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Polygenic breast cancer risk scores strive to overcome racial bias
The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.
Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.
While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.
Study underscores need for ethnically diverse datasets
In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.
The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.
After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.
PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.
In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.
The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.
“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.
First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.
“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.
In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”
Higher morality among African American women
While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.
Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”
Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.
Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
Potential PRS benefits underscore need to eliminate bias
The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.
For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.
A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.
Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.
Confluence project
Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.
Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.
“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.
Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.
“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.
NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.
Direct-to-consumer global PRS
In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”
The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.
A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.
In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.
However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).
According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.
“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”
“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.
“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”
Commercial PRSs may benefit research
While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.
“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”
In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.
“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”
Dr. Pederson disclosed that she is a consultant for Myriad Genetics.
The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.
Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.
While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.
Study underscores need for ethnically diverse datasets
In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.
The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.
After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.
PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.
In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.
The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.
“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.
First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.
“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.
In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”
Higher morality among African American women
While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.
Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”
Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.
Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
Potential PRS benefits underscore need to eliminate bias
The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.
For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.
A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.
Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.
Confluence project
Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.
Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.
“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.
Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.
“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.
NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.
Direct-to-consumer global PRS
In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”
The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.
A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.
In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.
However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).
According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.
“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”
“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.
“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”
Commercial PRSs may benefit research
While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.
“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”
In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.
“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”
Dr. Pederson disclosed that she is a consultant for Myriad Genetics.
The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.
Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.
While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.
Study underscores need for ethnically diverse datasets
In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.
The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.
After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.
PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.
In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.
The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.
“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.
First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.
“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.
In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”
Higher morality among African American women
While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.
Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”
Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.
Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
Potential PRS benefits underscore need to eliminate bias
The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.
For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.
A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.
Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.
Confluence project
Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.
Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.
“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.
Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.
“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.
NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.
Direct-to-consumer global PRS
In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”
The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.
A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.
In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.
However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).
According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.
“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”
“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.
“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”
Commercial PRSs may benefit research
While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.
“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”
In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.
“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”
Dr. Pederson disclosed that she is a consultant for Myriad Genetics.
FROM JAMA NETWORK OPEN
Internal mammary lymph node radiation safe over the long term
After a median follow-up of 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques,” say investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, Belgium.
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery, and decreased doses to non-target tissues,” the team says.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers comment.
The study was published online on July 28 in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweighs the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White says the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation.”
She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy, but cardiopulmonary complications are still possible even with improved techniques, she writes.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1% without.
The incidence of any cardiac disease was 11.1% in the radiation arm, versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.
Still, “it seems logical to take the pre-existing cardiac comorbidity of patients into consideration,” the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up of 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques,” say investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, Belgium.
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery, and decreased doses to non-target tissues,” the team says.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers comment.
The study was published online on July 28 in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweighs the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White says the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation.”
She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy, but cardiopulmonary complications are still possible even with improved techniques, she writes.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1% without.
The incidence of any cardiac disease was 11.1% in the radiation arm, versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.
Still, “it seems logical to take the pre-existing cardiac comorbidity of patients into consideration,” the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up of 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques,” say investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, Belgium.
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery, and decreased doses to non-target tissues,” the team says.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers comment.
The study was published online on July 28 in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweighs the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White says the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation.”
She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy, but cardiopulmonary complications are still possible even with improved techniques, she writes.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1% without.
The incidence of any cardiac disease was 11.1% in the radiation arm, versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.
Still, “it seems logical to take the pre-existing cardiac comorbidity of patients into consideration,” the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Internal mammary lymph node radiation safe over the long term
After a median follow-up 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer–related mortality, even before introducing heart-sparing techniques,” said the investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp (Belgium).
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to nontarget tissues,” the team wrote.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers commented.
The study was published online on July 28, 2021, in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, noted in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explained. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White said the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal [IMN] radiation.”
She noted that, since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she wrote.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1%.
The incidence of any cardiac disease was 11.1% in the radiation arm versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors noted that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and colleagues noted, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer–related mortality with trials that began after 1988.
Still, “it seems logical to take the preexisting cardiac comorbidity of patients into consideration,” the investigators concluded. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer–related mortality, even before introducing heart-sparing techniques,” said the investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp (Belgium).
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to nontarget tissues,” the team wrote.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers commented.
The study was published online on July 28, 2021, in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, noted in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explained. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White said the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal [IMN] radiation.”
She noted that, since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she wrote.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1%.
The incidence of any cardiac disease was 11.1% in the radiation arm versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors noted that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and colleagues noted, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer–related mortality with trials that began after 1988.
Still, “it seems logical to take the preexisting cardiac comorbidity of patients into consideration,” the investigators concluded. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer–related mortality, even before introducing heart-sparing techniques,” said the investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp (Belgium).
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to nontarget tissues,” the team wrote.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers commented.
The study was published online on July 28, 2021, in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, noted in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explained. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White said the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal [IMN] radiation.”
She noted that, since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she wrote.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1%.
The incidence of any cardiac disease was 11.1% in the radiation arm versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors noted that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and colleagues noted, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer–related mortality with trials that began after 1988.
Still, “it seems logical to take the preexisting cardiac comorbidity of patients into consideration,” the investigators concluded. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
How many years of aromatase inhibitor therapy in breast cancer?
That’s a question that has been vexing oncologists for more than a decade, but final results from a large study now suggest that, after an initial 5 years of adjuvant endocrine therapy with tamoxifen and/or an AI, an additional 5 years of AI therapy offer no clinical benefits, compared with an additional 2 years of therapy.
What’s more, 5 years of additional treatment were associated with a significantly increased risk for fractures, compared with 2 years of therapy, Michael Gnant, MD, from the Medical University of Vienna, and colleagues reported in the phase 3 Austrian Breast and Colorectal Cancer Study Group Trial 16 (ABCSG-16).
“Thus, in postmenopausal women with hormone receptor–positive breast cancer who had received 5 years of adjuvant endocrine therapy, the extension of aromatase inhibitor therapy for 2 years rather than 5 years was sufficient to maximize the benefits of such therapy in most patients without extending the exposure to toxic effects,” they concluded.
The study was published online on July 28, 2021, in the New England Journal of Medicine.
The new results “in patients with hormone-receptor–positive breast cancer who are at low or average risk underscore the importance of avoiding iatrogenic complications when making these decisions,” Pamela J. Goodwin, MD, from the Lunenfeld–Tanenbaum Research Institute at the University of Toronto, wrote in an accompanying editorial.
She noted that these latest results echo those of two earlier studies: the DATA trial and the optimistically named IDEAL trial, both of which showed no benefit of short-term versus longer-term adjuvant endocrine therapy with regard to either disease-free survival (DFS) or overall survival (OS).
“These results provide strong evidence against the routine use of more than 2 years of extended aromatase inhibitor therapy in women who are at low or average risk, similar to those who were included in this trial,” Dr. Goodwin commented.
ABCSG-16 details
Dr. Gnant and colleagues enrolled 3,484 women aged 80 years or younger with HR-positive stage I, II, or III breast cancer for whom there was no evidence of recurrence at baseline. The patients had all received adjuvant tamoxifen or an AI for 5 years; for some patients, the two drugs were administered in sequence until 12 months before randomization.
The patients were randomly assigned to receive oral anastrozole 1 mg daily for either 2 or 5 additional years.
Among all patients, 3,208 had experienced no recurrence 2 years after randomization. These patients were included in the primary DFS analysis. Of this group, 1,635 (51%) had received tamoxifen alone for 5 years, 235 (7.3%) had received an AI alone, and 41.7% had received sequential AIs and tamoxifen.
At a median follow-up of 118 months after randomization, disease progression or death occurred in 670 women – 335 in each trial arm.
The rate of DFS 10 years after randomization was 73.6% in the 2-year additional-therapy group and 73.9% in the 5-year group. The hazard ratio for disease recurrence or death was 0.99 and was not significant. After adjustment for potential confounding factors, the HR remained essentially unchanged (HR, 1.0).
Overall survival at 8 years, a secondary endpoint, was virtually identical between the groups, at 87.5% in the 2-year group and 87.3% in the 5-year group. The HR for death from any cause was 1.02 and was not significant.
The HR for contralateral breast cancer was 1.15, and the HR for a second primary cancer was 1.06; neither was statistically significant.
Although the use of bone-targeted medication was similar between the groups, among patients in the 2-year group, the incidence of clinical bone fractures 5 years after randomization was lower, at 4.7% versus 6.3%, which translates to an HR for fracture with 5 additional years of AI therapy of 1.35 (95% confidence interval, 1.00-1.84).
Adverse events with anastrozole were consistent with its known toxicity profile. At least one serious adverse event occurred in 26.5% of patients in the 2-year group and in 40.2% in the 5-year group. Investigator-assessed serious adverse events that were judged to be related to anastrozole occurred in 2.3% and 4.0% of patients, respectively.
Osteoarthritis, the most frequently reported adverse event, was documented in 1.7% of patients in the 2-year group and in 4.3% in the 5-year group.
AI duration still unclear
“We did not investigate the value of extending adjuvant endocrine therapy per se, since the benefit of extending aromatase inhibitors after 5 years of adjuvant tamoxifen has been well established. In contrast, the most effective duration of adjuvant aromatase inhibitor therapy remains unclear in randomized trials,” Dr. Gnant and colleagues commented.
In her editorial, Dr. Goodwin summarized potential approaches for improving late outcomes for patients with hormone receptor–positive breast cancers, including the use of biomarkers to detect minimal residual disease and therapies to treat it.
She noted that the detection of circulating tumor cells in patients with HR-positive breast cancer 5 years after diagnosis is associated with a 13-fold increase in risk for recurrence and a median time to clinical recurrence of 2.8 years.
“This interval may be sufficiently long that therapeutic intervention can prevent the development of incurable clinical metastases. Continued improvement in these assays and the development of new therapies that target the unique biologic features of dormant cells will no doubt be required for a major reduction in late recurrence risk,” she wrote.
The study was supported by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group. Dr. Gnant has received lecture fees from AstraZeneca and others. Dr. Goodwin has received institutional research funding from the Breast Cancer Research Foundation and EPIC Sciences.
A version of this article first appeared on Medscape.com.
That’s a question that has been vexing oncologists for more than a decade, but final results from a large study now suggest that, after an initial 5 years of adjuvant endocrine therapy with tamoxifen and/or an AI, an additional 5 years of AI therapy offer no clinical benefits, compared with an additional 2 years of therapy.
What’s more, 5 years of additional treatment were associated with a significantly increased risk for fractures, compared with 2 years of therapy, Michael Gnant, MD, from the Medical University of Vienna, and colleagues reported in the phase 3 Austrian Breast and Colorectal Cancer Study Group Trial 16 (ABCSG-16).
“Thus, in postmenopausal women with hormone receptor–positive breast cancer who had received 5 years of adjuvant endocrine therapy, the extension of aromatase inhibitor therapy for 2 years rather than 5 years was sufficient to maximize the benefits of such therapy in most patients without extending the exposure to toxic effects,” they concluded.
The study was published online on July 28, 2021, in the New England Journal of Medicine.
The new results “in patients with hormone-receptor–positive breast cancer who are at low or average risk underscore the importance of avoiding iatrogenic complications when making these decisions,” Pamela J. Goodwin, MD, from the Lunenfeld–Tanenbaum Research Institute at the University of Toronto, wrote in an accompanying editorial.
She noted that these latest results echo those of two earlier studies: the DATA trial and the optimistically named IDEAL trial, both of which showed no benefit of short-term versus longer-term adjuvant endocrine therapy with regard to either disease-free survival (DFS) or overall survival (OS).
“These results provide strong evidence against the routine use of more than 2 years of extended aromatase inhibitor therapy in women who are at low or average risk, similar to those who were included in this trial,” Dr. Goodwin commented.
ABCSG-16 details
Dr. Gnant and colleagues enrolled 3,484 women aged 80 years or younger with HR-positive stage I, II, or III breast cancer for whom there was no evidence of recurrence at baseline. The patients had all received adjuvant tamoxifen or an AI for 5 years; for some patients, the two drugs were administered in sequence until 12 months before randomization.
The patients were randomly assigned to receive oral anastrozole 1 mg daily for either 2 or 5 additional years.
Among all patients, 3,208 had experienced no recurrence 2 years after randomization. These patients were included in the primary DFS analysis. Of this group, 1,635 (51%) had received tamoxifen alone for 5 years, 235 (7.3%) had received an AI alone, and 41.7% had received sequential AIs and tamoxifen.
At a median follow-up of 118 months after randomization, disease progression or death occurred in 670 women – 335 in each trial arm.
The rate of DFS 10 years after randomization was 73.6% in the 2-year additional-therapy group and 73.9% in the 5-year group. The hazard ratio for disease recurrence or death was 0.99 and was not significant. After adjustment for potential confounding factors, the HR remained essentially unchanged (HR, 1.0).
Overall survival at 8 years, a secondary endpoint, was virtually identical between the groups, at 87.5% in the 2-year group and 87.3% in the 5-year group. The HR for death from any cause was 1.02 and was not significant.
The HR for contralateral breast cancer was 1.15, and the HR for a second primary cancer was 1.06; neither was statistically significant.
Although the use of bone-targeted medication was similar between the groups, among patients in the 2-year group, the incidence of clinical bone fractures 5 years after randomization was lower, at 4.7% versus 6.3%, which translates to an HR for fracture with 5 additional years of AI therapy of 1.35 (95% confidence interval, 1.00-1.84).
Adverse events with anastrozole were consistent with its known toxicity profile. At least one serious adverse event occurred in 26.5% of patients in the 2-year group and in 40.2% in the 5-year group. Investigator-assessed serious adverse events that were judged to be related to anastrozole occurred in 2.3% and 4.0% of patients, respectively.
Osteoarthritis, the most frequently reported adverse event, was documented in 1.7% of patients in the 2-year group and in 4.3% in the 5-year group.
AI duration still unclear
“We did not investigate the value of extending adjuvant endocrine therapy per se, since the benefit of extending aromatase inhibitors after 5 years of adjuvant tamoxifen has been well established. In contrast, the most effective duration of adjuvant aromatase inhibitor therapy remains unclear in randomized trials,” Dr. Gnant and colleagues commented.
In her editorial, Dr. Goodwin summarized potential approaches for improving late outcomes for patients with hormone receptor–positive breast cancers, including the use of biomarkers to detect minimal residual disease and therapies to treat it.
She noted that the detection of circulating tumor cells in patients with HR-positive breast cancer 5 years after diagnosis is associated with a 13-fold increase in risk for recurrence and a median time to clinical recurrence of 2.8 years.
“This interval may be sufficiently long that therapeutic intervention can prevent the development of incurable clinical metastases. Continued improvement in these assays and the development of new therapies that target the unique biologic features of dormant cells will no doubt be required for a major reduction in late recurrence risk,” she wrote.
The study was supported by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group. Dr. Gnant has received lecture fees from AstraZeneca and others. Dr. Goodwin has received institutional research funding from the Breast Cancer Research Foundation and EPIC Sciences.
A version of this article first appeared on Medscape.com.
That’s a question that has been vexing oncologists for more than a decade, but final results from a large study now suggest that, after an initial 5 years of adjuvant endocrine therapy with tamoxifen and/or an AI, an additional 5 years of AI therapy offer no clinical benefits, compared with an additional 2 years of therapy.
What’s more, 5 years of additional treatment were associated with a significantly increased risk for fractures, compared with 2 years of therapy, Michael Gnant, MD, from the Medical University of Vienna, and colleagues reported in the phase 3 Austrian Breast and Colorectal Cancer Study Group Trial 16 (ABCSG-16).
“Thus, in postmenopausal women with hormone receptor–positive breast cancer who had received 5 years of adjuvant endocrine therapy, the extension of aromatase inhibitor therapy for 2 years rather than 5 years was sufficient to maximize the benefits of such therapy in most patients without extending the exposure to toxic effects,” they concluded.
The study was published online on July 28, 2021, in the New England Journal of Medicine.
The new results “in patients with hormone-receptor–positive breast cancer who are at low or average risk underscore the importance of avoiding iatrogenic complications when making these decisions,” Pamela J. Goodwin, MD, from the Lunenfeld–Tanenbaum Research Institute at the University of Toronto, wrote in an accompanying editorial.
She noted that these latest results echo those of two earlier studies: the DATA trial and the optimistically named IDEAL trial, both of which showed no benefit of short-term versus longer-term adjuvant endocrine therapy with regard to either disease-free survival (DFS) or overall survival (OS).
“These results provide strong evidence against the routine use of more than 2 years of extended aromatase inhibitor therapy in women who are at low or average risk, similar to those who were included in this trial,” Dr. Goodwin commented.
ABCSG-16 details
Dr. Gnant and colleagues enrolled 3,484 women aged 80 years or younger with HR-positive stage I, II, or III breast cancer for whom there was no evidence of recurrence at baseline. The patients had all received adjuvant tamoxifen or an AI for 5 years; for some patients, the two drugs were administered in sequence until 12 months before randomization.
The patients were randomly assigned to receive oral anastrozole 1 mg daily for either 2 or 5 additional years.
Among all patients, 3,208 had experienced no recurrence 2 years after randomization. These patients were included in the primary DFS analysis. Of this group, 1,635 (51%) had received tamoxifen alone for 5 years, 235 (7.3%) had received an AI alone, and 41.7% had received sequential AIs and tamoxifen.
At a median follow-up of 118 months after randomization, disease progression or death occurred in 670 women – 335 in each trial arm.
The rate of DFS 10 years after randomization was 73.6% in the 2-year additional-therapy group and 73.9% in the 5-year group. The hazard ratio for disease recurrence or death was 0.99 and was not significant. After adjustment for potential confounding factors, the HR remained essentially unchanged (HR, 1.0).
Overall survival at 8 years, a secondary endpoint, was virtually identical between the groups, at 87.5% in the 2-year group and 87.3% in the 5-year group. The HR for death from any cause was 1.02 and was not significant.
The HR for contralateral breast cancer was 1.15, and the HR for a second primary cancer was 1.06; neither was statistically significant.
Although the use of bone-targeted medication was similar between the groups, among patients in the 2-year group, the incidence of clinical bone fractures 5 years after randomization was lower, at 4.7% versus 6.3%, which translates to an HR for fracture with 5 additional years of AI therapy of 1.35 (95% confidence interval, 1.00-1.84).
Adverse events with anastrozole were consistent with its known toxicity profile. At least one serious adverse event occurred in 26.5% of patients in the 2-year group and in 40.2% in the 5-year group. Investigator-assessed serious adverse events that were judged to be related to anastrozole occurred in 2.3% and 4.0% of patients, respectively.
Osteoarthritis, the most frequently reported adverse event, was documented in 1.7% of patients in the 2-year group and in 4.3% in the 5-year group.
AI duration still unclear
“We did not investigate the value of extending adjuvant endocrine therapy per se, since the benefit of extending aromatase inhibitors after 5 years of adjuvant tamoxifen has been well established. In contrast, the most effective duration of adjuvant aromatase inhibitor therapy remains unclear in randomized trials,” Dr. Gnant and colleagues commented.
In her editorial, Dr. Goodwin summarized potential approaches for improving late outcomes for patients with hormone receptor–positive breast cancers, including the use of biomarkers to detect minimal residual disease and therapies to treat it.
She noted that the detection of circulating tumor cells in patients with HR-positive breast cancer 5 years after diagnosis is associated with a 13-fold increase in risk for recurrence and a median time to clinical recurrence of 2.8 years.
“This interval may be sufficiently long that therapeutic intervention can prevent the development of incurable clinical metastases. Continued improvement in these assays and the development of new therapies that target the unique biologic features of dormant cells will no doubt be required for a major reduction in late recurrence risk,” she wrote.
The study was supported by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group. Dr. Gnant has received lecture fees from AstraZeneca and others. Dr. Goodwin has received institutional research funding from the Breast Cancer Research Foundation and EPIC Sciences.
A version of this article first appeared on Medscape.com.
One in three cancer articles on social media has wrong info
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
FDA approves neoadjuvant pembro for triple-negative breast cancer
This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.
This is the 30th indication for pembrolizumab in the United States.
The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.
“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”
In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.
The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.
Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).
Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.
These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”
Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.
Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.
A version of this article first appeared on Medscape.com.
This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.
This is the 30th indication for pembrolizumab in the United States.
The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.
“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”
In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.
The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.
Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).
Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.
These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”
Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.
Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.
A version of this article first appeared on Medscape.com.
This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.
This is the 30th indication for pembrolizumab in the United States.
The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.
“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”
In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.
The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.
Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).
Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.
These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”
Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.
Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.
A version of this article first appeared on Medscape.com.
Clinical Edge Journal Scan Commentary: Breast Cancer August 2021
Program death-ligand 1 (PD-L1) inhibition suppresses tumor activity via modulation of immune and tumor cell interaction. TNBC is characterized by higher PD-L1 expression and increased immune infiltration, compared to other subtypes. In the randomized, phase 3 IMpassion130 trial, among 902 patients who were treatment naïve in the metastatic TNBC setting, an exploratory analysis in the PD-L1-positive population demonstrated a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel (25.4 vs 17.9 months; HR 0.67) (Emens et al). Additionally, the phase 3 KEYNOTE-355 trial demonstrated PFS benefit among patients with mTNBC with combined positive score (CPS) ≥10 with pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) versus placebo + chemotherapy (mPFS 9.7 vs 5.6 months; HR 0.65, 95% CI 0.49-0.86). These results are in contrast to the phase 3 IMpassion131 trial which found no statistically significant difference in PFS or OS among 651 patients with mTNBC randomized to atezolizumab + paclitaxel vs placebo + paclitaxel (PD-L1-positive population: PFS 6.0 vs 5.7 months, HR 0.82, 95% CI 0.60-1.12; OS 22.1 vs 28.3 months, HR 1.11, 95% CI 0.76-1.62) (Miles et al). The reasons underlying these differences remain unclear and warrant further investigation. Some thoughts raised include lack of information on BRCA status (which may serve as prognostic factor) in IMpassion131, concomitant use of steroids with paclitaxel, and allowance of sufficient long-term follow-up for generation of events. Regardless, these studies suggest chemotherapy backbone is relevant and the regimens utilized in IMpassion130 and KEYNOTE-355 have gained FDA approval in the first-line mTNBC setting.
The phase 3 CLEOPATRA trial has established the regimen of docetaxel + trastuzumab + pertuzumab as standard of care in the first-line setting for metastatic HER2-positive breast cancer with an OS benefit of 16 months compared to docetaxel + trastuzumab + placebo (57.1 vs 40.8 months; HR 0.69, 95% CI 0.58-0.82) with over 8 years of follow-up. PERUSE was a single-arm phase 3b study that investigated the safety and efficacy of trastuzumab + pertuzumab combined with various taxanes (docetaxel, paclitaxel or nab-paclitaxel) among 1426 patients with HER2+ mBC (Miles et al). In the overall population at follow-up of 5.7 years, median PFS and OS were 20.7 and 65.3 months, respectively, and were similar regardless of taxane backbone. Docetaxel was associated with higher incidences of neutropenia and febrile neutropenia. These results support consideration of an alternative taxane combined with trastuzumab + pertuzumab in this setting (for example paclitaxel) in patients who may not be ideal candidates for docetaxel.
In the second-line treatment setting for HER2+ mBC with prior exposure to trastuzumab and taxane, the phase 3 EMILIA study showed improvement in OS with T-DM1 vs capecitabine + lapatinib (mOS 29.9 vs 25.9 months, HR 0.75, 95% CI 0.64-0.88). Ethier et al explored real-world application and outcomes associated with pertuzumab and T-DM1 in the first- and second-line settings respectively, in a population-based, retrospective cohort study in Ontario, Canada. In the pertuzumab cohort, median OS and time on treatment were 43 and 4 months, respectively. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively. Additionally, patients in the T-DM1 cohort who were pertuzumab-naïve appeared to do better, potentially suggesting less responsiveness to subsequent HER2-targeted treatment in the real world setting among those who received prior pertuzumab. Findings from this population study demonstrate inferior outcomes when compared to the pivotal CLEOPATRA and EMILIA trials, and highlight a gap between clinical trial and real-world observations (described by authors as efficacy-effectiveness gap). Potential etiologies for these differences include patient factors, prior therapies and delivery of care models, and convey the importance of recognizing this gap exists and optimizing any modifiable factors as trial data and novel therapies are applied to routine clinical practice.
References:
Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70.
Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.
Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.
Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742.
Program death-ligand 1 (PD-L1) inhibition suppresses tumor activity via modulation of immune and tumor cell interaction. TNBC is characterized by higher PD-L1 expression and increased immune infiltration, compared to other subtypes. In the randomized, phase 3 IMpassion130 trial, among 902 patients who were treatment naïve in the metastatic TNBC setting, an exploratory analysis in the PD-L1-positive population demonstrated a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel (25.4 vs 17.9 months; HR 0.67) (Emens et al). Additionally, the phase 3 KEYNOTE-355 trial demonstrated PFS benefit among patients with mTNBC with combined positive score (CPS) ≥10 with pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) versus placebo + chemotherapy (mPFS 9.7 vs 5.6 months; HR 0.65, 95% CI 0.49-0.86). These results are in contrast to the phase 3 IMpassion131 trial which found no statistically significant difference in PFS or OS among 651 patients with mTNBC randomized to atezolizumab + paclitaxel vs placebo + paclitaxel (PD-L1-positive population: PFS 6.0 vs 5.7 months, HR 0.82, 95% CI 0.60-1.12; OS 22.1 vs 28.3 months, HR 1.11, 95% CI 0.76-1.62) (Miles et al). The reasons underlying these differences remain unclear and warrant further investigation. Some thoughts raised include lack of information on BRCA status (which may serve as prognostic factor) in IMpassion131, concomitant use of steroids with paclitaxel, and allowance of sufficient long-term follow-up for generation of events. Regardless, these studies suggest chemotherapy backbone is relevant and the regimens utilized in IMpassion130 and KEYNOTE-355 have gained FDA approval in the first-line mTNBC setting.
The phase 3 CLEOPATRA trial has established the regimen of docetaxel + trastuzumab + pertuzumab as standard of care in the first-line setting for metastatic HER2-positive breast cancer with an OS benefit of 16 months compared to docetaxel + trastuzumab + placebo (57.1 vs 40.8 months; HR 0.69, 95% CI 0.58-0.82) with over 8 years of follow-up. PERUSE was a single-arm phase 3b study that investigated the safety and efficacy of trastuzumab + pertuzumab combined with various taxanes (docetaxel, paclitaxel or nab-paclitaxel) among 1426 patients with HER2+ mBC (Miles et al). In the overall population at follow-up of 5.7 years, median PFS and OS were 20.7 and 65.3 months, respectively, and were similar regardless of taxane backbone. Docetaxel was associated with higher incidences of neutropenia and febrile neutropenia. These results support consideration of an alternative taxane combined with trastuzumab + pertuzumab in this setting (for example paclitaxel) in patients who may not be ideal candidates for docetaxel.
In the second-line treatment setting for HER2+ mBC with prior exposure to trastuzumab and taxane, the phase 3 EMILIA study showed improvement in OS with T-DM1 vs capecitabine + lapatinib (mOS 29.9 vs 25.9 months, HR 0.75, 95% CI 0.64-0.88). Ethier et al explored real-world application and outcomes associated with pertuzumab and T-DM1 in the first- and second-line settings respectively, in a population-based, retrospective cohort study in Ontario, Canada. In the pertuzumab cohort, median OS and time on treatment were 43 and 4 months, respectively. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively. Additionally, patients in the T-DM1 cohort who were pertuzumab-naïve appeared to do better, potentially suggesting less responsiveness to subsequent HER2-targeted treatment in the real world setting among those who received prior pertuzumab. Findings from this population study demonstrate inferior outcomes when compared to the pivotal CLEOPATRA and EMILIA trials, and highlight a gap between clinical trial and real-world observations (described by authors as efficacy-effectiveness gap). Potential etiologies for these differences include patient factors, prior therapies and delivery of care models, and convey the importance of recognizing this gap exists and optimizing any modifiable factors as trial data and novel therapies are applied to routine clinical practice.
References:
Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70.
Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.
Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.
Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742.
Program death-ligand 1 (PD-L1) inhibition suppresses tumor activity via modulation of immune and tumor cell interaction. TNBC is characterized by higher PD-L1 expression and increased immune infiltration, compared to other subtypes. In the randomized, phase 3 IMpassion130 trial, among 902 patients who were treatment naïve in the metastatic TNBC setting, an exploratory analysis in the PD-L1-positive population demonstrated a clinically meaningful OS benefit with atezolizumab + nab-paclitaxel compared to placebo + nab-paclitaxel (25.4 vs 17.9 months; HR 0.67) (Emens et al). Additionally, the phase 3 KEYNOTE-355 trial demonstrated PFS benefit among patients with mTNBC with combined positive score (CPS) ≥10 with pembrolizumab + chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) versus placebo + chemotherapy (mPFS 9.7 vs 5.6 months; HR 0.65, 95% CI 0.49-0.86). These results are in contrast to the phase 3 IMpassion131 trial which found no statistically significant difference in PFS or OS among 651 patients with mTNBC randomized to atezolizumab + paclitaxel vs placebo + paclitaxel (PD-L1-positive population: PFS 6.0 vs 5.7 months, HR 0.82, 95% CI 0.60-1.12; OS 22.1 vs 28.3 months, HR 1.11, 95% CI 0.76-1.62) (Miles et al). The reasons underlying these differences remain unclear and warrant further investigation. Some thoughts raised include lack of information on BRCA status (which may serve as prognostic factor) in IMpassion131, concomitant use of steroids with paclitaxel, and allowance of sufficient long-term follow-up for generation of events. Regardless, these studies suggest chemotherapy backbone is relevant and the regimens utilized in IMpassion130 and KEYNOTE-355 have gained FDA approval in the first-line mTNBC setting.
The phase 3 CLEOPATRA trial has established the regimen of docetaxel + trastuzumab + pertuzumab as standard of care in the first-line setting for metastatic HER2-positive breast cancer with an OS benefit of 16 months compared to docetaxel + trastuzumab + placebo (57.1 vs 40.8 months; HR 0.69, 95% CI 0.58-0.82) with over 8 years of follow-up. PERUSE was a single-arm phase 3b study that investigated the safety and efficacy of trastuzumab + pertuzumab combined with various taxanes (docetaxel, paclitaxel or nab-paclitaxel) among 1426 patients with HER2+ mBC (Miles et al). In the overall population at follow-up of 5.7 years, median PFS and OS were 20.7 and 65.3 months, respectively, and were similar regardless of taxane backbone. Docetaxel was associated with higher incidences of neutropenia and febrile neutropenia. These results support consideration of an alternative taxane combined with trastuzumab + pertuzumab in this setting (for example paclitaxel) in patients who may not be ideal candidates for docetaxel.
In the second-line treatment setting for HER2+ mBC with prior exposure to trastuzumab and taxane, the phase 3 EMILIA study showed improvement in OS with T-DM1 vs capecitabine + lapatinib (mOS 29.9 vs 25.9 months, HR 0.75, 95% CI 0.64-0.88). Ethier et al explored real-world application and outcomes associated with pertuzumab and T-DM1 in the first- and second-line settings respectively, in a population-based, retrospective cohort study in Ontario, Canada. In the pertuzumab cohort, median OS and time on treatment were 43 and 4 months, respectively. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively. Additionally, patients in the T-DM1 cohort who were pertuzumab-naïve appeared to do better, potentially suggesting less responsiveness to subsequent HER2-targeted treatment in the real world setting among those who received prior pertuzumab. Findings from this population study demonstrate inferior outcomes when compared to the pivotal CLEOPATRA and EMILIA trials, and highlight a gap between clinical trial and real-world observations (described by authors as efficacy-effectiveness gap). Potential etiologies for these differences include patient factors, prior therapies and delivery of care models, and convey the importance of recognizing this gap exists and optimizing any modifiable factors as trial data and novel therapies are applied to routine clinical practice.
References:
Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70.
Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.
Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.
Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742.
Breast reconstruction: Chemotherapy does not increase complications and patient-reported outcomes
Key clinical point: Chemotherapy is not associated with postmastectomy breast reconstruction surgical complications or with most surgery-related patient-reported outcomes.
Major finding: Compared with no chemotherapy, no difference was observed in the risk for any/major complication with either neoadjuvant (P = .68 and .46, respectively) or adjuvant (P = .15 and .053, respectively) chemotherapy in patients who received implant-based procedures. In patients who received autologous reconstruction, the risk for 2-year postoperative any/major complication was similar with neoadjuvant (P = .25 and .11, respectively) and adjuvant (P = .44 and .40, respectively) chemotherapy vs no chemotherapy. There were no differences across the chemotherapy groups for most BREAST-Q subscales.
Study details: A multicenter cohort study of 1,881 women who underwent postmastectomy breast reconstruction and were followed up for 2 years.
Disclosures: This study was supported by the National Cancer Institute. The authors did not report any conflicts of interest.
Source: Hart SE et al. JAMA Surg. 2021 Jun 23. doi: 10.1001/jamasurg.2021.2239.
Key clinical point: Chemotherapy is not associated with postmastectomy breast reconstruction surgical complications or with most surgery-related patient-reported outcomes.
Major finding: Compared with no chemotherapy, no difference was observed in the risk for any/major complication with either neoadjuvant (P = .68 and .46, respectively) or adjuvant (P = .15 and .053, respectively) chemotherapy in patients who received implant-based procedures. In patients who received autologous reconstruction, the risk for 2-year postoperative any/major complication was similar with neoadjuvant (P = .25 and .11, respectively) and adjuvant (P = .44 and .40, respectively) chemotherapy vs no chemotherapy. There were no differences across the chemotherapy groups for most BREAST-Q subscales.
Study details: A multicenter cohort study of 1,881 women who underwent postmastectomy breast reconstruction and were followed up for 2 years.
Disclosures: This study was supported by the National Cancer Institute. The authors did not report any conflicts of interest.
Source: Hart SE et al. JAMA Surg. 2021 Jun 23. doi: 10.1001/jamasurg.2021.2239.
Key clinical point: Chemotherapy is not associated with postmastectomy breast reconstruction surgical complications or with most surgery-related patient-reported outcomes.
Major finding: Compared with no chemotherapy, no difference was observed in the risk for any/major complication with either neoadjuvant (P = .68 and .46, respectively) or adjuvant (P = .15 and .053, respectively) chemotherapy in patients who received implant-based procedures. In patients who received autologous reconstruction, the risk for 2-year postoperative any/major complication was similar with neoadjuvant (P = .25 and .11, respectively) and adjuvant (P = .44 and .40, respectively) chemotherapy vs no chemotherapy. There were no differences across the chemotherapy groups for most BREAST-Q subscales.
Study details: A multicenter cohort study of 1,881 women who underwent postmastectomy breast reconstruction and were followed up for 2 years.
Disclosures: This study was supported by the National Cancer Institute. The authors did not report any conflicts of interest.
Source: Hart SE et al. JAMA Surg. 2021 Jun 23. doi: 10.1001/jamasurg.2021.2239.
HER2-positive breast cancer: Novel targeted therapies fall short in real-world setting
Key clinical point: In the real-world setting, the overall survival (OS) with pertuzumab and trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor hormone receptor 2 (HER2)-positive metastatic breast cancer is inferior to results from pivotal clinical trials.
Major finding: The OS with pertuzumab and T-DM1 was shorter than that reported in the pivotal clinical trials. In the pertuzumab cohort, OS was 43 months and time on treatment was 14 months. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively.
Study details: A population-based retrospective cohort study of patients with ERBB2-positive metastatic breast cancer treated with first-line pertuzumab (n=795) or second-line T-DM1 (n=506).
Disclosures: This study was supported by the Canadian Institutes of Health Research. The authors received personal fees from various sources outside this work. Dr. CM Booth was supported as a Canada Research Chair in Population Cancer Care.
Source: Ethier JL et al. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2140.
Key clinical point: In the real-world setting, the overall survival (OS) with pertuzumab and trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor hormone receptor 2 (HER2)-positive metastatic breast cancer is inferior to results from pivotal clinical trials.
Major finding: The OS with pertuzumab and T-DM1 was shorter than that reported in the pivotal clinical trials. In the pertuzumab cohort, OS was 43 months and time on treatment was 14 months. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively.
Study details: A population-based retrospective cohort study of patients with ERBB2-positive metastatic breast cancer treated with first-line pertuzumab (n=795) or second-line T-DM1 (n=506).
Disclosures: This study was supported by the Canadian Institutes of Health Research. The authors received personal fees from various sources outside this work. Dr. CM Booth was supported as a Canada Research Chair in Population Cancer Care.
Source: Ethier JL et al. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2140.
Key clinical point: In the real-world setting, the overall survival (OS) with pertuzumab and trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor hormone receptor 2 (HER2)-positive metastatic breast cancer is inferior to results from pivotal clinical trials.
Major finding: The OS with pertuzumab and T-DM1 was shorter than that reported in the pivotal clinical trials. In the pertuzumab cohort, OS was 43 months and time on treatment was 14 months. In the T-DM1 cohort, median OS and time on treatment were 15 months and 4 months, respectively.
Study details: A population-based retrospective cohort study of patients with ERBB2-positive metastatic breast cancer treated with first-line pertuzumab (n=795) or second-line T-DM1 (n=506).
Disclosures: This study was supported by the Canadian Institutes of Health Research. The authors received personal fees from various sources outside this work. Dr. CM Booth was supported as a Canada Research Chair in Population Cancer Care.
Source: Ethier JL et al. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2140.
Oligometastatic breast cancer: SABR extends long-term survival
Key clinical point: Stereotactic ablative body radiotherapy (SABR) leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.
Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival (OS) was 86 months, and progression-free survival (PFS) was 33 months. The receipt of SABR within 5 years of diagnosis (P = .004) and presence of triple-negative breast cancer (TNBC; P = .013) were associated with worse OS. Advanced T stage (P = .062) and TNBC (P = .013) were associated with worse PFS.
Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.
Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.
Source: Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068.
Key clinical point: Stereotactic ablative body radiotherapy (SABR) leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.
Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival (OS) was 86 months, and progression-free survival (PFS) was 33 months. The receipt of SABR within 5 years of diagnosis (P = .004) and presence of triple-negative breast cancer (TNBC; P = .013) were associated with worse OS. Advanced T stage (P = .062) and TNBC (P = .013) were associated with worse PFS.
Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.
Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.
Source: Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068.
Key clinical point: Stereotactic ablative body radiotherapy (SABR) leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.
Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival (OS) was 86 months, and progression-free survival (PFS) was 33 months. The receipt of SABR within 5 years of diagnosis (P = .004) and presence of triple-negative breast cancer (TNBC; P = .013) were associated with worse OS. Advanced T stage (P = .062) and TNBC (P = .013) were associated with worse PFS.
Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.
Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.
Source: Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068.