date: 

• Grade 3 neutropenia occurred in 55% of participants

• There were no grade 4 treatment-related adverse events and no dose-limiting toxicities

• OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study

• Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages

• Investigators observed antitumor activity, including partial responses

Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation. 

Conclusions

These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.

manali-bhave.jpg

Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023. 

A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD. 

TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy

Study synopsis

Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial. 

Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results: 

• In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)

• At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent

• In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients

• In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively

• At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd

The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.

EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging

Study synopsis

The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study. 

Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate. 

The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events: 

• The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)

• The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)

• The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).

• In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment

• In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus

• In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib

Regarding efficacy:

• The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively

• The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively

Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer. 

OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities

Study synopsis

OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.

Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date: 

• Grade 3 neutropenia occurred in 55% of participants

• There were no grade 4 treatment-related adverse events and no dose-limiting toxicities

• OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study

• Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages

• Investigators observed antitumor activity, including partial responses

Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation. 

Conclusions

These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.

SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.

Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.

However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life. 

Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.

Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.

Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.

Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.

At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).

There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).

However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.

Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.

The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).

Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.

Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.

Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.

“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said. 

The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.

Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.

However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life. 

Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.

Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.

Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.

Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.

At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).

There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).

However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.

Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.

The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).

Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.

Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.

Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.

“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said. 

The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.

Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.

However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life. 

Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.

Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.

Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.

Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.

At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).

There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).

However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.

Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.

The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).

Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.

Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.

Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.

“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said. 

The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.

As with other breast cancers, we can now say to BRCA carriers: “Don’t worry. You can get pregnant. You’ll be okay,” said Jame Abraham, MD, chair of Hematology & Medical Oncology at the Cleveland Clinic, who was not involved in the research. 

The analysis, presented at the San Antonio Breast Cancer Symposium, revealed no issue with women becoming pregnant and carrying a healthy baby to term and reported no sign of worse disease outcomes among BRCA carriers following diagnosis and treatment. 

“The final and most important conclusion from our study is that conceiving after proper breast cancer treatment and follow-up should not be contraindicated anymore in young BRCA carriers,” a message of particular importance for oncofertility counseling, lead investigator Matteo Lambertini, MD, a breast cancer oncologist at the University of Genova, Italy, said during his SABCS presentation. 

The study was published December 7 in JAMA to coincide with his presentation.

Although pregnancy after breast cancer is generally considered safe, limited data exist for BRCA carriers in particular, Dr. Lambertini said.

The current analysis represents the largest look into the matter to date. The study included 4732 young women from across the globe who had been diagnosed with stage I-III invasive breast cancer. These women, all BRCA carriers, were 40 years or younger (median age at diagnosis, 35 years).

The team compared outcomes between 659 patients who had at least one pregnancy over a median follow-up of almost 8 years with 4073 women who did not become pregnant. 

Dr. Lambertini and colleagues reported a median time of 3.5 years from breast cancer diagnosis to conception. Overall, about 1 in 5 young BRCA carriers (22%) conceived within 10 years after their breast cancer diagnosis. Of the 80% of patients with a completed pregnancy, 91% delivered at term and only 4 infants (0.9%) had documented congenital anomalies.

In short, “the rate of pregnancy, fetal, and obstetric complications was low and in line with the expectations in a population of women with similar age and no history of breast cancer,” Dr. Lambertini said. The team cautioned, however, that the data was extracted from oncology medical records, which might have underreported maternal and fetal outcomes. 

Disease-free survival was similar among women who became pregnant and those who did not after breast cancer (adjusted HR, 0.99; 95% CI, 0.81-1.20). 

When looking at the specific BRCA gene, differences did emerge. BRCA1 carriers had better disease-free survival after pregnancy (aHR, 0.80), while BRCA2 carriers appeared to have worse disease-free survival after pregnancy (aHR, 1.55). 

For reasons that remain unclear, the researchers also found that BRCA1 carriers who got pregnant had significantly better breast cancer-specific survival (aHR, 0.59; P < .01) and overall survival (aHR, 0.58; P < .01). These women tended to have HR-negative breast cancer, which the authors also found was associated with improved survival after pregnancy (aHR, 0.76).

It’s possible, the team posited, that hormone receptor status played a role in the observed survival benefit. It’s also possible that these women were healthier overall. 

The overall survival advantage, however, did not extend to BRCA2 carriers, who tended to have hormone receptor-positive disease. Hormone receptor-positive status did not appear to have a significant impact on survival (aHR, 1.30; 95% CI, 0.95-1.76).

“While the results appear reassuring for BRCA1 carriers, more caution is needed to counsel BRCA2 carriers, “ the investigators wrote.

The study was funded by the Italian Association for Cancer Research, Gilead, and others. Investigators had numerous ties to industry, including Dr. Lambertini, who is an adviser and speaker for Roche, Pfizer, Novartis, and others. The full list of disclosures can be found with the original article.

A version of this article appeared on Medscape.com.

SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.

As with other breast cancers, we can now say to BRCA carriers: “Don’t worry. You can get pregnant. You’ll be okay,” said Jame Abraham, MD, chair of Hematology & Medical Oncology at the Cleveland Clinic, who was not involved in the research. 

The analysis, presented at the San Antonio Breast Cancer Symposium, revealed no issue with women becoming pregnant and carrying a healthy baby to term and reported no sign of worse disease outcomes among BRCA carriers following diagnosis and treatment. 

“The final and most important conclusion from our study is that conceiving after proper breast cancer treatment and follow-up should not be contraindicated anymore in young BRCA carriers,” a message of particular importance for oncofertility counseling, lead investigator Matteo Lambertini, MD, a breast cancer oncologist at the University of Genova, Italy, said during his SABCS presentation. 

The study was published December 7 in JAMA to coincide with his presentation.

Although pregnancy after breast cancer is generally considered safe, limited data exist for BRCA carriers in particular, Dr. Lambertini said.

The current analysis represents the largest look into the matter to date. The study included 4732 young women from across the globe who had been diagnosed with stage I-III invasive breast cancer. These women, all BRCA carriers, were 40 years or younger (median age at diagnosis, 35 years).

The team compared outcomes between 659 patients who had at least one pregnancy over a median follow-up of almost 8 years with 4073 women who did not become pregnant. 

Dr. Lambertini and colleagues reported a median time of 3.5 years from breast cancer diagnosis to conception. Overall, about 1 in 5 young BRCA carriers (22%) conceived within 10 years after their breast cancer diagnosis. Of the 80% of patients with a completed pregnancy, 91% delivered at term and only 4 infants (0.9%) had documented congenital anomalies.

In short, “the rate of pregnancy, fetal, and obstetric complications was low and in line with the expectations in a population of women with similar age and no history of breast cancer,” Dr. Lambertini said. The team cautioned, however, that the data was extracted from oncology medical records, which might have underreported maternal and fetal outcomes. 

Disease-free survival was similar among women who became pregnant and those who did not after breast cancer (adjusted HR, 0.99; 95% CI, 0.81-1.20). 

When looking at the specific BRCA gene, differences did emerge. BRCA1 carriers had better disease-free survival after pregnancy (aHR, 0.80), while BRCA2 carriers appeared to have worse disease-free survival after pregnancy (aHR, 1.55). 

For reasons that remain unclear, the researchers also found that BRCA1 carriers who got pregnant had significantly better breast cancer-specific survival (aHR, 0.59; P < .01) and overall survival (aHR, 0.58; P < .01). These women tended to have HR-negative breast cancer, which the authors also found was associated with improved survival after pregnancy (aHR, 0.76).

It’s possible, the team posited, that hormone receptor status played a role in the observed survival benefit. It’s also possible that these women were healthier overall. 

The overall survival advantage, however, did not extend to BRCA2 carriers, who tended to have hormone receptor-positive disease. Hormone receptor-positive status did not appear to have a significant impact on survival (aHR, 1.30; 95% CI, 0.95-1.76).

“While the results appear reassuring for BRCA1 carriers, more caution is needed to counsel BRCA2 carriers, “ the investigators wrote.

The study was funded by the Italian Association for Cancer Research, Gilead, and others. Investigators had numerous ties to industry, including Dr. Lambertini, who is an adviser and speaker for Roche, Pfizer, Novartis, and others. The full list of disclosures can be found with the original article.

A version of this article appeared on Medscape.com.

SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.

As with other breast cancers, we can now say to BRCA carriers: “Don’t worry. You can get pregnant. You’ll be okay,” said Jame Abraham, MD, chair of Hematology & Medical Oncology at the Cleveland Clinic, who was not involved in the research. 

The analysis, presented at the San Antonio Breast Cancer Symposium, revealed no issue with women becoming pregnant and carrying a healthy baby to term and reported no sign of worse disease outcomes among BRCA carriers following diagnosis and treatment. 

“The final and most important conclusion from our study is that conceiving after proper breast cancer treatment and follow-up should not be contraindicated anymore in young BRCA carriers,” a message of particular importance for oncofertility counseling, lead investigator Matteo Lambertini, MD, a breast cancer oncologist at the University of Genova, Italy, said during his SABCS presentation. 

The study was published December 7 in JAMA to coincide with his presentation.

Although pregnancy after breast cancer is generally considered safe, limited data exist for BRCA carriers in particular, Dr. Lambertini said.

The current analysis represents the largest look into the matter to date. The study included 4732 young women from across the globe who had been diagnosed with stage I-III invasive breast cancer. These women, all BRCA carriers, were 40 years or younger (median age at diagnosis, 35 years).

The team compared outcomes between 659 patients who had at least one pregnancy over a median follow-up of almost 8 years with 4073 women who did not become pregnant. 

Dr. Lambertini and colleagues reported a median time of 3.5 years from breast cancer diagnosis to conception. Overall, about 1 in 5 young BRCA carriers (22%) conceived within 10 years after their breast cancer diagnosis. Of the 80% of patients with a completed pregnancy, 91% delivered at term and only 4 infants (0.9%) had documented congenital anomalies.

In short, “the rate of pregnancy, fetal, and obstetric complications was low and in line with the expectations in a population of women with similar age and no history of breast cancer,” Dr. Lambertini said. The team cautioned, however, that the data was extracted from oncology medical records, which might have underreported maternal and fetal outcomes. 

Disease-free survival was similar among women who became pregnant and those who did not after breast cancer (adjusted HR, 0.99; 95% CI, 0.81-1.20). 

When looking at the specific BRCA gene, differences did emerge. BRCA1 carriers had better disease-free survival after pregnancy (aHR, 0.80), while BRCA2 carriers appeared to have worse disease-free survival after pregnancy (aHR, 1.55). 

For reasons that remain unclear, the researchers also found that BRCA1 carriers who got pregnant had significantly better breast cancer-specific survival (aHR, 0.59; P < .01) and overall survival (aHR, 0.58; P < .01). These women tended to have HR-negative breast cancer, which the authors also found was associated with improved survival after pregnancy (aHR, 0.76).

It’s possible, the team posited, that hormone receptor status played a role in the observed survival benefit. It’s also possible that these women were healthier overall. 

The overall survival advantage, however, did not extend to BRCA2 carriers, who tended to have hormone receptor-positive disease. Hormone receptor-positive status did not appear to have a significant impact on survival (aHR, 1.30; 95% CI, 0.95-1.76).

“While the results appear reassuring for BRCA1 carriers, more caution is needed to counsel BRCA2 carriers, “ the investigators wrote.

The study was funded by the Italian Association for Cancer Research, Gilead, and others. Investigators had numerous ties to industry, including Dr. Lambertini, who is an adviser and speaker for Roche, Pfizer, Novartis, and others. The full list of disclosures can be found with the original article.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Fertility preservation and/or assisted reproductive technologies do not increase the risk for short-term cancer recurrence in young women with early hormone receptor (HR)-positive breast cancer who pause endocrine therapy to conceive, according to new data from the POSITIVE trial.

“We believe these data are of vital importance for the oncofertility counseling of young breast cancer patients,” Hatem A. Azim Jr., MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center, Monterrey Institute of Technology, Mexico, said in a presentation at the San Antonio Breast Cancer Symposium.

As reported previously by this news organization, the primary results of the POSITIVE trial showed that interrupting endocrine therapy to allow pregnancy does not increase the risk of recurrence at 41 months follow-up. 

Yet, there is concern that use of fertility preservation or assisted reproductive technology methods — especially those that entail the use of hormones — could have harmful effects on patients with HR-positive breast cancers, Dr. Azim explained. 

To investigate, Dr. Azim and colleagues did a secondary analysis of outcomes from the POSITIVE trial, focusing on resumption of menstruation and use of fertility preservation and assisted reproductive technologies. 

Among 516 women evaluated for the menstruation analysis, two thirds were aged 35 and older and a little more than half (53%) reported amenorrhea at enrollment, “which is not surprising,” Dr. Azim said. 

“What is encouraging,” he said, is that 85% of women recovered menses within 6 months and 94% within 12 months of pausing endocrine therapy.

Among 497 evaluable participants who paused endocrine therapy to attempt pregnancy, 368 (74%) became pregnant.

Looking at time to pregnancy, there was a clear association between younger age at enrollment and shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64% in women younger than age 35 years, 54% in those aged 35-39, and 38% in those age 40-42. In a multivariable model, age < 35 was the only factor independently associated with a shorter time to pregnancy. 
 

No Harmful Impact on Breast Cancer Outcomes

Turning to fertility preservation and use of assisted reproductive technologies, roughly half of the women (51%) underwent some form of fertility preservation at breast cancer diagnosis and before trial enrollment, most commonly ovarian stimulation for embryo or oocyte cryopreservation.

After enrollment, 43% of women underwent some form of assisted reproductive technology to attempt pregnancy, most commonly ovarian stimulation for in vitro fertilization (IVF) and cryopreserved embryo transfer.

In the multivariable model, cryopreserved embryo transfer was the only assisted reproductive technology significantly associated with a greater chance of becoming pregnant, more than doubling patients’ odds (odds ratio, 2.4).

“This means that at breast cancer diagnosis, we should consider cryopreservation of embryos for future use if desired,” Dr. Azim said. 

Again, age mattered. Women younger than 35 undergoing assisted reproductive technologies had a 50% higher chance of becoming pregnant compared with peers aged 35-39, and an 84% higher chance than women aged 40-42. 

Importantly, there was no apparent short-term detrimental impact of fertility preservation and/or assisted reproductive technologies on breast cancer outcomes, Dr. Azim reported. At 3 years, the breast cancer-free interval was almost identical between women who underwent ovarian stimulation for cryopreservation and those who did not (9.7% vs 8.7%).

“POSITIVE showed positive results that emphasize the importance of active oncofertility counseling with the patient starting at diagnosis,” said Hee Jeong Kim, MD, PhD, professor, Division of Breast Surgery, Asan Medical Center, Seoul, Republic of Korea, and discussant for the study. 

“These data are reassuring for our young patients with a diagnosis of breast cancer and shows that assisted reproductive technology is an option and is probably safe to do with the caveat that it needs longer follow-up,” added SABCS codirector Carlos Arteaga, MD, director, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas.

Dr. Azim has no relevant disclosures. Dr. Arteaga is a scientific adviser to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, PUMA Biotechnology, TAIHO Oncology, Sanofi, and the Susan G. Komen Foundation. He has received grant support from Pfizer, Lilly, and Takeda. Dr. Kim reports no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Fertility preservation and/or assisted reproductive technologies do not increase the risk for short-term cancer recurrence in young women with early hormone receptor (HR)-positive breast cancer who pause endocrine therapy to conceive, according to new data from the POSITIVE trial.

“We believe these data are of vital importance for the oncofertility counseling of young breast cancer patients,” Hatem A. Azim Jr., MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center, Monterrey Institute of Technology, Mexico, said in a presentation at the San Antonio Breast Cancer Symposium.

As reported previously by this news organization, the primary results of the POSITIVE trial showed that interrupting endocrine therapy to allow pregnancy does not increase the risk of recurrence at 41 months follow-up. 

Yet, there is concern that use of fertility preservation or assisted reproductive technology methods — especially those that entail the use of hormones — could have harmful effects on patients with HR-positive breast cancers, Dr. Azim explained. 

To investigate, Dr. Azim and colleagues did a secondary analysis of outcomes from the POSITIVE trial, focusing on resumption of menstruation and use of fertility preservation and assisted reproductive technologies. 

Among 516 women evaluated for the menstruation analysis, two thirds were aged 35 and older and a little more than half (53%) reported amenorrhea at enrollment, “which is not surprising,” Dr. Azim said. 

“What is encouraging,” he said, is that 85% of women recovered menses within 6 months and 94% within 12 months of pausing endocrine therapy.

Among 497 evaluable participants who paused endocrine therapy to attempt pregnancy, 368 (74%) became pregnant.

Looking at time to pregnancy, there was a clear association between younger age at enrollment and shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64% in women younger than age 35 years, 54% in those aged 35-39, and 38% in those age 40-42. In a multivariable model, age < 35 was the only factor independently associated with a shorter time to pregnancy. 
 

No Harmful Impact on Breast Cancer Outcomes

Turning to fertility preservation and use of assisted reproductive technologies, roughly half of the women (51%) underwent some form of fertility preservation at breast cancer diagnosis and before trial enrollment, most commonly ovarian stimulation for embryo or oocyte cryopreservation.

After enrollment, 43% of women underwent some form of assisted reproductive technology to attempt pregnancy, most commonly ovarian stimulation for in vitro fertilization (IVF) and cryopreserved embryo transfer.

In the multivariable model, cryopreserved embryo transfer was the only assisted reproductive technology significantly associated with a greater chance of becoming pregnant, more than doubling patients’ odds (odds ratio, 2.4).

“This means that at breast cancer diagnosis, we should consider cryopreservation of embryos for future use if desired,” Dr. Azim said. 

Again, age mattered. Women younger than 35 undergoing assisted reproductive technologies had a 50% higher chance of becoming pregnant compared with peers aged 35-39, and an 84% higher chance than women aged 40-42. 

Importantly, there was no apparent short-term detrimental impact of fertility preservation and/or assisted reproductive technologies on breast cancer outcomes, Dr. Azim reported. At 3 years, the breast cancer-free interval was almost identical between women who underwent ovarian stimulation for cryopreservation and those who did not (9.7% vs 8.7%).

“POSITIVE showed positive results that emphasize the importance of active oncofertility counseling with the patient starting at diagnosis,” said Hee Jeong Kim, MD, PhD, professor, Division of Breast Surgery, Asan Medical Center, Seoul, Republic of Korea, and discussant for the study. 

“These data are reassuring for our young patients with a diagnosis of breast cancer and shows that assisted reproductive technology is an option and is probably safe to do with the caveat that it needs longer follow-up,” added SABCS codirector Carlos Arteaga, MD, director, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas.

Dr. Azim has no relevant disclosures. Dr. Arteaga is a scientific adviser to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, PUMA Biotechnology, TAIHO Oncology, Sanofi, and the Susan G. Komen Foundation. He has received grant support from Pfizer, Lilly, and Takeda. Dr. Kim reports no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Fertility preservation and/or assisted reproductive technologies do not increase the risk for short-term cancer recurrence in young women with early hormone receptor (HR)-positive breast cancer who pause endocrine therapy to conceive, according to new data from the POSITIVE trial.

“We believe these data are of vital importance for the oncofertility counseling of young breast cancer patients,” Hatem A. Azim Jr., MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center, Monterrey Institute of Technology, Mexico, said in a presentation at the San Antonio Breast Cancer Symposium.

As reported previously by this news organization, the primary results of the POSITIVE trial showed that interrupting endocrine therapy to allow pregnancy does not increase the risk of recurrence at 41 months follow-up. 

Yet, there is concern that use of fertility preservation or assisted reproductive technology methods — especially those that entail the use of hormones — could have harmful effects on patients with HR-positive breast cancers, Dr. Azim explained. 

To investigate, Dr. Azim and colleagues did a secondary analysis of outcomes from the POSITIVE trial, focusing on resumption of menstruation and use of fertility preservation and assisted reproductive technologies. 

Among 516 women evaluated for the menstruation analysis, two thirds were aged 35 and older and a little more than half (53%) reported amenorrhea at enrollment, “which is not surprising,” Dr. Azim said. 

“What is encouraging,” he said, is that 85% of women recovered menses within 6 months and 94% within 12 months of pausing endocrine therapy.

Among 497 evaluable participants who paused endocrine therapy to attempt pregnancy, 368 (74%) became pregnant.

Looking at time to pregnancy, there was a clear association between younger age at enrollment and shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64% in women younger than age 35 years, 54% in those aged 35-39, and 38% in those age 40-42. In a multivariable model, age < 35 was the only factor independently associated with a shorter time to pregnancy. 
 

No Harmful Impact on Breast Cancer Outcomes

Turning to fertility preservation and use of assisted reproductive technologies, roughly half of the women (51%) underwent some form of fertility preservation at breast cancer diagnosis and before trial enrollment, most commonly ovarian stimulation for embryo or oocyte cryopreservation.

After enrollment, 43% of women underwent some form of assisted reproductive technology to attempt pregnancy, most commonly ovarian stimulation for in vitro fertilization (IVF) and cryopreserved embryo transfer.

In the multivariable model, cryopreserved embryo transfer was the only assisted reproductive technology significantly associated with a greater chance of becoming pregnant, more than doubling patients’ odds (odds ratio, 2.4).

“This means that at breast cancer diagnosis, we should consider cryopreservation of embryos for future use if desired,” Dr. Azim said. 

Again, age mattered. Women younger than 35 undergoing assisted reproductive technologies had a 50% higher chance of becoming pregnant compared with peers aged 35-39, and an 84% higher chance than women aged 40-42. 

Importantly, there was no apparent short-term detrimental impact of fertility preservation and/or assisted reproductive technologies on breast cancer outcomes, Dr. Azim reported. At 3 years, the breast cancer-free interval was almost identical between women who underwent ovarian stimulation for cryopreservation and those who did not (9.7% vs 8.7%).

“POSITIVE showed positive results that emphasize the importance of active oncofertility counseling with the patient starting at diagnosis,” said Hee Jeong Kim, MD, PhD, professor, Division of Breast Surgery, Asan Medical Center, Seoul, Republic of Korea, and discussant for the study. 

“These data are reassuring for our young patients with a diagnosis of breast cancer and shows that assisted reproductive technology is an option and is probably safe to do with the caveat that it needs longer follow-up,” added SABCS codirector Carlos Arteaga, MD, director, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas.

Dr. Azim has no relevant disclosures. Dr. Arteaga is a scientific adviser to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, PUMA Biotechnology, TAIHO Oncology, Sanofi, and the Susan G. Komen Foundation. He has received grant support from Pfizer, Lilly, and Takeda. Dr. Kim reports no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.