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Immediate breast reconstruction after chemotherapy doesn’t hurt survival
Key clinical point: Outcomes including recurrence, disease-free survival, and overall survival were similar for breast cancer patients who underwent immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) following neoadjuvant chemotherapy.
Major finding: Breast cancer patients who underwent IBR with NSM/SSM as surgical treatment showed similar rates of overall survival at 5 years compared to those who underwent conventional mastectomy (92.0% vs. 89.3%).
Study details: The data come from a retrospective, case-control study of 1,266 breast cancer patients who underwent neoadjuvant chemotherapy followed by immediate breast reconstruction or conventional mastectomy at a single center between January 1, 2010, and November 30, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Wu Z-Y et al. JAMA Surg. 2020 Oct 14. doi: 10.1001/jamasurg.2020.4132.
Key clinical point: Outcomes including recurrence, disease-free survival, and overall survival were similar for breast cancer patients who underwent immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) following neoadjuvant chemotherapy.
Major finding: Breast cancer patients who underwent IBR with NSM/SSM as surgical treatment showed similar rates of overall survival at 5 years compared to those who underwent conventional mastectomy (92.0% vs. 89.3%).
Study details: The data come from a retrospective, case-control study of 1,266 breast cancer patients who underwent neoadjuvant chemotherapy followed by immediate breast reconstruction or conventional mastectomy at a single center between January 1, 2010, and November 30, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Wu Z-Y et al. JAMA Surg. 2020 Oct 14. doi: 10.1001/jamasurg.2020.4132.
Key clinical point: Outcomes including recurrence, disease-free survival, and overall survival were similar for breast cancer patients who underwent immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) following neoadjuvant chemotherapy.
Major finding: Breast cancer patients who underwent IBR with NSM/SSM as surgical treatment showed similar rates of overall survival at 5 years compared to those who underwent conventional mastectomy (92.0% vs. 89.3%).
Study details: The data come from a retrospective, case-control study of 1,266 breast cancer patients who underwent neoadjuvant chemotherapy followed by immediate breast reconstruction or conventional mastectomy at a single center between January 1, 2010, and November 30, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Wu Z-Y et al. JAMA Surg. 2020 Oct 14. doi: 10.1001/jamasurg.2020.4132.
Black women show higher rates of three breast cancer subtypes
Key clinical point: Breast cancer subtypes may be associated with race and ethnicity; certain subtypes were significantly more common in Black women and infiltrating duct carcinoma compared to White women, but lobular carcinoma, and tubular adenocarcinoma were less common in Hispanic women compared to nonHispanic White women.
Major finding: The incidence of HR-negative and ERBB2-positive; HR-positive and ERBB2-positive; and triple negative breast cancer was significantly higher among Black women compared to nonHispanic White women, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (incidence rate ratios of 1.12, 1.46, 2.07, and 0.86, respectively).
Study details: The data come from a population-based cohort study of 239,211 women with breast cancer diagnosed between January 1, 2010, and December 31, 2015.
Disclosures: The study was supported by grants to the researchers from several organizations including the Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Special Research Fund for Central Universities, Peking Union Medical College, the Beijing Hope Run Special Fund of Cancer Foundation of China, and the PhD Innovation Fund of Cancer Hospital, Chinese Academy of Medical Sciences. The researchers had no financial conflicts to disclose.
Citation: Kong X et al. JAMA Netw Open. 2020 Oct 19. doi:10.1001/jamanetworkopen.2020.20303.
Key clinical point: Breast cancer subtypes may be associated with race and ethnicity; certain subtypes were significantly more common in Black women and infiltrating duct carcinoma compared to White women, but lobular carcinoma, and tubular adenocarcinoma were less common in Hispanic women compared to nonHispanic White women.
Major finding: The incidence of HR-negative and ERBB2-positive; HR-positive and ERBB2-positive; and triple negative breast cancer was significantly higher among Black women compared to nonHispanic White women, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (incidence rate ratios of 1.12, 1.46, 2.07, and 0.86, respectively).
Study details: The data come from a population-based cohort study of 239,211 women with breast cancer diagnosed between January 1, 2010, and December 31, 2015.
Disclosures: The study was supported by grants to the researchers from several organizations including the Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Special Research Fund for Central Universities, Peking Union Medical College, the Beijing Hope Run Special Fund of Cancer Foundation of China, and the PhD Innovation Fund of Cancer Hospital, Chinese Academy of Medical Sciences. The researchers had no financial conflicts to disclose.
Citation: Kong X et al. JAMA Netw Open. 2020 Oct 19. doi:10.1001/jamanetworkopen.2020.20303.
Key clinical point: Breast cancer subtypes may be associated with race and ethnicity; certain subtypes were significantly more common in Black women and infiltrating duct carcinoma compared to White women, but lobular carcinoma, and tubular adenocarcinoma were less common in Hispanic women compared to nonHispanic White women.
Major finding: The incidence of HR-negative and ERBB2-positive; HR-positive and ERBB2-positive; and triple negative breast cancer was significantly higher among Black women compared to nonHispanic White women, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (incidence rate ratios of 1.12, 1.46, 2.07, and 0.86, respectively).
Study details: The data come from a population-based cohort study of 239,211 women with breast cancer diagnosed between January 1, 2010, and December 31, 2015.
Disclosures: The study was supported by grants to the researchers from several organizations including the Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Special Research Fund for Central Universities, Peking Union Medical College, the Beijing Hope Run Special Fund of Cancer Foundation of China, and the PhD Innovation Fund of Cancer Hospital, Chinese Academy of Medical Sciences. The researchers had no financial conflicts to disclose.
Citation: Kong X et al. JAMA Netw Open. 2020 Oct 19. doi:10.1001/jamanetworkopen.2020.20303.
Pregnancy outcomes ‘favorable’ after BRCA breast cancer treatment
said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.
It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.
The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.
The review was published in September in the Journal of Clinical Oncology.
The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.
More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.
Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.
The miscarriage rate was 10.3%, lower than expected in the general population.
Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.
There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.
Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).
Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).
The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).
The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
A version of this article originally appeared on Medscape.com.
said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.
It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.
The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.
The review was published in September in the Journal of Clinical Oncology.
The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.
More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.
Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.
The miscarriage rate was 10.3%, lower than expected in the general population.
Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.
There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.
Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).
Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).
The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).
The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
A version of this article originally appeared on Medscape.com.
said researchers reporting a review of more than 1,000 young women with breast cancer, mostly in Europe but also Israel and North and South America.
It’s been known that pregnancy after breast cancer treatment, even for hormone receptor–positive disease, is safe overall, the team commented. However, there have been concerns about women who have BRCA mutations because of a lack of data.
The new findings “provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility” and are of “paramount importance for health care providers involved in counseling young patients,” said the researchers, led by Matteo Lambertini, MD, PhD, a medical oncologist at the University of Genoa, Italy.
The review was published in September in the Journal of Clinical Oncology.
The team reviewed reproductive outcomes among 1,252 women who were no older than 40 years when diagnosed with stage I-III BRCA-mutated invasive breast cancer between January 2000 and December 2012.
More than half (65%; n = 811) had BRCA1 mutations, 430 women (34%) had BRCA2 mutations, and 11 women had both.
Overall, 195 women became pregnant, at a median of 4.5 years after the breast cancer diagnosis and at a median age of 36 years.
The miscarriage rate was 10.3%, lower than expected in the general population.
Among the 150 patients who gave birth to 170 infants, delivery complications occurred in 13 of the 112 pregnancies with available data (11.6%), and congenital anomalies were seen in just 2 pregnancies (1.8%). This is a lower rate of anomalies than expected in the general population, the team noted. The rate of preterm delivery was 9.2%, similar to the general population.
There was no difference between the women who became pregnant and those who did not in either disease-free survival (adjusted hazard ratio, 0.87; P = .41) or overall survival (aHR, 0.88; P = .66), over a median follow-up of 8.3 years from diagnosis. In addition to BRCA mutations, the analysis adjusted for age at diagnosis, tumor size, nodal status, hormone receptor status, type of endocrine therapy, and breast surgery.
Over 80% of the subjects had ductal carcinoma, and over 90% of women were HER2-negative. More women in the pregnancy cohort had tumor diameters of 2 cm or less (47.2% vs. 40.9%) and a higher percentage had breast conserving surgery (59% vs. 45.9%).
Chemotherapy was administered to 95.3% of the subjects, most commonly anthracycline and taxane based, and more than 90% received endocrine therapy, most often tamoxifen alone among women who did not become pregnant and tamoxifen plus a luteinizing hormone-releasing hormone agonist among those who did. Endocrine therapy was shorter among women who became pregnant (median, 50 vs. 60 months; P < .001).
The findings held when 176 pregnant cases were matched to 528 nonpregnant controls for year of diagnosis, nodal status, hormone receptor status, and type of BRCA mutation. However, disease-free survival was improved among pregnant women (HR, 0.71; P = .045) who were younger at diagnosis, with median ages of 31 years vs. 36 years (P < .001).
The study was funded by the Italian Association for Cancer Research, among others. Dr. Lambertini reports acting as a consultant for Roche and Novartis and as a speaker for Theramex, Takeda, Roche, Eli Lilly, Novartis. Several coauthors also report relationships with pharmaceutical companies, as detailed in the original article.
A version of this article originally appeared on Medscape.com.
Using telehealth to deliver palliative care to cancer patients
Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.
Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.
Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.
Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.
For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.
For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.
These issues make it attractive to consider whether telehealth could be used for palliative care services.
Scarcity of palliative care specialists
In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.
In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.
For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.
Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
Special considerations regarding telehealth for palliative care
As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.
Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.
Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.
Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
REACH PC study demonstrates feasibility of telehealth model
Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.
The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.
Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.
Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).
Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.
Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).
When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.
When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.
The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
‘Webside’ manner
Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.
For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
Is telehealth the future of palliative care?
I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.
To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.
In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.
For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.
Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”
The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.
Dr. Temel disclosed institutional research funding from Pfizer.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.
Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.
Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.
Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.
For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.
For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.
These issues make it attractive to consider whether telehealth could be used for palliative care services.
Scarcity of palliative care specialists
In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.
In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.
For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.
Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
Special considerations regarding telehealth for palliative care
As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.
Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.
Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.
Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
REACH PC study demonstrates feasibility of telehealth model
Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.
The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.
Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.
Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).
Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.
Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).
When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.
When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.
The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
‘Webside’ manner
Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.
For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
Is telehealth the future of palliative care?
I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.
To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.
In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.
For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.
Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”
The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.
Dr. Temel disclosed institutional research funding from Pfizer.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Traditional delivery of palliative care to outpatients with cancer is associated with many challenges.
Telehealth can eliminate some of these challenges but comes with issues of its own, according to results of the REACH PC trial.
Jennifer S. Temel, MD, of Massachusetts General Hospital in Boston, discussed the use of telemedicine in palliative care, including results from REACH PC, during an educational session at the ASCO Virtual Quality Care Symposium 2020.
Dr. Temel noted that, for cancer patients, an in-person visit with a palliative care specialist can cost time, induce fatigue, and increase financial burden from transportation and parking expenses.
For caregivers and family, an in-person visit may necessitate absence from family and/or work, require complex scheduling to coordinate with other office visits, and result in additional transportation and/or parking expenses.
For health care systems, to have a dedicated palliative care clinic requires precious space and financial expenditures for office personnel and other resources.
These issues make it attractive to consider whether telehealth could be used for palliative care services.
Scarcity of palliative care specialists
In the United States, there is roughly 1 palliative care physician for every 20,000 older adults with a life-limiting illness, according to research published in Annual Review of Public Health in 2014.
In its 2019 state-by-state report card, the Center to Advance Palliative Care noted that only 72% of U.S. hospitals with 50 or more beds have a palliative care team.
For patients with serious illnesses and those who are socioeconomically or geographically disadvantaged, palliative care is often inaccessible.
Inefficiencies in the current system are an additional impediment. Palliative care specialists frequently see patients during a portion of the patient’s routine visit to subspecialty or primary care clinics. This limits the palliative care specialist’s ability to perform comprehensive assessments and provide patient-centered care efficiently.
Special considerations regarding telehealth for palliative care
As a specialty, palliative care involves interactions that could make the use of telehealth problematic. For example, conveyance of interest, warmth, and touch are challenging or impossible in a video format.
Palliative care specialists engage with patients regarding relatively serious topics such as prognosis and end-of-life preferences. There is uncertainty about how those discussions would be received by patients and their caregivers via video.
Furthermore, there are logistical impediments such as prescribing opioids with video or across state lines.
Despite these concerns, the ENABLE study showed that supplementing usual oncology care with weekly (transitioning to monthly) telephone-based educational palliative care produced higher quality of life and mood than did usual oncology care alone. These results were published in JAMA in 2009.
REACH PC study demonstrates feasibility of telehealth model
Dr. Temel described the ongoing REACH PC trial in which palliative care is delivered via video visits and compared with in-person palliative care for patients with advanced non–small cell lung cancer.
The primary aim of REACH PC is to determine whether telehealth palliative care is equivalent to traditional palliative care in improving quality of life as a supplement to routine oncology care.
Currently, REACH PC has enrolled 581 patients at its 20 sites, spanning a geographically diverse area. Just over half of patients approached about REACH PC agreed to enroll in it. Ultimately, 1,250 enrollees are sought.
Among patients who declined to participate, 7.6% indicated “discomfort with technology” as the reason. Most refusals were due to lack of interest in research (35.1%) and/or palliative care (22.9%).
Older adults were prominent among enrollees. More than 60% were older than 60 years of age, and more than one-third were older than 70 years.
Among patients who began the trial, there were slightly more withdrawals in the telehealth participants, in comparison with in-person participants (13.6% versus 9.1%).
When palliative care clinicians were queried about video visits, 64.3% said there were no challenges. This is comparable to the 65.5% of clinicians who had no challenges with in-person visits.
When problems occurred with video visits, they were most frequently technical (19.1%). Only 1.4% of clinicians reported difficulty addressing topics that felt uncomfortable over video, and 1.5% reported difficulty establishing rapport.
The success rates of video and in-person visits were similar. About 80% of visits accomplished planned goals.
‘Webside’ manner
Strategies such as reflective listening and summarizing what patients say (to verify an accurate understanding of the patient’s perspective) are key to successful palliative care visits, regardless of the setting.
For telehealth visits, Dr. Temel described techniques she defined as “webside manner,” to compensate for the inability of the clinician to touch a patient. These techniques include leaning in toward the camera, nodding, and pausing to be certain the patient has finished speaking before the clinician speaks again.
Is telehealth the future of palliative care?
I include myself among those oncologists who have voiced concern about moving from face-to-face to remote visits for complicated consultations such as those required for palliative care. Nonetheless, from the preliminary results of the REACH PC trial, it appears that telehealth could be a valuable tool.
To minimize differences between in-person and remote delivery of palliative care, practical strategies for ensuring rapport and facilitating a trusting relationship should be defined further and disseminated.
In addition, we need to be vigilant for widening inequities of care from rapid movement to the use of technology (i.e., an equity gap). In their telehealth experience during the COVID-19 pandemic, investigators at Houston Methodist Cancer Center found that patients declining virtual visits tended to be older, lower-income, and less likely to have commercial insurance. These results were recently published in JCO Oncology Practice.
For the foregoing reasons, hybrid systems for palliative care services will probably always be needed.
Going forward, we should heed the advice of Alvin Toffler in his book Future Shock. Mr. Toffler said, “The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn.”
The traditional model for delivering palliative care will almost certainly need to be reimagined and relearned.
Dr. Temel disclosed institutional research funding from Pfizer.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM ASCO QUALITY CARE SYMPOSIUM 2020
Pembrolizumab approved for triple-negative breast cancer
The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) in combination with chemotherapy to treat locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1, as determined by a combined positive score of 10 or greater on an FDA-approved assay.
The FDA also approved a PD-L1 assay for selecting TNBC patients for pembrolizumab, the PD-L1 IHC 22C3 pharmDx.
Pembrolizumab is approved for numerous indications in the United States, but the new approval is its first breast cancer indication.
The accelerated approval for pembrolizumab in TNBC was based on progression-free survival (PFS) in the KEYNOTE-355 trial. The FDA noted that continued approval of pembrolizumab in TNBC “may be contingent upon verification and description of clinical benefit in the confirmatory trials.”
KEYNOTE-355 enrolled patients with locally recurrent unresectable or metastatic TNBC who had not received chemotherapy in the metastatic setting. Patients were randomized to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) plus placebo (n = 281) or chemotherapy plus pembrolizumab at 200 mg on day 1 every 3 weeks (n = 562).
Among PD-L1-positive patients (n = 323), the median PFS was 5.6 months in the placebo arm and 9.7 months in the pembrolizumab arm (hazard ratio, 0.65; P = .0012).
The recommended pembrolizumab dose in TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Pembrolizumab can cause immune-mediated adverse reactions that may be severe or fatal, according to Merck, the manufacturer of pembrolizumab. These adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplant.
“Based on the severity of the adverse reaction, [pembrolizumab] should be withheld or discontinued and corticosteroids administered if appropriate,” the company noted.
For more details on pembrolizumab, see the full prescribing information.
The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) in combination with chemotherapy to treat locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1, as determined by a combined positive score of 10 or greater on an FDA-approved assay.
The FDA also approved a PD-L1 assay for selecting TNBC patients for pembrolizumab, the PD-L1 IHC 22C3 pharmDx.
Pembrolizumab is approved for numerous indications in the United States, but the new approval is its first breast cancer indication.
The accelerated approval for pembrolizumab in TNBC was based on progression-free survival (PFS) in the KEYNOTE-355 trial. The FDA noted that continued approval of pembrolizumab in TNBC “may be contingent upon verification and description of clinical benefit in the confirmatory trials.”
KEYNOTE-355 enrolled patients with locally recurrent unresectable or metastatic TNBC who had not received chemotherapy in the metastatic setting. Patients were randomized to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) plus placebo (n = 281) or chemotherapy plus pembrolizumab at 200 mg on day 1 every 3 weeks (n = 562).
Among PD-L1-positive patients (n = 323), the median PFS was 5.6 months in the placebo arm and 9.7 months in the pembrolizumab arm (hazard ratio, 0.65; P = .0012).
The recommended pembrolizumab dose in TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Pembrolizumab can cause immune-mediated adverse reactions that may be severe or fatal, according to Merck, the manufacturer of pembrolizumab. These adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplant.
“Based on the severity of the adverse reaction, [pembrolizumab] should be withheld or discontinued and corticosteroids administered if appropriate,” the company noted.
For more details on pembrolizumab, see the full prescribing information.
The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) in combination with chemotherapy to treat locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1, as determined by a combined positive score of 10 or greater on an FDA-approved assay.
The FDA also approved a PD-L1 assay for selecting TNBC patients for pembrolizumab, the PD-L1 IHC 22C3 pharmDx.
Pembrolizumab is approved for numerous indications in the United States, but the new approval is its first breast cancer indication.
The accelerated approval for pembrolizumab in TNBC was based on progression-free survival (PFS) in the KEYNOTE-355 trial. The FDA noted that continued approval of pembrolizumab in TNBC “may be contingent upon verification and description of clinical benefit in the confirmatory trials.”
KEYNOTE-355 enrolled patients with locally recurrent unresectable or metastatic TNBC who had not received chemotherapy in the metastatic setting. Patients were randomized to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) plus placebo (n = 281) or chemotherapy plus pembrolizumab at 200 mg on day 1 every 3 weeks (n = 562).
Among PD-L1-positive patients (n = 323), the median PFS was 5.6 months in the placebo arm and 9.7 months in the pembrolizumab arm (hazard ratio, 0.65; P = .0012).
The recommended pembrolizumab dose in TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Pembrolizumab can cause immune-mediated adverse reactions that may be severe or fatal, according to Merck, the manufacturer of pembrolizumab. These adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplant.
“Based on the severity of the adverse reaction, [pembrolizumab] should be withheld or discontinued and corticosteroids administered if appropriate,” the company noted.
For more details on pembrolizumab, see the full prescribing information.
FROM THE FOOD AND DRUG ADMINISTRATION
Late-onset epilepsy tied to a threefold increased dementia risk
Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy.
“This is an exciting area, as we are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other cohort studies are finding similar results, including the Veterans’ Health Study and the Framingham Study,” she added.
The study was published online Oct. 23 in Neurology
Bidirectional relationship?
Previous research has established that dementia is a risk factor for epilepsy, but recent studies also suggest an increased risk of incident dementia among patients with adult-onset epilepsy. Several risk factors for late-onset epilepsy, including diabetes and hypertension, also are risk factors for dementia. However, the effect of late-onset epilepsy on dementia risk in patients with these comorbidities has not been clarified.
To investigate, the researchers examined data from the Atherosclerosis Risk in Communities (ARIC) study. Participants include Black and White men and women from four U.S. communities. Baseline visits in this longitudinal cohort study began between 1987 and 1989, and follow-up included seven additional visits and regular phone calls.
The investigators identified participants with late-onset epilepsy by searching for Medicare claims related to seizures or epilepsy filed between 1991 and 2015. Those with two or more such claims and age of onset of 67 years or greater were considered to have late-onset epilepsy. Participants with preexisting conditions such as brain tumors or multiple sclerosis were excluded.
ARIC participants who presented in person for visits 2, 4, 5, and 6 underwent cognitive testing with the Delayed Word Recall Test, the Digit Symbol Substitution Test, and the Word Fluency Test.
Testing at visits 5 and 6 also included other tests, such as the Mini-Mental State Examination, the Boston Naming test, and the Wechsler Memory Scale-III. Dr. Johnson and colleagues excluded data for visit 7 from the analysis because dementia adjudication was not yet complete.
The researchers identified participants with dementia using data from visits 5 and 6 and ascertained time of dementia onset through participant and informant interviews, phone calls, and hospital discharge data. Participants also were screened for mild cognitive impairment (MCI) at visits 5 and 6.
Data were analyzed using a Cox proportional hazards model and multinomial logistic regression. In subsequent analyses, researchers adjusted the data for age, sex, race, smoking status, alcohol use, hypertension, diabetes, body mass index (BMI), APOE4 status, and prevalent stroke.
The researchers found that of 9,033 study participants, 671 had late-onset epilepsy. The late-onset epilepsy group was older at baseline (56.5 vs. 55.1 years) and more likely to have hypertension (38.9% vs. 33.3%), diabetes (16.1% vs. 9.6%), and two alleles of APOE4 genotype (3.9% vs. 2.5%), compared with those without the disorder.
In all, 1,687 participants developed dementia during follow-up. The rate of incident dementia was 41.6% in participants with late-onset epilepsy and 16.8% in participants without late-onset epilepsy. The adjusted hazard ratio of subsequent dementia in participants with late-onset epilepsy versus those without the disorder was 3.05 (95% confidence interval, 2.65-3.51).
The median time to dementia ascertainment after late-onset epilepsy was 3.66 years.
Counterintuitive finding
The relationship between late-onset epilepsy and subsequent dementia was stronger in patients without stroke. The investigators offered a possible explanation for this counterintuitive finding. “We observed an interaction between [late-onset epilepsy] and stroke, with a lower (but still substantial) association between [late-onset epilepsy] and dementia in those with a history of stroke. This may be due to the known strong association between stroke and dementia, which may wash out the contributions of [late-onset epilepsy] to cognitive impairment,” the researchers wrote.
“There may also be under-capturing of dementia diagnoses among participants with stroke in the ascertainment from [Centers for Medicare & Medicaid Services] codes, as physicians may be reluctant to make a separate code for ‘dementia’ in those with cognitive impairment after stroke,” they added.
When the researchers restricted the analysis only to participants who attended visits 5 and 6 and had late-onset epilepsy ascertainment available, they found that the relative risk ratio for dementia at visit 6 was 2.90 (95% CI, 1.22-6.92; P = .009). The RRR for MCI was 0.97 (95% CI, 0.39-2.38; P = .803). The greater functional impairment in patients with late-onset epilepsy may explain the lack of a relationship between late-onset epilepsy and MCI.
“It will be important for neurologists to be aware of the possibility of cognitive impairment following late-onset epilepsy and to check in with patients and family members to see if there are concerns,” said Dr. Johnson.
“We should also be talking about the importance of lowering other risk factors for dementia by making sure cardiovascular risk factors are controlled and encouraging physical and cognitive activity,” she added.
The results require confirmation in a clinical population, the investigators noted. In addition, future research is necessary to clarify whether seizures directly increase the risk of dementia or whether shared neuropathology between epilepsy and dementia explains the risk.
“In the near future, I plan to enroll participants with late-onset epilepsy in an observational study to better understand factors that may contribute to cognitive change. Collaborations will be key as we seek to further understand what causes these changes and what could be done to prevent them,” Dr. Johnson added.
Strengths and weaknesses
In an accompanying editorial, W. Allen Hauser, MD, professor emeritus of neurology and epidemiology at Columbia University in New York, and colleagues noted that the findings support a bidirectional relationship between dementia and epilepsy, adding that accumulation of amyloid beta peptide is a plausible underlying pathophysiology that may explain this relationship.
Future research should clarify the effect of factors such as seizure type, seizure frequency, and age of onset on the risk of dementia among patients with epilepsy, the editorialists wrote. Such investigations could help elucidate the underlying mechanisms of these conditions and help to improve treatment, they added.
Commenting on the findings, Ilo Leppik, MD, professor of neurology and pharmacy at the University of Minnesota in Minneapolis described the research as “a very well-done study by qualified researchers in the field. … For the last century, medicine has unfortunately become compartmentalized by specialty and then subspecialty. The brain and disorders of the brain do not recognize these silos. … It is not a stretch of the known science to begin to understand that epilepsy and dementia have common anatomical and physiological underpinnings.”
The long period of prospectively gathering data and the measurement of cognitive function through various modalities are among the study’s great strengths, said Dr. Leppik. However, the study’s weakness is its reliance on Medicare claims data, which mainly would reflect convulsive seizures.
“What is missing is how many persons had subtle focal-unaware seizures that may not be identified unless a careful history is taken,” said Dr. Leppik. “Thus, this study likely underestimates the frequency of epilepsy.”
Neurologists who evaluate a person with early dementia should be on the lookout for a history of subtle seizures, said Dr. Leppik. Animal studies suggest treatment with levetiracetam or brivaracetam may slow the course of dementia, and a clinical study in participants with early dementia is underway.
“Treatment with an antiseizure drug may prove to be beneficial, especially if evidence for the presence of subtle epilepsy can be found,” Dr. Leppik added.
Greater collaboration between epileptologists and dementia specialists and larger studies of antiseizure drugs are necessary, he noted. “These studies can incorporate sophisticated structural and biochemical [analyses] to better identify the relationships between brain mechanisms that likely underlie both seizures and dementia. The ultimate promise is that early treatment of seizures may alter the course of dementia,” Dr. Leppik said.
The study by Dr. Johnson and colleagues was supported by a contract from the National Institute on Aging; ARIC from the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. The authors and Dr. Leppik have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy.
“This is an exciting area, as we are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other cohort studies are finding similar results, including the Veterans’ Health Study and the Framingham Study,” she added.
The study was published online Oct. 23 in Neurology
Bidirectional relationship?
Previous research has established that dementia is a risk factor for epilepsy, but recent studies also suggest an increased risk of incident dementia among patients with adult-onset epilepsy. Several risk factors for late-onset epilepsy, including diabetes and hypertension, also are risk factors for dementia. However, the effect of late-onset epilepsy on dementia risk in patients with these comorbidities has not been clarified.
To investigate, the researchers examined data from the Atherosclerosis Risk in Communities (ARIC) study. Participants include Black and White men and women from four U.S. communities. Baseline visits in this longitudinal cohort study began between 1987 and 1989, and follow-up included seven additional visits and regular phone calls.
The investigators identified participants with late-onset epilepsy by searching for Medicare claims related to seizures or epilepsy filed between 1991 and 2015. Those with two or more such claims and age of onset of 67 years or greater were considered to have late-onset epilepsy. Participants with preexisting conditions such as brain tumors or multiple sclerosis were excluded.
ARIC participants who presented in person for visits 2, 4, 5, and 6 underwent cognitive testing with the Delayed Word Recall Test, the Digit Symbol Substitution Test, and the Word Fluency Test.
Testing at visits 5 and 6 also included other tests, such as the Mini-Mental State Examination, the Boston Naming test, and the Wechsler Memory Scale-III. Dr. Johnson and colleagues excluded data for visit 7 from the analysis because dementia adjudication was not yet complete.
The researchers identified participants with dementia using data from visits 5 and 6 and ascertained time of dementia onset through participant and informant interviews, phone calls, and hospital discharge data. Participants also were screened for mild cognitive impairment (MCI) at visits 5 and 6.
Data were analyzed using a Cox proportional hazards model and multinomial logistic regression. In subsequent analyses, researchers adjusted the data for age, sex, race, smoking status, alcohol use, hypertension, diabetes, body mass index (BMI), APOE4 status, and prevalent stroke.
The researchers found that of 9,033 study participants, 671 had late-onset epilepsy. The late-onset epilepsy group was older at baseline (56.5 vs. 55.1 years) and more likely to have hypertension (38.9% vs. 33.3%), diabetes (16.1% vs. 9.6%), and two alleles of APOE4 genotype (3.9% vs. 2.5%), compared with those without the disorder.
In all, 1,687 participants developed dementia during follow-up. The rate of incident dementia was 41.6% in participants with late-onset epilepsy and 16.8% in participants without late-onset epilepsy. The adjusted hazard ratio of subsequent dementia in participants with late-onset epilepsy versus those without the disorder was 3.05 (95% confidence interval, 2.65-3.51).
The median time to dementia ascertainment after late-onset epilepsy was 3.66 years.
Counterintuitive finding
The relationship between late-onset epilepsy and subsequent dementia was stronger in patients without stroke. The investigators offered a possible explanation for this counterintuitive finding. “We observed an interaction between [late-onset epilepsy] and stroke, with a lower (but still substantial) association between [late-onset epilepsy] and dementia in those with a history of stroke. This may be due to the known strong association between stroke and dementia, which may wash out the contributions of [late-onset epilepsy] to cognitive impairment,” the researchers wrote.
“There may also be under-capturing of dementia diagnoses among participants with stroke in the ascertainment from [Centers for Medicare & Medicaid Services] codes, as physicians may be reluctant to make a separate code for ‘dementia’ in those with cognitive impairment after stroke,” they added.
When the researchers restricted the analysis only to participants who attended visits 5 and 6 and had late-onset epilepsy ascertainment available, they found that the relative risk ratio for dementia at visit 6 was 2.90 (95% CI, 1.22-6.92; P = .009). The RRR for MCI was 0.97 (95% CI, 0.39-2.38; P = .803). The greater functional impairment in patients with late-onset epilepsy may explain the lack of a relationship between late-onset epilepsy and MCI.
“It will be important for neurologists to be aware of the possibility of cognitive impairment following late-onset epilepsy and to check in with patients and family members to see if there are concerns,” said Dr. Johnson.
“We should also be talking about the importance of lowering other risk factors for dementia by making sure cardiovascular risk factors are controlled and encouraging physical and cognitive activity,” she added.
The results require confirmation in a clinical population, the investigators noted. In addition, future research is necessary to clarify whether seizures directly increase the risk of dementia or whether shared neuropathology between epilepsy and dementia explains the risk.
“In the near future, I plan to enroll participants with late-onset epilepsy in an observational study to better understand factors that may contribute to cognitive change. Collaborations will be key as we seek to further understand what causes these changes and what could be done to prevent them,” Dr. Johnson added.
Strengths and weaknesses
In an accompanying editorial, W. Allen Hauser, MD, professor emeritus of neurology and epidemiology at Columbia University in New York, and colleagues noted that the findings support a bidirectional relationship between dementia and epilepsy, adding that accumulation of amyloid beta peptide is a plausible underlying pathophysiology that may explain this relationship.
Future research should clarify the effect of factors such as seizure type, seizure frequency, and age of onset on the risk of dementia among patients with epilepsy, the editorialists wrote. Such investigations could help elucidate the underlying mechanisms of these conditions and help to improve treatment, they added.
Commenting on the findings, Ilo Leppik, MD, professor of neurology and pharmacy at the University of Minnesota in Minneapolis described the research as “a very well-done study by qualified researchers in the field. … For the last century, medicine has unfortunately become compartmentalized by specialty and then subspecialty. The brain and disorders of the brain do not recognize these silos. … It is not a stretch of the known science to begin to understand that epilepsy and dementia have common anatomical and physiological underpinnings.”
The long period of prospectively gathering data and the measurement of cognitive function through various modalities are among the study’s great strengths, said Dr. Leppik. However, the study’s weakness is its reliance on Medicare claims data, which mainly would reflect convulsive seizures.
“What is missing is how many persons had subtle focal-unaware seizures that may not be identified unless a careful history is taken,” said Dr. Leppik. “Thus, this study likely underestimates the frequency of epilepsy.”
Neurologists who evaluate a person with early dementia should be on the lookout for a history of subtle seizures, said Dr. Leppik. Animal studies suggest treatment with levetiracetam or brivaracetam may slow the course of dementia, and a clinical study in participants with early dementia is underway.
“Treatment with an antiseizure drug may prove to be beneficial, especially if evidence for the presence of subtle epilepsy can be found,” Dr. Leppik added.
Greater collaboration between epileptologists and dementia specialists and larger studies of antiseizure drugs are necessary, he noted. “These studies can incorporate sophisticated structural and biochemical [analyses] to better identify the relationships between brain mechanisms that likely underlie both seizures and dementia. The ultimate promise is that early treatment of seizures may alter the course of dementia,” Dr. Leppik said.
The study by Dr. Johnson and colleagues was supported by a contract from the National Institute on Aging; ARIC from the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. The authors and Dr. Leppik have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy.
“This is an exciting area, as we are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other cohort studies are finding similar results, including the Veterans’ Health Study and the Framingham Study,” she added.
The study was published online Oct. 23 in Neurology
Bidirectional relationship?
Previous research has established that dementia is a risk factor for epilepsy, but recent studies also suggest an increased risk of incident dementia among patients with adult-onset epilepsy. Several risk factors for late-onset epilepsy, including diabetes and hypertension, also are risk factors for dementia. However, the effect of late-onset epilepsy on dementia risk in patients with these comorbidities has not been clarified.
To investigate, the researchers examined data from the Atherosclerosis Risk in Communities (ARIC) study. Participants include Black and White men and women from four U.S. communities. Baseline visits in this longitudinal cohort study began between 1987 and 1989, and follow-up included seven additional visits and regular phone calls.
The investigators identified participants with late-onset epilepsy by searching for Medicare claims related to seizures or epilepsy filed between 1991 and 2015. Those with two or more such claims and age of onset of 67 years or greater were considered to have late-onset epilepsy. Participants with preexisting conditions such as brain tumors or multiple sclerosis were excluded.
ARIC participants who presented in person for visits 2, 4, 5, and 6 underwent cognitive testing with the Delayed Word Recall Test, the Digit Symbol Substitution Test, and the Word Fluency Test.
Testing at visits 5 and 6 also included other tests, such as the Mini-Mental State Examination, the Boston Naming test, and the Wechsler Memory Scale-III. Dr. Johnson and colleagues excluded data for visit 7 from the analysis because dementia adjudication was not yet complete.
The researchers identified participants with dementia using data from visits 5 and 6 and ascertained time of dementia onset through participant and informant interviews, phone calls, and hospital discharge data. Participants also were screened for mild cognitive impairment (MCI) at visits 5 and 6.
Data were analyzed using a Cox proportional hazards model and multinomial logistic regression. In subsequent analyses, researchers adjusted the data for age, sex, race, smoking status, alcohol use, hypertension, diabetes, body mass index (BMI), APOE4 status, and prevalent stroke.
The researchers found that of 9,033 study participants, 671 had late-onset epilepsy. The late-onset epilepsy group was older at baseline (56.5 vs. 55.1 years) and more likely to have hypertension (38.9% vs. 33.3%), diabetes (16.1% vs. 9.6%), and two alleles of APOE4 genotype (3.9% vs. 2.5%), compared with those without the disorder.
In all, 1,687 participants developed dementia during follow-up. The rate of incident dementia was 41.6% in participants with late-onset epilepsy and 16.8% in participants without late-onset epilepsy. The adjusted hazard ratio of subsequent dementia in participants with late-onset epilepsy versus those without the disorder was 3.05 (95% confidence interval, 2.65-3.51).
The median time to dementia ascertainment after late-onset epilepsy was 3.66 years.
Counterintuitive finding
The relationship between late-onset epilepsy and subsequent dementia was stronger in patients without stroke. The investigators offered a possible explanation for this counterintuitive finding. “We observed an interaction between [late-onset epilepsy] and stroke, with a lower (but still substantial) association between [late-onset epilepsy] and dementia in those with a history of stroke. This may be due to the known strong association between stroke and dementia, which may wash out the contributions of [late-onset epilepsy] to cognitive impairment,” the researchers wrote.
“There may also be under-capturing of dementia diagnoses among participants with stroke in the ascertainment from [Centers for Medicare & Medicaid Services] codes, as physicians may be reluctant to make a separate code for ‘dementia’ in those with cognitive impairment after stroke,” they added.
When the researchers restricted the analysis only to participants who attended visits 5 and 6 and had late-onset epilepsy ascertainment available, they found that the relative risk ratio for dementia at visit 6 was 2.90 (95% CI, 1.22-6.92; P = .009). The RRR for MCI was 0.97 (95% CI, 0.39-2.38; P = .803). The greater functional impairment in patients with late-onset epilepsy may explain the lack of a relationship between late-onset epilepsy and MCI.
“It will be important for neurologists to be aware of the possibility of cognitive impairment following late-onset epilepsy and to check in with patients and family members to see if there are concerns,” said Dr. Johnson.
“We should also be talking about the importance of lowering other risk factors for dementia by making sure cardiovascular risk factors are controlled and encouraging physical and cognitive activity,” she added.
The results require confirmation in a clinical population, the investigators noted. In addition, future research is necessary to clarify whether seizures directly increase the risk of dementia or whether shared neuropathology between epilepsy and dementia explains the risk.
“In the near future, I plan to enroll participants with late-onset epilepsy in an observational study to better understand factors that may contribute to cognitive change. Collaborations will be key as we seek to further understand what causes these changes and what could be done to prevent them,” Dr. Johnson added.
Strengths and weaknesses
In an accompanying editorial, W. Allen Hauser, MD, professor emeritus of neurology and epidemiology at Columbia University in New York, and colleagues noted that the findings support a bidirectional relationship between dementia and epilepsy, adding that accumulation of amyloid beta peptide is a plausible underlying pathophysiology that may explain this relationship.
Future research should clarify the effect of factors such as seizure type, seizure frequency, and age of onset on the risk of dementia among patients with epilepsy, the editorialists wrote. Such investigations could help elucidate the underlying mechanisms of these conditions and help to improve treatment, they added.
Commenting on the findings, Ilo Leppik, MD, professor of neurology and pharmacy at the University of Minnesota in Minneapolis described the research as “a very well-done study by qualified researchers in the field. … For the last century, medicine has unfortunately become compartmentalized by specialty and then subspecialty. The brain and disorders of the brain do not recognize these silos. … It is not a stretch of the known science to begin to understand that epilepsy and dementia have common anatomical and physiological underpinnings.”
The long period of prospectively gathering data and the measurement of cognitive function through various modalities are among the study’s great strengths, said Dr. Leppik. However, the study’s weakness is its reliance on Medicare claims data, which mainly would reflect convulsive seizures.
“What is missing is how many persons had subtle focal-unaware seizures that may not be identified unless a careful history is taken,” said Dr. Leppik. “Thus, this study likely underestimates the frequency of epilepsy.”
Neurologists who evaluate a person with early dementia should be on the lookout for a history of subtle seizures, said Dr. Leppik. Animal studies suggest treatment with levetiracetam or brivaracetam may slow the course of dementia, and a clinical study in participants with early dementia is underway.
“Treatment with an antiseizure drug may prove to be beneficial, especially if evidence for the presence of subtle epilepsy can be found,” Dr. Leppik added.
Greater collaboration between epileptologists and dementia specialists and larger studies of antiseizure drugs are necessary, he noted. “These studies can incorporate sophisticated structural and biochemical [analyses] to better identify the relationships between brain mechanisms that likely underlie both seizures and dementia. The ultimate promise is that early treatment of seizures may alter the course of dementia,” Dr. Leppik said.
The study by Dr. Johnson and colleagues was supported by a contract from the National Institute on Aging; ARIC from the National Heart, Lung, and Blood Institute; the National Institutes of Health; and the Department of Health & Human Services. The authors and Dr. Leppik have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NEUROLOGY
New cancer drugs may have saved more than 1.2 million Americans
Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.
A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.
The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.
“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.
The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.
“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
Full effect not yet observed
The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.
The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.
The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.
Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).
Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.
The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.
“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
Other factors at play
Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”
Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.
“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”
Cancer screening is not as strong an influence as it should be, Dr. Cance said.
“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.
More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.
“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”
“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”
“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”
Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.
SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.
Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.
A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.
The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.
“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.
The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.
“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
Full effect not yet observed
The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.
The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.
The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.
Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).
Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.
The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.
“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
Other factors at play
Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”
Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.
“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”
Cancer screening is not as strong an influence as it should be, Dr. Cance said.
“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.
More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.
“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”
“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”
“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”
Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.
SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.
Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.
A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.
The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.
“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.
The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.
“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
Full effect not yet observed
The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.
The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.
The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.
Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).
Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.
The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.
“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
Other factors at play
Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”
Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.
“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”
Cancer screening is not as strong an influence as it should be, Dr. Cance said.
“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.
More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.
“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”
“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”
“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”
Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.
SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.
FROM JOURNAL OF MEDICAL ECONOMICS
‘Test all patients with cancer’: One in eight have inherited mutations
These findings come from the largest study of its kind so far, conducted in nearly 3,000 patients with a wide range of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
“This study tells us that the clinical practice guidelines are not very sensitive for identifying who does or doesn’t have a genetic mutation that is predisposing them to cancer,” commented first author Niloy Jewell Samadder, MD, director of the high-risk cancer clinic at the Mayo Clinic in Phoenix.
Finding a genetic mutation can alter clinical management of the cancer.
“This really does open up treatment and management options that might not have been accessible to these patients,” Dr. Samadder emphasized.
The results were published online on Oct. 30 in JAMA Oncology and were presented simultaneously at the American Society of Human Genetics. Dr. Samadder discussed details of the study in a video posted on YouTube.
A clinician not involved in the study said the new results should lead to changes in practice.
“For cancer patients, I think the debate is over. We should test everybody,” Peter Beitsch, MD, surgical oncologist at the Dallas Surgical Group, said in an interview.
The Mayo Clinic is changing its daily practice at all four of its cancer centers. The changes will begin in the first quarter of 2021 at its Arizona campus.
“Every cancer patient who comes to Mayo Clinic will be offered genomic evaluation that includes genetic testing to identify if they have an underlying genetic mutation that predisposes to their cancer and [helps physicians decide] how to incorporate that knowledge into designing the best surgical and treatment options for that patient and their family,” Dr. Samadder said.
Study details
The study included 2,984 patients with cancer who were receiving care for a variety of solid tumor cancers at Mayo Clinic cancer centers in Arizona, Florida, Minnesota, and a community cancer center in Wisconsin.
Patients were tested for about 84 genes using next-generation sequencing provided by Invitae.
Among participants, 13.3% (n = 397) tested positive for pathogenic mutations. Of these, about 70% (282 of 397 patients) carried moderate- and high-penetrance genes that increased their risk for cancer. For almost 28.2% (n = 42) of patients with high-penetrance mutations, changes were made in treatment as a result of genetic testing. These included changes in surgical management, immunotherapy, chemotherapy, or enrollment in a clinical trial for which they may otherwise have not been eligible.
Researchers also compared their universal testing approach with targeted testing recommended in guidelines from the National Comprehensive Cancer Network, the National Society of Genetic Counselors, and the American College of Medical Genetics.
They identified pathogenic mutations in 192 patients whose mutations would have been missed using guideline-recommended criteria, such as tumor pathology or family history. This represents 6.4% of all participants in the study (192 of 2,984 patients) and 48.4% of patients who tested positive for pathogenic mutations (397 of 2,984 patients).
“Genetic testing is underutilized in cancer care, both for patients and for their families, often due to outdated guidelines that restrict testing to a narrow group of high-risk patients. All cancer patients should have access to complete genetic information that can guide their care and inform their families’ health,” coauthor Robert Nussbaum, MD, chief medical officer of Invitae, said in a statement.
Some clinicians have been pushing for genetic testing of all patients with cancer, including Dr. Beitsch, who was lead author of a similar study in breast cancer patients published last year in the Journal of Oncology. That article made waves when the authors concluded that all breast cancer patients should have expanded panel genetic testing.
This new Mayo Clinic study extends the findings in breast cancer to “all cancer patients, not just breast cancer patients,” Dr. Beitsch said in an interview.
Long-running debate
The new findings and opinions add to a long-running debate in oncology over the role of genetic testing and screening for pathogenic mutations.
Part of the debate about genetic testing has hinged on the question of costs, said Dr. Beitsch. When genetic testing first became available, it was conducted by hand, and costs were often prohibitive. Since then, genetic testing has been automated using next-generation sequencing, and the cost has decreased considerably.
“The Invitae cash price for an 80-plus gene panel is $250. That’s [the cost of] a mani-pedi in Dallas. I don’t discount that it’s a lot of money for a lot of people. Yes, it’s expensive, but it’s a lot less expensive than it used to be,” Dr. Beitsch said.
Another issue is that doctors are not entirely sure how to manage variants of uncertain significance (VUSs) when they are found. In the Mayo Clinic study, about half (47.4%; n = 1415) of participants had VUSs. The authors noted that these results are consistent with past studies.
Dr. Beitsch said that VUSs are a matter of education. To date, only about 2% of VUSs have been associated with cancer. The remainder, about 98%, do not affect treatment for patients who have already been diagnosed with cancer.
“We all have VUSs. They’re just minor variations in a gene. The vast majority of them have no consequence and don’t alter the function of the gene,” he said. “I tell everybody to ignore the VUSs [when found in patients with cancer]. Do not act on them at all. We just need to educate everybody to make sure they don’t get stressed about it.”
These comments echo guidance from the American Society of Breast Surgeons, which says that VUSs are DNA sequences that are not clinically actionable. This type of result needs to be considered as inconclusive, and patient management should not be influenced by such results.
However, VUSs are more significant if they are found in individuals who do not have cancer but who have a strong family history of cancer. In such cases, clinicians should be more aware, Dr. Beitsch emphasized.
“Patients who have a VUS and don’t have a cancer should absolutely pay more attention to their health. They got tested for a reason, and that reason is usually strong family history,” Dr. Beitsch said.
He added that a major advantage of genetic testing is that it can enable cascade genetic testing of family members. Identifying pathogenic mutations in family members can lead them to undergo screening to detect early cancers, and preventive measures can be taken that may be lifesaving.
In the Mayo Clinic study, researchers offered genetic testing to family members of patients who tested positive for a pathogenic mutation. Testing was available free of charge for up to 90 days after a participant tested positive. In addition, family members were shown an educational video.
Nevertheless, only 17.6% (n = 70) of patients with pathogenic mutations had family members who underwent testing. Among these, 45% (79 of 176) of family members who were tested were found to carry pathogenic mutations.
“This really told us that financial barriers are not the only barrier to families understanding and undergoing preventive testing,” Dr. Samadder said. “There are probably a number of other barriers – socioeconomic or emotional – that we have to deal with.”
Genetic testing was provided by Invitae. The study was supported by several grants, including a Mayo Transform the Practice Grant, and by Mayo Clinic’s Center for Individualized Medicine. Two coauthors are employees of Invitae. Dr. Beitsch reported participating in a study 2 years ago that was funded by Invitae. He currently receives no financial support from Invitae. Several authors report receiving fees from one or more of the following companies: Pfizer, Maze Therapeutics, Genome Medical, Astellas, and Merck.
This article first appeared on Medscape.com.
These findings come from the largest study of its kind so far, conducted in nearly 3,000 patients with a wide range of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
“This study tells us that the clinical practice guidelines are not very sensitive for identifying who does or doesn’t have a genetic mutation that is predisposing them to cancer,” commented first author Niloy Jewell Samadder, MD, director of the high-risk cancer clinic at the Mayo Clinic in Phoenix.
Finding a genetic mutation can alter clinical management of the cancer.
“This really does open up treatment and management options that might not have been accessible to these patients,” Dr. Samadder emphasized.
The results were published online on Oct. 30 in JAMA Oncology and were presented simultaneously at the American Society of Human Genetics. Dr. Samadder discussed details of the study in a video posted on YouTube.
A clinician not involved in the study said the new results should lead to changes in practice.
“For cancer patients, I think the debate is over. We should test everybody,” Peter Beitsch, MD, surgical oncologist at the Dallas Surgical Group, said in an interview.
The Mayo Clinic is changing its daily practice at all four of its cancer centers. The changes will begin in the first quarter of 2021 at its Arizona campus.
“Every cancer patient who comes to Mayo Clinic will be offered genomic evaluation that includes genetic testing to identify if they have an underlying genetic mutation that predisposes to their cancer and [helps physicians decide] how to incorporate that knowledge into designing the best surgical and treatment options for that patient and their family,” Dr. Samadder said.
Study details
The study included 2,984 patients with cancer who were receiving care for a variety of solid tumor cancers at Mayo Clinic cancer centers in Arizona, Florida, Minnesota, and a community cancer center in Wisconsin.
Patients were tested for about 84 genes using next-generation sequencing provided by Invitae.
Among participants, 13.3% (n = 397) tested positive for pathogenic mutations. Of these, about 70% (282 of 397 patients) carried moderate- and high-penetrance genes that increased their risk for cancer. For almost 28.2% (n = 42) of patients with high-penetrance mutations, changes were made in treatment as a result of genetic testing. These included changes in surgical management, immunotherapy, chemotherapy, or enrollment in a clinical trial for which they may otherwise have not been eligible.
Researchers also compared their universal testing approach with targeted testing recommended in guidelines from the National Comprehensive Cancer Network, the National Society of Genetic Counselors, and the American College of Medical Genetics.
They identified pathogenic mutations in 192 patients whose mutations would have been missed using guideline-recommended criteria, such as tumor pathology or family history. This represents 6.4% of all participants in the study (192 of 2,984 patients) and 48.4% of patients who tested positive for pathogenic mutations (397 of 2,984 patients).
“Genetic testing is underutilized in cancer care, both for patients and for their families, often due to outdated guidelines that restrict testing to a narrow group of high-risk patients. All cancer patients should have access to complete genetic information that can guide their care and inform their families’ health,” coauthor Robert Nussbaum, MD, chief medical officer of Invitae, said in a statement.
Some clinicians have been pushing for genetic testing of all patients with cancer, including Dr. Beitsch, who was lead author of a similar study in breast cancer patients published last year in the Journal of Oncology. That article made waves when the authors concluded that all breast cancer patients should have expanded panel genetic testing.
This new Mayo Clinic study extends the findings in breast cancer to “all cancer patients, not just breast cancer patients,” Dr. Beitsch said in an interview.
Long-running debate
The new findings and opinions add to a long-running debate in oncology over the role of genetic testing and screening for pathogenic mutations.
Part of the debate about genetic testing has hinged on the question of costs, said Dr. Beitsch. When genetic testing first became available, it was conducted by hand, and costs were often prohibitive. Since then, genetic testing has been automated using next-generation sequencing, and the cost has decreased considerably.
“The Invitae cash price for an 80-plus gene panel is $250. That’s [the cost of] a mani-pedi in Dallas. I don’t discount that it’s a lot of money for a lot of people. Yes, it’s expensive, but it’s a lot less expensive than it used to be,” Dr. Beitsch said.
Another issue is that doctors are not entirely sure how to manage variants of uncertain significance (VUSs) when they are found. In the Mayo Clinic study, about half (47.4%; n = 1415) of participants had VUSs. The authors noted that these results are consistent with past studies.
Dr. Beitsch said that VUSs are a matter of education. To date, only about 2% of VUSs have been associated with cancer. The remainder, about 98%, do not affect treatment for patients who have already been diagnosed with cancer.
“We all have VUSs. They’re just minor variations in a gene. The vast majority of them have no consequence and don’t alter the function of the gene,” he said. “I tell everybody to ignore the VUSs [when found in patients with cancer]. Do not act on them at all. We just need to educate everybody to make sure they don’t get stressed about it.”
These comments echo guidance from the American Society of Breast Surgeons, which says that VUSs are DNA sequences that are not clinically actionable. This type of result needs to be considered as inconclusive, and patient management should not be influenced by such results.
However, VUSs are more significant if they are found in individuals who do not have cancer but who have a strong family history of cancer. In such cases, clinicians should be more aware, Dr. Beitsch emphasized.
“Patients who have a VUS and don’t have a cancer should absolutely pay more attention to their health. They got tested for a reason, and that reason is usually strong family history,” Dr. Beitsch said.
He added that a major advantage of genetic testing is that it can enable cascade genetic testing of family members. Identifying pathogenic mutations in family members can lead them to undergo screening to detect early cancers, and preventive measures can be taken that may be lifesaving.
In the Mayo Clinic study, researchers offered genetic testing to family members of patients who tested positive for a pathogenic mutation. Testing was available free of charge for up to 90 days after a participant tested positive. In addition, family members were shown an educational video.
Nevertheless, only 17.6% (n = 70) of patients with pathogenic mutations had family members who underwent testing. Among these, 45% (79 of 176) of family members who were tested were found to carry pathogenic mutations.
“This really told us that financial barriers are not the only barrier to families understanding and undergoing preventive testing,” Dr. Samadder said. “There are probably a number of other barriers – socioeconomic or emotional – that we have to deal with.”
Genetic testing was provided by Invitae. The study was supported by several grants, including a Mayo Transform the Practice Grant, and by Mayo Clinic’s Center for Individualized Medicine. Two coauthors are employees of Invitae. Dr. Beitsch reported participating in a study 2 years ago that was funded by Invitae. He currently receives no financial support from Invitae. Several authors report receiving fees from one or more of the following companies: Pfizer, Maze Therapeutics, Genome Medical, Astellas, and Merck.
This article first appeared on Medscape.com.
These findings come from the largest study of its kind so far, conducted in nearly 3,000 patients with a wide range of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
“This study tells us that the clinical practice guidelines are not very sensitive for identifying who does or doesn’t have a genetic mutation that is predisposing them to cancer,” commented first author Niloy Jewell Samadder, MD, director of the high-risk cancer clinic at the Mayo Clinic in Phoenix.
Finding a genetic mutation can alter clinical management of the cancer.
“This really does open up treatment and management options that might not have been accessible to these patients,” Dr. Samadder emphasized.
The results were published online on Oct. 30 in JAMA Oncology and were presented simultaneously at the American Society of Human Genetics. Dr. Samadder discussed details of the study in a video posted on YouTube.
A clinician not involved in the study said the new results should lead to changes in practice.
“For cancer patients, I think the debate is over. We should test everybody,” Peter Beitsch, MD, surgical oncologist at the Dallas Surgical Group, said in an interview.
The Mayo Clinic is changing its daily practice at all four of its cancer centers. The changes will begin in the first quarter of 2021 at its Arizona campus.
“Every cancer patient who comes to Mayo Clinic will be offered genomic evaluation that includes genetic testing to identify if they have an underlying genetic mutation that predisposes to their cancer and [helps physicians decide] how to incorporate that knowledge into designing the best surgical and treatment options for that patient and their family,” Dr. Samadder said.
Study details
The study included 2,984 patients with cancer who were receiving care for a variety of solid tumor cancers at Mayo Clinic cancer centers in Arizona, Florida, Minnesota, and a community cancer center in Wisconsin.
Patients were tested for about 84 genes using next-generation sequencing provided by Invitae.
Among participants, 13.3% (n = 397) tested positive for pathogenic mutations. Of these, about 70% (282 of 397 patients) carried moderate- and high-penetrance genes that increased their risk for cancer. For almost 28.2% (n = 42) of patients with high-penetrance mutations, changes were made in treatment as a result of genetic testing. These included changes in surgical management, immunotherapy, chemotherapy, or enrollment in a clinical trial for which they may otherwise have not been eligible.
Researchers also compared their universal testing approach with targeted testing recommended in guidelines from the National Comprehensive Cancer Network, the National Society of Genetic Counselors, and the American College of Medical Genetics.
They identified pathogenic mutations in 192 patients whose mutations would have been missed using guideline-recommended criteria, such as tumor pathology or family history. This represents 6.4% of all participants in the study (192 of 2,984 patients) and 48.4% of patients who tested positive for pathogenic mutations (397 of 2,984 patients).
“Genetic testing is underutilized in cancer care, both for patients and for their families, often due to outdated guidelines that restrict testing to a narrow group of high-risk patients. All cancer patients should have access to complete genetic information that can guide their care and inform their families’ health,” coauthor Robert Nussbaum, MD, chief medical officer of Invitae, said in a statement.
Some clinicians have been pushing for genetic testing of all patients with cancer, including Dr. Beitsch, who was lead author of a similar study in breast cancer patients published last year in the Journal of Oncology. That article made waves when the authors concluded that all breast cancer patients should have expanded panel genetic testing.
This new Mayo Clinic study extends the findings in breast cancer to “all cancer patients, not just breast cancer patients,” Dr. Beitsch said in an interview.
Long-running debate
The new findings and opinions add to a long-running debate in oncology over the role of genetic testing and screening for pathogenic mutations.
Part of the debate about genetic testing has hinged on the question of costs, said Dr. Beitsch. When genetic testing first became available, it was conducted by hand, and costs were often prohibitive. Since then, genetic testing has been automated using next-generation sequencing, and the cost has decreased considerably.
“The Invitae cash price for an 80-plus gene panel is $250. That’s [the cost of] a mani-pedi in Dallas. I don’t discount that it’s a lot of money for a lot of people. Yes, it’s expensive, but it’s a lot less expensive than it used to be,” Dr. Beitsch said.
Another issue is that doctors are not entirely sure how to manage variants of uncertain significance (VUSs) when they are found. In the Mayo Clinic study, about half (47.4%; n = 1415) of participants had VUSs. The authors noted that these results are consistent with past studies.
Dr. Beitsch said that VUSs are a matter of education. To date, only about 2% of VUSs have been associated with cancer. The remainder, about 98%, do not affect treatment for patients who have already been diagnosed with cancer.
“We all have VUSs. They’re just minor variations in a gene. The vast majority of them have no consequence and don’t alter the function of the gene,” he said. “I tell everybody to ignore the VUSs [when found in patients with cancer]. Do not act on them at all. We just need to educate everybody to make sure they don’t get stressed about it.”
These comments echo guidance from the American Society of Breast Surgeons, which says that VUSs are DNA sequences that are not clinically actionable. This type of result needs to be considered as inconclusive, and patient management should not be influenced by such results.
However, VUSs are more significant if they are found in individuals who do not have cancer but who have a strong family history of cancer. In such cases, clinicians should be more aware, Dr. Beitsch emphasized.
“Patients who have a VUS and don’t have a cancer should absolutely pay more attention to their health. They got tested for a reason, and that reason is usually strong family history,” Dr. Beitsch said.
He added that a major advantage of genetic testing is that it can enable cascade genetic testing of family members. Identifying pathogenic mutations in family members can lead them to undergo screening to detect early cancers, and preventive measures can be taken that may be lifesaving.
In the Mayo Clinic study, researchers offered genetic testing to family members of patients who tested positive for a pathogenic mutation. Testing was available free of charge for up to 90 days after a participant tested positive. In addition, family members were shown an educational video.
Nevertheless, only 17.6% (n = 70) of patients with pathogenic mutations had family members who underwent testing. Among these, 45% (79 of 176) of family members who were tested were found to carry pathogenic mutations.
“This really told us that financial barriers are not the only barrier to families understanding and undergoing preventive testing,” Dr. Samadder said. “There are probably a number of other barriers – socioeconomic or emotional – that we have to deal with.”
Genetic testing was provided by Invitae. The study was supported by several grants, including a Mayo Transform the Practice Grant, and by Mayo Clinic’s Center for Individualized Medicine. Two coauthors are employees of Invitae. Dr. Beitsch reported participating in a study 2 years ago that was funded by Invitae. He currently receives no financial support from Invitae. Several authors report receiving fees from one or more of the following companies: Pfizer, Maze Therapeutics, Genome Medical, Astellas, and Merck.
This article first appeared on Medscape.com.
Study supports genetic testing in older women with breast cancer
according to researchers.
The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.
Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.
The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.
The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.
The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
Results may inform guidelines
National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.
“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.
He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
Current testing limits ‘ridiculous’
“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.
Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.
“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.
Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.
“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”
Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.
As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.
Study details and next steps
The study included 13,762 women with breast cancer who were older than 65 years and 12,945 age-matched controls without breast cancer. A multigene amplicon-based panel was used to identify 12 known pathogenic variants in breast cancer–predisposing genes.
The women were part of the CARRIERS consortium, which pools breast cancer patients from case-control studies. Overall, 82.6% of subjects were non-Hispanic White, 25.6% of breast cancer patients and 17.9% of control subjects had a positive family history, and the mean age was 72.8 years (range, 66-94.3 years).
Across the entire study population, 0.48% of subjects had variants in ATM, 0.18% in BRCA1, 0.49% in BRCA2, 0.67% in CHEK2, and 0.23% in PALB2.
After adjustment for age, race, and family history, pathogenic variants in BRCA1 increased the risk of cancer more than threefold (odds ratio, 3.37), with similar findings for BRCA2 (OR, 2.64), PALB2 (OR, 3.09), and CHEK2 (OR, 2.13). ATM variants were not associated with a significantly increased risk of breast cancer (OR, 1.38).
Dr. Boddicker said the researchers’ next steps are to incorporate polygenic risk scores into the analyses and further investigate the impact of race.
The study is funded by the National Institutes of Health. Dr. Boddicker and Dr. Beitsch didn’t have any disclosures.
SOURCE: Boddicker NJ et al. ASHG 2020, Abstract 2412.
according to researchers.
The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.
Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.
The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.
The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.
The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
Results may inform guidelines
National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.
“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.
He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
Current testing limits ‘ridiculous’
“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.
Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.
“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.
Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.
“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”
Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.
As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.
Study details and next steps
The study included 13,762 women with breast cancer who were older than 65 years and 12,945 age-matched controls without breast cancer. A multigene amplicon-based panel was used to identify 12 known pathogenic variants in breast cancer–predisposing genes.
The women were part of the CARRIERS consortium, which pools breast cancer patients from case-control studies. Overall, 82.6% of subjects were non-Hispanic White, 25.6% of breast cancer patients and 17.9% of control subjects had a positive family history, and the mean age was 72.8 years (range, 66-94.3 years).
Across the entire study population, 0.48% of subjects had variants in ATM, 0.18% in BRCA1, 0.49% in BRCA2, 0.67% in CHEK2, and 0.23% in PALB2.
After adjustment for age, race, and family history, pathogenic variants in BRCA1 increased the risk of cancer more than threefold (odds ratio, 3.37), with similar findings for BRCA2 (OR, 2.64), PALB2 (OR, 3.09), and CHEK2 (OR, 2.13). ATM variants were not associated with a significantly increased risk of breast cancer (OR, 1.38).
Dr. Boddicker said the researchers’ next steps are to incorporate polygenic risk scores into the analyses and further investigate the impact of race.
The study is funded by the National Institutes of Health. Dr. Boddicker and Dr. Beitsch didn’t have any disclosures.
SOURCE: Boddicker NJ et al. ASHG 2020, Abstract 2412.
according to researchers.
The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.
Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.
The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.
The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.
The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
Results may inform guidelines
National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.
“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.
He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
Current testing limits ‘ridiculous’
“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.
Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.
“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.
Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.
“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”
Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.
As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.
Study details and next steps
The study included 13,762 women with breast cancer who were older than 65 years and 12,945 age-matched controls without breast cancer. A multigene amplicon-based panel was used to identify 12 known pathogenic variants in breast cancer–predisposing genes.
The women were part of the CARRIERS consortium, which pools breast cancer patients from case-control studies. Overall, 82.6% of subjects were non-Hispanic White, 25.6% of breast cancer patients and 17.9% of control subjects had a positive family history, and the mean age was 72.8 years (range, 66-94.3 years).
Across the entire study population, 0.48% of subjects had variants in ATM, 0.18% in BRCA1, 0.49% in BRCA2, 0.67% in CHEK2, and 0.23% in PALB2.
After adjustment for age, race, and family history, pathogenic variants in BRCA1 increased the risk of cancer more than threefold (odds ratio, 3.37), with similar findings for BRCA2 (OR, 2.64), PALB2 (OR, 3.09), and CHEK2 (OR, 2.13). ATM variants were not associated with a significantly increased risk of breast cancer (OR, 1.38).
Dr. Boddicker said the researchers’ next steps are to incorporate polygenic risk scores into the analyses and further investigate the impact of race.
The study is funded by the National Institutes of Health. Dr. Boddicker and Dr. Beitsch didn’t have any disclosures.
SOURCE: Boddicker NJ et al. ASHG 2020, Abstract 2412.
FROM ASHG 2020
Genomic analysis reveals insights into pathogenesis of neuroblastoma
Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.
“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.
The group’s findings were published in Nature Communications.
The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.
The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).
MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).
“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.
Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.
Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.
“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.
Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.
“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.
SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.
Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.
“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.
The group’s findings were published in Nature Communications.
The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.
The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).
MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).
“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.
Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.
Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.
“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.
Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.
“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.
SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.
Insights into the genetic drivers of the disease were identified based on data from whole-genome, whole-exome, and/or transcriptome sequencing of tumor samples.
“The comprehensive genome-wide analysis performed here allowed us to discover age-associated alterations in MYCN, TERT, PTPRD, and Ras pathway alterations, which, together with ATRX, represent the majority of common driver gene alterations in neuroblastoma,” wrote study author Samuel W. Brady, PhD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues.
The group’s findings were published in Nature Communications.
The researchers integrated and analyzed data from 702 neuroblastomas encompassing all age and risk categories, with the goal of identifying rare driver events and age-related molecular aberrations. Among the samples, 23 were from patients who had relapsed.
The researchers found that 40% of samples had somatic alterations in known driver genes, with the most common alterations being MYCN (19%; primarily amplification), TERT (17%; structural variations [SVs]), SHANK2 (13%; SVs), PTPRD (11%; SVs and focal deletions), ALK (10%; single nucleotide variants [SNVs] and SVs), and ATRX (8%; multiple mutation types).
MYCN and TERT alterations were more common in younger children (median age of 2.3 years and 3.8 years, respectively), while ATRX alterations were more frequently seen in older patients (median age of 5.6 years).
“These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models,” the researchers wrote.
Furthermore, they found evidence to suggest the COSMIC mutational signature 18 is the most common cause of driver SNVs in neuroblastoma, including most Ras-activating and ALK variants.
Signature 18 was enriched in neuroblastomas with increased expression of mitochondrial ribosome and electron transport–associated genes, 17q gain, and MYCN amplification.
“[T]his mutagenic process, which is caused by ROS [reactive oxygen species] in other settings (though not proven in neuroblastoma), may promote evolution and heterogeneity, as many driver SNVs, such as ALK mutations, are later events in neuroblastoma,” the researchers explained.
Based on these findings, the authors concluded that neuroblastomas with 17q gain may be amenable to precision medicines, possibly through targeting altered mitochondrial function.
“[Our] findings will identify patients who might be eligible for targeted therapy and those that may be at higher risk based on a combination of genetic alterations detected by these genome-wide sequencing methods,” commented study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital. One author disclosed financial affiliations with Y-mabs Therapeutics, Abpro-Labs, Eureka Therapeutics, and Biotec Pharmacon.
SOURCE: Brady SW et al. Nat Commun. 2020 Oct 14. doi: 10.1038/s41467-020-18987-4.
FROM NATURE COMMUNICATIONS