Cancer

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

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

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

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

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

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

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

The U.S. Multi-Society Task Force on Colorectal Cancer (CRC) has lowered the recommended age to start CRC screening from 50 to 45 years of age for all average-risk individuals.

Although no studies have directly demonstrated the result of lowering the age of screening, lead author Swati G. Patel, MD, of University of Colorado Anschutz Medical Center, Aurora, and colleagues suggested that the increasing incidence of advanced CRC among younger individuals, coupled with the net benefit of screening, warrant a lower age threshold.

“Recent data ... show that CRC incidence rates in individuals ages 50 to 64 have increased by 1% annually between 2011 and 2016,” the authors wrote in Gastroenterology. “Similarly, CRC incidence and mortality rates in persons under age 50, termed early-age onset CRC (EAO-CRC), are also increasing.”

The task force of nine experts, representing the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, conducted a literature review and generated recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition to recommending a lower age for initial screening, Dr. Patel and colleagues provided guidance for cessation of screening among older individuals.
 

Guidance for screening initiation

According to the authors, the present risk of CRC among younger individuals mirrors the historical risk for older individuals before screening was prevalent.

“The current CRC incidence rates in individuals ages 45 to 49 are similar to the incidence rates observed in 50-year-olds in 1992, before widespread CRC screening was performed,” they wrote.

Elevated rates among younger people have been disproportionately driven by rectal cancer, according to the authors. From 2006 to 2015, incidence of rectal cancer among Americans under 50 increased 1.7% per year, compared with 0.7% per year for colon cancer, based on data from the North American Association of Central Cancer Registries.

Associated mortality rates also increased, the authors noted. From 1999-2019, mortality from colon cancer among people 45-49 years increased from 6.4 to 6.6 deaths per 100,000 individuals, while deaths from rectal cancer increased from 1.3 to 1.7 per 100,000, according to the CDC. Concurrently, CRC-associated mortality rates among older individuals generally declined.

While these findings suggest a growing disease burden among the under-50-year age group, controlled data demonstrating the effects of earlier screening are lacking, Dr. Patel and colleagues noted. Still, they predicted that expanded screening would generate a net benefit.

“Although there are no CRC screening safety data for average-risk individuals [younger than] 50, there are ample data that colonoscopy for other indications (screening based on family history, symptom evaluation, etc.) is safer when comparing younger versus older individuals,” they wrote.

Supporting this claim, the authors cited three independently generated microsimulation models from the Agency for Healthcare Research and Quality that “showed a favorable balance of life-years gained compared with adverse events,” given 100% compliance.
 

Guidance for screening cessation

Like the situation with younger individuals, minimal data are available to determine the best time for screening cessation, according to the task force.

“There are no randomized or observational studies after 2017 that enrolled individuals over age 75 to inform the appropriate time to stop CRC screening,” the authors wrote. “In our search of 37 relevant articles, only one presented primary data for when to stop screening.”

This one available study showed that some individuals older than 74 do in fact gain benefit from screening,

“For example,” Dr. Patel and colleagues wrote, “women without a history of screening and no comorbidities benefitted from annual fecal immunochemical test (FIT) screening until age 90, whereas unscreened men with or without comorbidities benefited from annual FIT screening until age 88. Conversely, screening was not beneficial beyond age 66 in men or women with severe comorbidities.”

The task force therefore recommended personalized screening for individuals 76-85 years of age “based on the balance of benefits and harms and individual patient clinical factors and preferences.”

Screening for individuals 86 years and older, according to the task force, is unnecessary.

The authors disclosed relationships with Olympus America, Bayer Pharmaceuticals, Janssen Pharmaceuticals, and others.

This article was updated on Jan. 3, 2022.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – In a large prospective, international cohort, food additive nitrates and nitrites, artificial sweeteners (especially aspartame and acesulfame-K), and dietary trans fatty acids were found to be associated with increased cancer risks.

The findings were reported in three poster presentations (P1-09-01, P1-09-02 and P3-12-35) at the 2021 San Antonio Breast Cancer Symposium from the ongoing French NutriNet-Santé web-based study of 171,000 people that was launched in France in 2009 to investigate nutrition and health relationships. The authors of the analyses note that while evidence of deleterious health effects has been established for the dietary focus of their studies, and cancer risks have been suspected, strong evidence of a cancer association has been lacking.

Nitrates and nitrites are used in processed meats to increase shelf life and to avoid bacterial growth, said Eloi Chazelas, PhD, Nutritional Epidemiology Research Team (EREN) at Sorbonne Paris Nord University. Dr. Chazelas looked at consumption of nitrites and nitrates through repeated 24 hour dietary records, linked to a comprehensive food composition database. The study’s main outcome measure was adjusted associations between nitrite and nitrate exposures and the risk of cancer (overall and by main cancer sites).

During follow-up, 966 breast and 400 prostate cancers were diagnosed among 3,311 first incident cancer cases. Breast cancer risk was elevated (HR = 1.24 [1.03-1.48], P = 0.02) among higher consumers of nitrates from food additives, especially with potassium nitrate consumption (HR = 1.25 [1.04-1.50], P = 0.01). Elevated prostate cancer risk was associated with nitrites (HR = 1.58 [1.14-2.18], P = 0.008), specifically for sodium nitrite (HR = 1.62 [1.17-2.25], P = 0.004). Nitrates and nitrites from natural sources were not associated significantly with higher cancer risk, Dr. Chazelas said.

He and his team found that food additive nitrates were positively associated with breast cancer risk, and food additive nitrites were positively associated with prostate cancer risk. “While these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of nitrite additives in the food industry,” said Dr. Chazelas, who is a doctoral candidate at Sorbonne Paris Nord University.

In “Breast and prostate cancer risk associated with nitrites and nitrates from food additives (P1-09-01),” the study included 102,046 adults from the French NutriNet-Santé prospective cohort (2009-2021). It examined associations between artificial sweetener intakes (total from all dietary sources, the most frequently consumed ones [aspartame e951, acesulfame-K e950 and sucralose e955]) and cancer risk (overall and by sites: breast, prostate and obesity-related cancers).

Overall cancer risk in people who consumed higher amounts of total sweeteners (i.e. above the median exposure in consumers) was elevated (n = 2,527 cases, hazard ratio = 1.12, 95 percent confidence interval = 1.00-1.25, P-trend=0.005), especially for aspartame (HR = 1.20 [1.05-1.38] P = 0.001) and acesulfame-K (HR = 1.18 [1.04-1.34] P = 0.003). Elevated breast cancer risks (among 723 cases) were observed for total sweeteners (HR = 1.25 [1.02-1.53] P = 0.01), for aspartame (HR = 1.33 [1.05-1.69] P = 0.007), and for acesulfame-K (HR = 1.39 [1.11-1.74] P = 0.003). Also, obesity-related cancers (1,509 cases) were increased for total sweeteners (HR = 1.16 [1.00-1.33] P = 0.02), for aspartame (HR = 1.22 [1.02-1.45] P = 0.01) and for acesulfame-K (HR = 1.23 [1.04-1.45] P = 0.01).

Artificial sweeteners are found in more than 10,000 foods and beverages, said Charlotte Debras, a doctoral candidate in nutritional epidemiology at Sorbonne Paris Nord University. “These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally,” she said.
 

Trans fatty acid intakes and cancer risk

Investigating associations between trans fatty acid intake (total ruminant [rTFAs], industrial [iTFAs], and corresponding specific isomers and cancer risk), the analysis of Gaëlle Wendeu-Foyet, PhD, Sorbonne Paris Nord University, found a total of 3,374 incident cancer cases (982 breast, 405 prostate) in an overall population of 104,909. Dietary intake of total TFAs was associated with higher prostate cancer risk (hazard ration for quartile 4 versus 1: 1.27, 1.11-1.77 P-trend = 0.005). Also, rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 P-trend = 0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 P-trend = 0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 P-trend = 0.01; CLA: 1.29, 1.00-1.66 P-trend = 0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 P-trend = 0.02; CLA: 2.013, 1.25-3.23 P-trend = 0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 P-trend = 0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 P-trend = 0.01; hexadecenoic acid: 1.28, 1.05-1.56 P-trend = 0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 P-trend = 0.07) cancer risks.

“These results support the WHO’s goal of achieving elimination from food supplies of industrially produced TFAs,” Dr. Foyet said. “The consumption of food products containing partially hydrogenated oils should be avoided.”

Nutrition, along with avoiding tobacco intake, is one of the main modifiable risk factors for chronic diseases. “There is a lot at stake in terms of prevention. This requires a combination of actions at the individual level to the public level by informing the public through food labeling,” Ms. Debras said.

It also requires influencing the context in which citizens evolve by encouraging manufacturers to improve their products (pricing policies, commitment charters for product reformulation, etc.), and limiting advertising and marketing for products of poor nutritional quality (especially among children),” she said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

SAN ANTONIO – Breast cancer survivors with chronic musculoskeletal pain may experience relief from pain with electroacupuncture and auricular acupuncture, according to a new study recently presented at the 2021 San Antonio Breast Cancer Symposium.

Both techniques led to clinically meaningful and persistent reduction of pain, but electroacupuncture was more effective in reducing pain severity, according to study author Wanqing Iris Zhi, MD, PhD, of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center in New York.

Among breast cancer survivors, Dr. Zhi said, chronic musculoskeletal pain is common and debilitating. In earlier results of the PEACE (Personalized Electroacupuncture versus Auricular Acupuncture Comparative Effectiveness) trial, both electroacupuncture and auricular acupuncture improved pain control better than usual care in cancer survivors. The comparative effectiveness between electroacupuncture and auricular acupuncture among breast cancer survivors, specifically for chronic musculoskeletal pain, remains unknown.

To evaluate potential differences between electroacupuncture and auricular acupuncture, Dr. Zhi et al. examined data from PEACE, a three-arm, parallel, single center randomized trial investigating electroacupuncture and auricular acupuncture for chronic musculoskeletal pain, compared with usual care. Among 360 cancer survivors in PEACE, mean age in 165 cancer survivors with a primary diagnosis of breast cancer was 60.3 years (35.8 percent non-White) with a mean of 5.4 years since their cancer diagnoses. Patients in both the electroacupuncture and auricular acupuncture groups received 10 weekly treatments. Change in mean Brief Pain Inventory (BPI) pain severity from baseline to week 12 was the primary endpoint, with BPI change to week 24 as a secondary endpoint. Usual care patients, after week 12, could receive 10 electroacupuncture treatments.

The most common locations of chronic musculoskeletal pain, Dr. Zhi observed, were lower back (24 percent), knee/leg (24 percent) and shoulder/elbow (14 percent). About 70 percent of patients were taking pain medication. Both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reductions among the evaluated breast cancer survivors. The change in BPI severity from baseline to week 12 was –0.29 (confidence interval, –0.08, 0.28) in the UC group. In the electroacupuncture group it was –2.65 (CI, –3.06, –2.25; P ≤0.001 from baseline) and –2.37 versus usual care (CI, –3.05, –1.68; P ≤0.001 versus UC). For the auricular acupuncture group, the change from baseline was –1.75 (CI, –2.15, –1.35; P ≤0.001 from baseline) and –1.46 versus usual care (CI, –2.14, –0.78; P ≤0.001 versus UC). The difference in BPI pain severity reduction from baseline between electroacupuncture and auricular acupuncture of –0.90 (CI, –1.45, –0.36) was statistically significant (P ≤0.001). Electroacupuncture also reduced pain severity significantly more than auricular acupuncture at week 24 (CI, –0.82, [–1.38, –0.27], P = 0.004).

Dr. Zhi concluded that among breast cancer survivors, although both electroacupuncture and auricular acupuncture were associated with clinically meaningful and persistent pain reduction, electroacupuncture was more effective at reducing pain severity.

She pointed out also that neither surgery type (mastectomy versus lumpectomy; P = 0.83) nor aromatase inhibitor versus tamoxifen versus neither (P = 0.59) was associated with BPI/severity response among electroacupuncture and auricular acupuncture patients.

“Both electroacupuncture and auricular acupuncture are significantly better than usual care, so it suggests that both acupuncture methods can be utilized for treating chronic muscle skeletal pain in breast cancer survivors, but electroacupuncture is preferred,” Dr. Zhi said.

“Auricular acupuncture can be more painful,” said PEACE principal investigator Jun Mao, MD, who is chair of integrative medicine at Memorial Sloan Kettering. “Ten percent of women could not tolerate the ear pain or discomfort. Electroacupuncture is generally well tolerated. People are more relaxed after treatment. If both are available, start with electroacupuncture,” he said.

New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.

The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).

In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).

While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.

The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
 

Test prolactin levels

Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium. 

They identified 914 cases of invasive breast cancer among 540,737 women.

Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.

Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.

Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.

“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
 

A matter of debate

Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”

This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.

However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.

“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.

“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.

When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.

This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.

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

New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.

The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).

In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).

While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.

The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
 

Test prolactin levels

Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium. 

They identified 914 cases of invasive breast cancer among 540,737 women.

Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.

Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.

Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.

“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
 

A matter of debate

Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”

This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.

However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.

“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.

“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.

When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.

This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.

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

New research provides more evidence that antipsychotics that raise prolactin levels are tied to a significantly increased risk for breast cancer.

The relative risk for breast cancer was 62% higher in women who took category 1 antipsychotic medications associated with high prolactin levels. These include haloperidol (Haldol), paliperidone (Invega), and risperidone (Risperdal). Additionally, the risk was 54% higher in those taking category 2 antipsychotics that have mid-range effects on prolactin. These include iloperidone (Fanapt), lurasidone (Latuda), and olanzapine (Zyprexa).

In contrast, category 3 antipsychotics which have a lesser effect on prolactin levels were not associated with any increase in breast cancer risk. These drugs include aripiprazole (Abilify), asenapine (Saphris), brexpiprazole (Rexulti), cariprazine (Vraylar), clozapine (multiple brands), quetiapine (Seroquel), and ziprasidone (Geodon).

While the “absolute” breast cancer risk for these drugs is unclear, “we can make the case that high circulating prolactin levels are associated with breast cancer risk. This follows what is already known about prolactin from prior studies, notably the nurses’ health studies,” Tahir Rahman, MD, associate professor of psychiatry, Washington University School of Medicine, St. Louis, told this news organization.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr. Rahman added in a news release.

The study was published online Dec. 3 in the Journal of Clinical Psychopharmacology.
 

Test prolactin levels

Using administrative claims data, the researchers evaluated breast cancer risk in women aged 18-64 exposed to antipsychotic medications compared with anticonvulsants and/or lithium. 

They identified 914 cases of invasive breast cancer among 540,737 women.

Roughly 52% of the study population filled at least one prescription for a category 3 antipsychotic agent, whereas 15% filled at least one prescription for a category 1 agent; 49% of women filled at least one prescription for an anticonvulsant medication during the study period.

Exposure to all antipsychotics was independently associated with a 35% increased risk for breast cancer (adjusted hazard ratio, 1.35; 95% CI, 1.14-1.61), the study team found.

Compared with anticonvulsants or lithium, the risk for breast cancer was significantly increased for high prolactin (category 1) antipsychotics (adjusted hazard ratio, 1.62; 95% CI, 1.30-2.03) and for mid-prolactin (category 2) drugs (aHR 1.54; 95% CI, 1.19-1.99), with no increased risk for category 3 antipsychotics.

“Our research is obviously of interest for preventing breast cancer in antipsychotic-treated patients. Checking a blood prolactin level is cheap and easy [and a high level is] fairly simple to mitigate,” said Dr. Rahman.
 

A matter of debate

Reached for comment, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said, “The potential elevation of breast cancer risk depending on the dose and time of treatment with antipsychotic medications with varying degrees of prolactin-raising properties has been a topic of research and matter of debate.”

This new study “adds another data point indicating that antipsychotics that are associated on average with a higher prolactin-raising effect than other antipsychotics may increase the risk of breast cancer in women to some degree,” said Dr. Correll, who was not involved with the study.

However, he cautioned that “naturalistic data are always vulnerable to residual confounding, for example, unmeasured effects that could also at least partially explain the results, and the follow-up time of only 4 years (maximum 6 years) in this study was relatively short.

“Nevertheless, given availability of many different antipsychotics with varying degrees of prolactin-raising potential, in women requiring antipsychotic treatment, less prolactin-raising antipsychotics may be preferable,” Dr. Correll said.

“In women receiving prolactin-raising antipsychotics for medium- and longer-term maintenance therapy, prolactin levels should be monitored,” he added.

When an elevated prolactin level is detected, this should be addressed “either via dose reduction, a switch to an alternative antipsychotic that does not raise prolactin levels significantly, or the addition of a partial or full D2 agonist when the prolactin-raising antipsychotic should be continued based on individualized risk assessment,” Dr. Correll advised.

This work was supported by an award from the Alvin J. Siteman Cancer Center; the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health; the Taylor Family Institute for Innovative Psychiatric Research; and the Center for Brain Research in Mood Disorders. The authors have disclosed no relevant financial relationships. Dr. Correll has received royalties from UpToDate and is a stock option holder of LB Pharma.

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

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

Black women with metastatic triple-negative breast cancer (mTNBC) have outcomes in response to the antibody–drug conjugate sacituzumab govitecan (SG) (Trodelvy, Gilead) comparable to those of the overall patient population, with the drug showing similar efficacy and safety, shows a prespecified analysis of ASCENT.

A heterogenous disease with few treatment options and poor outcomes, mTNBC has an incidence rate twice as high in Black as in White women.

Black women with mTNBC may also experience worse outcomes than other groups, with a greater risk of mortality related to disparities in access to health care and in income, delays in treatment, a higher prevalence of comorbidities, and differences in tumor biology.

Previously presented data from the phase 3 ASCENT trial showed that SG nearly doubled overall survival versus single-agent chemotherapy in pretreated women with mTNBC, with the benefit observed across patient subgroups.

Based on these findings, the Food and Drug Administration approved SG for patients with mTNBC who have received at least two prior chemotherapies, at least one of which is to have been given in the metastatic setting.

Now, an analysis of the ASCENT data in just over 60 Black women with mTNBC showed that they can expect to see their progression-free survival (PFS) improve by 56% and their overall survival increase by a nonsignificant 36% when given SG as opposed to single-agent chemotherapy.

The research (abstract P5-16-07) was presented at the San Antonio Breast Cancer Symposium on Dec. 10.

The team says that Black women with mTNBC “derived a similar clinical benefit” from SG versus chemotherapy to other women in the study, and had a “manageable” safety profile, which was “consistent with the full trial population.”

Consequently, SG “should be considered a treatment option for Black patients with mTNBC who have received ≥ 2 prior chemotherapies,” at least one of which having been given in the metastatic setting.

Lead researcher Lisa A. Carey, MD, told this news organiztion that it is “very important” to show that the drug works in Black patients, adding: “We know that certain drugs don’t perform so well and it’s also true that people of color are particularly affected by TNBC.”

She said there were “only 62” Black patients in ASCENT, “so if you look at the entire trial and make assumptions that the drug performs the same in all the subsets, then sometimes you’re wrong.”

Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said there is “emerging interest” in racial disparities in cancer outcomes.

“Black patients have more trouble with access to care,” she said, noting that “in trial populations, [the outcomes] generally seem similar because the patients who go onto the trials tend to be those that can participate, but you never know until you look.”

Overall, Dr. Carey said the current results suggest that, “at least from the standpoint of the therapeutic implications of this drug – which is really a pretty remarkable drug in the overall study – it behaves very similarly in this group.”

Jennifer K. Litton, MD, vice president of clinical research at University of Texas MD Anderson Cancer Center, Houston, said: “We have known that minority patients, especially Black patients, have a higher rate of triple negative breast cancer and aggressive biologies, and have had worse breast cancer outcomes in many published series.”

She told this news organization that, “additionally, they are often underrepresented in breast cancer clinical trials.”

Dr. Litton said “the very favorable outcomes” reported in “this important subset of patients who participated in the ASCENT trial” confirm the use of SG in patients with mTNBC.

To examine the clinical outcomes of Black patients in the ASCENT study, the team conduced a prespecified analysis of participants self-reporting Black race who had been randomized to SG or single-agent chemotherapy of physician’s choice, including those with and without brain metastases.

Of the 529 patients enrolled to ASCENT, 62 (12%) were Black, of whom 28 were assigned to SG and 34 to single agent chemotherapy. The two groups were generally well balanced, although six patients in the chemotherapy arm had known brain metastases at baseline versus none of those given SG.

After a median treatment duration of 5.3 months with SG and 1.6 months for single-agent chemotherapy, there was a significant improvement in PFS with SG, at 5.4 months versus 2.2 months for chemotherapy, and a hazard ratio of 0.44 (P = .008).

There was also a nonsignificant improvement in overall survival with SG at 13.8 months versus 8.5 months for chemotherapy, and a hazard ratio of 0.64 (P = .159).

The objective response rate was 32% with SG versus 6% in patients given chemotherapy, while the median duration of response was 9.2 months in the SG arm and not evaluable for chemotherapy.

The researchers note that these efficacy findings were “consistent” with those seen in the full ASCENT study population.

In terms of safety, the most common treatment-related adverse events were neutropenia, seen in 64% of SG and 61% of chemotherapy patients, diarrhea in 64% and 13%, respectively, and fatigue, in 52% and 39%, respectively.

The most common grade ≥3 events were neutropenia, in 48% and 42% of SG and chemotherapy patients, respectively, followed by anemia, in 12% and 6%, respectively, leukopenia in 8% and 16%, respectively, and febrile neutropenia in 8% and 3%, respectively.

No treatment-related deaths occurred in either treatment arm.

Dose reduction due to treatment-emergent adverse events was recorded in 28% of patients receiving SG and 35% of those assigned to single-agent chemotherapy, and discontinuations occurred in 0% and 3%, respectively.

The study was sponsored by Gilead Sciences. Dr. Carey reports research funding from Sanofi, Novartis, Genentech/Roche, and GSK; spouse serves on the board of Falcon Therapeutics.

SAN ANTONIO – A small study suggests the frequent use of antibiotics among women with triple-negative breast cancer, may have an impact on overall and breast cancer–specific mortality.

The study was recently presented at the San Antonio Breast Cancer Symposium by Julia D. Ransohoff, MD, of Stanford (Calif.) University.

Gut-associated lymphoid tissues are the largest component of the immune system. They influence both local and systemic immune responses, but the use of antimicrobials can decrease circulating and tumor-infiltrating lymphocytes that effect the immune repertoire and in turn, the survival of women with triple-negative breast cancer.

Dr. Ransohoff and colleagues hypothesized that increasing antimicrobial exposure in the presence of time-varying absolute lymphocyte counts may lead to higher overall and breast cancer–specific mortality. Their analysis is based on data from the population-based Surveillance, Epidemiology, and End Results registry and electronic medical records from Stanford University and Sutter Health. It included 772 women who were treated for triple-negative breast cancer between 2000 and 2014. The women were followed for an average of 104 months.

In an earlier analysis of this same group, Dr. Ransohoff found that higher minimum absolute lymphocyte counts were associated with lower overall mortality (hazard ratio, 0.23; 95% confidence interval, 0.16-0.35) and breast cancer mortality (HR, 0.19; 95% CI, 0.11-0.34) The association between higher peripheral lymphocyte counts and tumor-infiltrating lymphocytes was significant.

In the analysis of relationships between antibiotic use and mortality, 85% of women (n = 654) were prescribed antibiotics after having been diagnosed with triple-negative breast cancer. The death rate among patients who were prescribed antibiotics was 23% (153/654), compared with 20% (24/118) among the patients who were not treated with antibiotics (which accounts for 15% of the entire group).

For total antibiotic exposure, the HR for overall mortality was 1.06 (95% CI, 1.03-1.09; P < .001) and 1.07 for breast cancer–specific mortality (95% CI, 1.04-1.10; P < .001). For unique antibiotic exposure (not counting repeat prescriptions of the same antibiotic), the HR for overall mortality was 1.17 (95% CI, 1.12-1.22; P < .001) and 1.18 for breast cancer–specific mortality (95% CI, 1.12-1.24; P < .001). 

“These were all statistically significant associations derived from a statistical model that takes into account baseline patient characteristics, so the reported hazard ratios, to the best of our ability, represent the risk of death associated with antibiotic use adjusted for other baseline covariates. We’ve attempted to account for differences at baseline that may indicate patients are sicker, and so the reported risk represents mortality related with antibiotic exposure,” Dr. Ransohoff said.

Elucidating the role of the microbiome in mediating absolute lymphocyte counts and immune response may inform interventions to reduce triple-negative mortality, she said.

SAN ANTONIO – A small study suggests the frequent use of antibiotics among women with triple-negative breast cancer, may have an impact on overall and breast cancer–specific mortality.

The study was recently presented at the San Antonio Breast Cancer Symposium by Julia D. Ransohoff, MD, of Stanford (Calif.) University.

Gut-associated lymphoid tissues are the largest component of the immune system. They influence both local and systemic immune responses, but the use of antimicrobials can decrease circulating and tumor-infiltrating lymphocytes that effect the immune repertoire and in turn, the survival of women with triple-negative breast cancer.

Dr. Ransohoff and colleagues hypothesized that increasing antimicrobial exposure in the presence of time-varying absolute lymphocyte counts may lead to higher overall and breast cancer–specific mortality. Their analysis is based on data from the population-based Surveillance, Epidemiology, and End Results registry and electronic medical records from Stanford University and Sutter Health. It included 772 women who were treated for triple-negative breast cancer between 2000 and 2014. The women were followed for an average of 104 months.

In an earlier analysis of this same group, Dr. Ransohoff found that higher minimum absolute lymphocyte counts were associated with lower overall mortality (hazard ratio, 0.23; 95% confidence interval, 0.16-0.35) and breast cancer mortality (HR, 0.19; 95% CI, 0.11-0.34) The association between higher peripheral lymphocyte counts and tumor-infiltrating lymphocytes was significant.

In the analysis of relationships between antibiotic use and mortality, 85% of women (n = 654) were prescribed antibiotics after having been diagnosed with triple-negative breast cancer. The death rate among patients who were prescribed antibiotics was 23% (153/654), compared with 20% (24/118) among the patients who were not treated with antibiotics (which accounts for 15% of the entire group).

For total antibiotic exposure, the HR for overall mortality was 1.06 (95% CI, 1.03-1.09; P < .001) and 1.07 for breast cancer–specific mortality (95% CI, 1.04-1.10; P < .001). For unique antibiotic exposure (not counting repeat prescriptions of the same antibiotic), the HR for overall mortality was 1.17 (95% CI, 1.12-1.22; P < .001) and 1.18 for breast cancer–specific mortality (95% CI, 1.12-1.24; P < .001). 

“These were all statistically significant associations derived from a statistical model that takes into account baseline patient characteristics, so the reported hazard ratios, to the best of our ability, represent the risk of death associated with antibiotic use adjusted for other baseline covariates. We’ve attempted to account for differences at baseline that may indicate patients are sicker, and so the reported risk represents mortality related with antibiotic exposure,” Dr. Ransohoff said.

Elucidating the role of the microbiome in mediating absolute lymphocyte counts and immune response may inform interventions to reduce triple-negative mortality, she said.

SAN ANTONIO – A small study suggests the frequent use of antibiotics among women with triple-negative breast cancer, may have an impact on overall and breast cancer–specific mortality.

The study was recently presented at the San Antonio Breast Cancer Symposium by Julia D. Ransohoff, MD, of Stanford (Calif.) University.

Gut-associated lymphoid tissues are the largest component of the immune system. They influence both local and systemic immune responses, but the use of antimicrobials can decrease circulating and tumor-infiltrating lymphocytes that effect the immune repertoire and in turn, the survival of women with triple-negative breast cancer.

Dr. Ransohoff and colleagues hypothesized that increasing antimicrobial exposure in the presence of time-varying absolute lymphocyte counts may lead to higher overall and breast cancer–specific mortality. Their analysis is based on data from the population-based Surveillance, Epidemiology, and End Results registry and electronic medical records from Stanford University and Sutter Health. It included 772 women who were treated for triple-negative breast cancer between 2000 and 2014. The women were followed for an average of 104 months.

In an earlier analysis of this same group, Dr. Ransohoff found that higher minimum absolute lymphocyte counts were associated with lower overall mortality (hazard ratio, 0.23; 95% confidence interval, 0.16-0.35) and breast cancer mortality (HR, 0.19; 95% CI, 0.11-0.34) The association between higher peripheral lymphocyte counts and tumor-infiltrating lymphocytes was significant.

In the analysis of relationships between antibiotic use and mortality, 85% of women (n = 654) were prescribed antibiotics after having been diagnosed with triple-negative breast cancer. The death rate among patients who were prescribed antibiotics was 23% (153/654), compared with 20% (24/118) among the patients who were not treated with antibiotics (which accounts for 15% of the entire group).

For total antibiotic exposure, the HR for overall mortality was 1.06 (95% CI, 1.03-1.09; P < .001) and 1.07 for breast cancer–specific mortality (95% CI, 1.04-1.10; P < .001). For unique antibiotic exposure (not counting repeat prescriptions of the same antibiotic), the HR for overall mortality was 1.17 (95% CI, 1.12-1.22; P < .001) and 1.18 for breast cancer–specific mortality (95% CI, 1.12-1.24; P < .001). 

“These were all statistically significant associations derived from a statistical model that takes into account baseline patient characteristics, so the reported hazard ratios, to the best of our ability, represent the risk of death associated with antibiotic use adjusted for other baseline covariates. We’ve attempted to account for differences at baseline that may indicate patients are sicker, and so the reported risk represents mortality related with antibiotic exposure,” Dr. Ransohoff said.

Elucidating the role of the microbiome in mediating absolute lymphocyte counts and immune response may inform interventions to reduce triple-negative mortality, she said.

SAN ANTONIO – Sedative-hypnotic medications, such as benzodiazepines and nonbenzodiazepine sedative-hypnotics commonly used to treat chemotherapy-related nausea, anxiety, and insomnia in women being treated for breast cancer, put women at high risk of dependency after chemotherapy treatment, shows a new study.

While benzodiazepines and nonbenzodiazepine sedative-hypnotics are effective for these indications, misuse and increased health care utilization can ensue from their prolonged use, said Jacob C. Cogan, MD, a fellow in oncology/hematology at the Herbert Irving Comprehensive Cancer Center, Columbia University, New York. Dr. Cogan recently presented the results of the study at the San Antonio Breast Cancer Symposium.

The study included patients with breast cancer who received adjuvant chemotherapy between 2008 and 2017. Prescriptions for sedatives were divided into three periods: 365 days prior to chemotherapy to the start of chemotherapy (period one); start of chemotherapy to 90 days after the end of chemotherapy (period two); and 90-365 days after chemotherapy (period three). Patients who filled at least one benzodiazepine prescription in period two and patients who filled at least two benzodiazepine in period three were classified as new persistent benzodiazepine users. The same definitions were then used for nonbenzodiazepine sedative-hypnotics.

Among 17,532 benzodiazepine-naive patients (mean age, 57 years) and 21,863 nonbenzodiazepine sedative-hypnotic drug–naive patients (mean age, 56 years) who received adjuvant chemotherapy for breast cancer, lumpectomies were performed for a small majority (56.6% benzodiazepine naive, 55.1% nonbenzodiazepine sedative-hypnotics naive) versus mastectomy, and about half of patients received less than 4 months of chemotherapy (48.0% benzodiazepine naive, 48.6% nonbenzodiazepine sedative-hypnotics naive). Among benzodiazepine-naive patients, 4,447 (25.4%) filled at least one benzodiazepine prescription during chemotherapy, and 2,160 (9.9%) filled at least one nonbenzodiazepine sedative-hypnotic prescription during chemotherapy. The rate of new persistent benzodiazepine use after initial exposure during chemotherapy was 26.8% (n = 1,192). Similarly, 33.8% (n = 730) of nonbenzodiazepine sedative-hypnotics users became new persistent users. In addition, 115 patients became new persistent users of both types of sedative-hypnotics.

New persistent benzodiazepine use was associated with several characteristics: age 50-65 (odds ratio, 1.23; P = .01) and age greater than 65 (OR, 1.38, P = .005) relative to age less than 49; as well as Medicaid insurance, relative to commercial and Medicare insurance (OR, 1.68; P < .0001). Both new persistent benzodiazepine and nonbenzodiazepine sedative-hypnotics use was associated with chemotherapy duration of less than 4 months relative to 4 or more months of chemotherapy (OR, 1.17; P = .03 for benzodiazepines; OR, 1.58; P < .0001 for nonbenzodiazepine sedative-hypnotics).

It is not clear why shorter chemotherapy duration is associated with more new persistent use, Dr. Cogan said. “It may be that, paradoxically, a shorter duration of treatment could lead to more anxiety about recurrence. These patients may need closer monitoring of mental health symptoms and earlier referral for psychological services.”

Dr. Cogan said that providers should take steps to ensure that benzodiazepines and nonbenzodiazepine sedatives are used appropriately, which includes tapering dosages and, when appropriate, encouraging nonpharmacologic strategies.

There were no funding or other conflicts of interest associated with this study.

SAN ANTONIO – Sedative-hypnotic medications, such as benzodiazepines and nonbenzodiazepine sedative-hypnotics commonly used to treat chemotherapy-related nausea, anxiety, and insomnia in women being treated for breast cancer, put women at high risk of dependency after chemotherapy treatment, shows a new study.

While benzodiazepines and nonbenzodiazepine sedative-hypnotics are effective for these indications, misuse and increased health care utilization can ensue from their prolonged use, said Jacob C. Cogan, MD, a fellow in oncology/hematology at the Herbert Irving Comprehensive Cancer Center, Columbia University, New York. Dr. Cogan recently presented the results of the study at the San Antonio Breast Cancer Symposium.

The study included patients with breast cancer who received adjuvant chemotherapy between 2008 and 2017. Prescriptions for sedatives were divided into three periods: 365 days prior to chemotherapy to the start of chemotherapy (period one); start of chemotherapy to 90 days after the end of chemotherapy (period two); and 90-365 days after chemotherapy (period three). Patients who filled at least one benzodiazepine prescription in period two and patients who filled at least two benzodiazepine in period three were classified as new persistent benzodiazepine users. The same definitions were then used for nonbenzodiazepine sedative-hypnotics.

Among 17,532 benzodiazepine-naive patients (mean age, 57 years) and 21,863 nonbenzodiazepine sedative-hypnotic drug–naive patients (mean age, 56 years) who received adjuvant chemotherapy for breast cancer, lumpectomies were performed for a small majority (56.6% benzodiazepine naive, 55.1% nonbenzodiazepine sedative-hypnotics naive) versus mastectomy, and about half of patients received less than 4 months of chemotherapy (48.0% benzodiazepine naive, 48.6% nonbenzodiazepine sedative-hypnotics naive). Among benzodiazepine-naive patients, 4,447 (25.4%) filled at least one benzodiazepine prescription during chemotherapy, and 2,160 (9.9%) filled at least one nonbenzodiazepine sedative-hypnotic prescription during chemotherapy. The rate of new persistent benzodiazepine use after initial exposure during chemotherapy was 26.8% (n = 1,192). Similarly, 33.8% (n = 730) of nonbenzodiazepine sedative-hypnotics users became new persistent users. In addition, 115 patients became new persistent users of both types of sedative-hypnotics.

New persistent benzodiazepine use was associated with several characteristics: age 50-65 (odds ratio, 1.23; P = .01) and age greater than 65 (OR, 1.38, P = .005) relative to age less than 49; as well as Medicaid insurance, relative to commercial and Medicare insurance (OR, 1.68; P < .0001). Both new persistent benzodiazepine and nonbenzodiazepine sedative-hypnotics use was associated with chemotherapy duration of less than 4 months relative to 4 or more months of chemotherapy (OR, 1.17; P = .03 for benzodiazepines; OR, 1.58; P < .0001 for nonbenzodiazepine sedative-hypnotics).

It is not clear why shorter chemotherapy duration is associated with more new persistent use, Dr. Cogan said. “It may be that, paradoxically, a shorter duration of treatment could lead to more anxiety about recurrence. These patients may need closer monitoring of mental health symptoms and earlier referral for psychological services.”

Dr. Cogan said that providers should take steps to ensure that benzodiazepines and nonbenzodiazepine sedatives are used appropriately, which includes tapering dosages and, when appropriate, encouraging nonpharmacologic strategies.

There were no funding or other conflicts of interest associated with this study.

SAN ANTONIO – Sedative-hypnotic medications, such as benzodiazepines and nonbenzodiazepine sedative-hypnotics commonly used to treat chemotherapy-related nausea, anxiety, and insomnia in women being treated for breast cancer, put women at high risk of dependency after chemotherapy treatment, shows a new study.

While benzodiazepines and nonbenzodiazepine sedative-hypnotics are effective for these indications, misuse and increased health care utilization can ensue from their prolonged use, said Jacob C. Cogan, MD, a fellow in oncology/hematology at the Herbert Irving Comprehensive Cancer Center, Columbia University, New York. Dr. Cogan recently presented the results of the study at the San Antonio Breast Cancer Symposium.

The study included patients with breast cancer who received adjuvant chemotherapy between 2008 and 2017. Prescriptions for sedatives were divided into three periods: 365 days prior to chemotherapy to the start of chemotherapy (period one); start of chemotherapy to 90 days after the end of chemotherapy (period two); and 90-365 days after chemotherapy (period three). Patients who filled at least one benzodiazepine prescription in period two and patients who filled at least two benzodiazepine in period three were classified as new persistent benzodiazepine users. The same definitions were then used for nonbenzodiazepine sedative-hypnotics.

Among 17,532 benzodiazepine-naive patients (mean age, 57 years) and 21,863 nonbenzodiazepine sedative-hypnotic drug–naive patients (mean age, 56 years) who received adjuvant chemotherapy for breast cancer, lumpectomies were performed for a small majority (56.6% benzodiazepine naive, 55.1% nonbenzodiazepine sedative-hypnotics naive) versus mastectomy, and about half of patients received less than 4 months of chemotherapy (48.0% benzodiazepine naive, 48.6% nonbenzodiazepine sedative-hypnotics naive). Among benzodiazepine-naive patients, 4,447 (25.4%) filled at least one benzodiazepine prescription during chemotherapy, and 2,160 (9.9%) filled at least one nonbenzodiazepine sedative-hypnotic prescription during chemotherapy. The rate of new persistent benzodiazepine use after initial exposure during chemotherapy was 26.8% (n = 1,192). Similarly, 33.8% (n = 730) of nonbenzodiazepine sedative-hypnotics users became new persistent users. In addition, 115 patients became new persistent users of both types of sedative-hypnotics.

New persistent benzodiazepine use was associated with several characteristics: age 50-65 (odds ratio, 1.23; P = .01) and age greater than 65 (OR, 1.38, P = .005) relative to age less than 49; as well as Medicaid insurance, relative to commercial and Medicare insurance (OR, 1.68; P < .0001). Both new persistent benzodiazepine and nonbenzodiazepine sedative-hypnotics use was associated with chemotherapy duration of less than 4 months relative to 4 or more months of chemotherapy (OR, 1.17; P = .03 for benzodiazepines; OR, 1.58; P < .0001 for nonbenzodiazepine sedative-hypnotics).

It is not clear why shorter chemotherapy duration is associated with more new persistent use, Dr. Cogan said. “It may be that, paradoxically, a shorter duration of treatment could lead to more anxiety about recurrence. These patients may need closer monitoring of mental health symptoms and earlier referral for psychological services.”

Dr. Cogan said that providers should take steps to ensure that benzodiazepines and nonbenzodiazepine sedatives are used appropriately, which includes tapering dosages and, when appropriate, encouraging nonpharmacologic strategies.

There were no funding or other conflicts of interest associated with this study.

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease.

The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease. 

Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”

In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).

The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.

“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.

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

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease.

The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease. 

Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”

In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).

The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.

“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.

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

The Food and Drug Administration has approved pembrolizumab (Keytruda) for the adjuvant treatment of stage IIB and IIC melanoma after complete resection in adults and children over age 12 years. The FDA also extended the approval to those with stage III disease.

The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease. 

Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”

In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.

After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).

The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.

“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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

Genomic profiling improves outcomes for patients with metastatic breast cancer as long as the alteration-drug match has good clinical trial evidence supporting its use, a new pooled analysis suggests.

“The message is very simple,” lead study author Fabrice Andre, MD, PhD, research director, Gustave Roussy Cancer Campus, Villejuif, France, told this news organization during a virtual press briefing. “If a genomic alteration is validated, it is useful to give targeted therapy, but if the genomic alteration is not validated, we should not give a targeted therapy.”

The study, which pooled results from phase 2 randomized trials SAFIR02-BREAST and SAFIR-P13K, was presented Dec. 7 in a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

The new analysis explored two key questions: Is genomic testing of a cancer effective? And how should oncologists interpret a genomic report?

A total of 1,462 patients with metastatic HER2-negative breast cancer underwent next-generation sequencing. After receiving six to eight cycles of chemotherapy, 238 patients (16%) were randomized to one of nine targeted therapies matched to the genomic alteration identified on testing or to maintenance chemotherapy.

Genomic alterations in the patients’ tumors were classified using the ESMO Scale of Actionability of Molecular Targets (ESCAT). A tier I ranking indicates that the alteration-drug match is associated with improved outcomes in clinical trials, while a tier II ranking means that the alteration-drug match is associated with antitumor activity but the magnitude of benefit remains unknown.

In an analysis of the overall trial population, Dr. Andre and colleagues found an improvement in progression-free survival in the targeted therapy group (median of 5.5 months) in comparison with the maintenance chemotherapy group (2.9 months), but the difference was not significant (P = .109).

In a subgroup of 115 patients presenting with I- or II-tier genomic alterations, median progression-free survival was 59% longer, at 9.1 months, among patients receiving targeted therapy, compared with 2.8 months in the maintenance chemotherapy group (hazard ratio, 0.41; P < .001).

In addition, the team carried out single-nucleotide polymorphism (SNP) array analyses on 926 patients. They identified 21 genes that were altered more frequently in the metastases compared with the primary tumors, and they observed that a high homologous recombination deficiency score in patients with BCRA 1 or 2 mutations was associated with a longer progression-free survival in patients treated with olaparib.

“We also identified a subset of patients who are resistant to CDK4/6 inhibitors who presented with CDK4 amplification, and this amplification is associated with overexpression,” Dr. Andre explained.

When asked whether most oncologists were using genomic profiling to tailor treatment for breast cancer patients, Dr. Andre said that multigene sequencing is now widely used.

“The issue is not so much whether we should use or not use genomics; the issue here is to force everyone to put the genomic alteration in the right context in terms of its level of evidence,” Dr. Andre told this news organization.

Oncologists may overinterpret the genomic activation identified and give a targeted therapy that is not validated, but “oncologists should not use genomic information when the target has not been previously validated in a therapeutic trial,” he added.

Virginia Kaklamani, MD, professor of medicine at the University of Texas Health Sciences Center in San Antonio, said in an interview that approximately 5 years ago, Dr. Andre was part of the first debate at the SABCS discussing whether oncologists should be conducting next-generation sequencing for their patients with breast cancer.

“At the time, [Dr.] Andre’s comment was that we should not be doing it,” recalled Dr. Kaklamani, who is also leader of the breast cancer program at the Mays Cancer Center at the University of Texas Health San Antonio MD Anderson. “At that point, I think it was clear that we did not have the data we needed to be able to use next-generation sequencing to change our clinical management.”

However, the evidence has evolved. “Based on this clinical trial, I think we now do have the data,” she said. “I think that [next-generation sequencing] is something we will be using more and more in practice and treating our patients based on [validated] genomic alterations.”

Dr. Andre has received grants or advisory board/speaker honoraria from Daiichi Sankyo, Roche, Pfizer, AstraZeneca, Lily, and Novartis. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics, has received research funding from Eisai, and has served as a speaker for Pfizer, Celgene, Genentech, and Genomic Health, among other companies.

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