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Despite risks and warnings, CNS polypharmacy is prevalent among patients with dementia
, new research suggests.
Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.
“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.
The study was published online March 9 in JAMA.
Serious risks
Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.
They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”
The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.
They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.
To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.
The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.
They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
Conservative approach warranted
Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.
There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.
Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.
Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.
The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.
Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.
“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.
Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.
In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
A major clinical challenge
Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”
Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.
Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.
“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.
Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.
The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.
“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.
The study was published online March 9 in JAMA.
Serious risks
Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.
They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”
The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.
They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.
To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.
The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.
They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
Conservative approach warranted
Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.
There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.
Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.
Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.
The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.
Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.
“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.
Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.
In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
A major clinical challenge
Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”
Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.
Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.
“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.
Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.
The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.
“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.
The study was published online March 9 in JAMA.
Serious risks
Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.
They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”
The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.
They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.
To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.
The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.
They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
Conservative approach warranted
Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.
There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.
Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.
Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.
The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.
Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.
“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.
Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.
In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
A major clinical challenge
Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”
Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.
Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.
“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.
Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.
The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA
Don’t delay: Cancer patients need both doses of COVID vaccine
The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.
Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.
The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).
This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.
The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).
The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.
Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.
“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.
“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.
The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.
These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.
“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”
Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.
Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.
“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”
Study details
Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.
There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”
To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.
The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.
The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.
All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.
The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.
The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).
T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.
Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.
Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.
The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.
Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.
The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).
This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.
The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).
The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.
Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.
“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.
“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.
The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.
These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.
“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”
Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.
Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.
“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”
Study details
Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.
There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”
To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.
The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.
The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.
All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.
The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.
The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).
T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.
Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.
Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.
The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.
Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.
The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).
This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.
The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).
The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.
Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.
“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.
“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.
The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.
These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.
“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”
Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.
Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.
“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”
Study details
Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.
There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”
To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.
The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.
The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.
All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.
The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.
The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).
T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.
Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.
Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.
The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
mCODE: Improving data sharing to enhance cancer care
An initiative designed to improve sharing of patient data may provide “tremendous benefits” in cancer care and research, according to authors of a review article.
The goals of the initiative, called Minimal Common Oncology Data Elements (mCODE), were to identify the data elements in electronic health records that are “essential” for making treatment decisions and create “a standardized computable data format” that would improve the exchange of data across EHRs, according to the mCODE website.
Travis J. Osterman, DO, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues described the mCODE initiative in a review published in JCO Clinical Cancer Informatics.
At present, commercially available EHRs are poorly designed to support modern oncology workflow, requiring laborious data entry and lacking a common library of oncology-specific discrete data elements. As an example, most EHRs poorly support the needs of precision oncology and clinical genetics, since next-generation sequencing and genetic test results are almost universally reported in PDF files.
In addition, basic, operational oncology data (e.g., cancer staging, adverse event documentation, response to treatment, etc.) are captured in EHRs primarily as an unstructured narrative.
Computable, analytical data are found for only the small percentage of patients in clinical trials. Even then, some degree of manual data abstraction is regularly required.
Interoperability of EHRs between practices and health care institutions is often so poor that the transfer of basic cancer-related information as analyzable data is difficult or even impossible.
Making progress: The 21st Century Cures Act
The American Society of Clinical Oncology has a more than 15-year history of developing oncology data standards. Unfortunately, progress in implementing these standards has been glacially slow. Impediments have included:
- A lack of conformance with clinical workflows.
- Failure to test standards on specific-use cases during pilot testing.
- A focus on data exchange, rather than the practical impediments to data entry.
- Poor engagement with EHR vendors in distributing clinical information modules with an oncology-specific focus
- Instability of data interoperability technologies.
The 21st Century Cures Act, which became law in December 2016, mandated improvement in the interoperability of health information through the development of data standards and application programming interfaces.
In early 2020, final rules for implementation required technology vendors to employ application programming interfaces using a single interoperability resource. In addition, payers were required to use the United States Core Data for Interoperability Standard for data exchange. These requirements were intended to provide patients with access to their own health care data “without special effort.”
As a fortunate byproduct, since EHR vendors are required to implement application program interfaces using the Health Level Seven International (HL7) Fast Healthcare Interoperability Resource (FHIR) Specification, the final rules could enable systems like mCODE to be more easily integrated with existing EHRs.
Lessons from CancerLinQ
ASCO created the health technology platform CancerLinQ in 2014, envisioning that it could become an oncology-focused learning health system – a system in which internal data and experience are systematically integrated with external evidence, allowing knowledge to be put into practice.
CancerLinQ extracts data from EHRs and other sources via direct software connections. CancerLinQ then aggregates, harmonizes, and normalizes the data in a cloud-based environment.
The data are available to participating practices for quality improvement in patient care and secondary research. In 2020, records of cancer patients in the CancerLinQ database surpassed 2 million.
CancerLinQ has been successful. However, because of the nature of the EHR ecosystem and the scope and variability of data capture by clinicians, supporting a true learning health system has proven to be a formidable task. Postprocessing manual review using trained human curators is laborious and unsustainable.
The CancerLinQ experience illustrated that basic cancer-pertinent data should be standardized in the EHR and collected prospectively.
The mCODE model
The mCODE initiative seeks to facilitate progress in care quality, clinical research, and health care policy by developing and maintaining a standard, computable, interoperable data format.
Guiding principles that were adopted early in mCODE’s development included:
- A collaborative, noncommercial, use case–driven developmental model.
- Iterative processes.
- User-driven development, refinement, and maintenance.
- Low ongoing maintenance requirements.
A foundational moment in mCODE’s development involved achieving consensus among stakeholders that the project would fail if EHR vendors required additional data entry by users.
After pilot work, a real-world endpoints project, working-group deliberation, public comment, and refinement, the final data standard included six primary domains: patient, disease, laboratory data/vital signs, genomics, treatment, and outcome.
Each domain is further divided into several concepts with specific associated data elements. The data elements are modeled into value sets that specify the possible values for the data element.
To test mCODE, eight organizations representing oncology EHR vendors, standards developers, and research organizations participated in a cancer interoperability track. The comments helped refine mCODE version 1.0, which was released in March 2020 and is accessible via the mCODE website.
Additions will likely be reviewed by a technical review group after external piloting of new use cases.
Innovation, not regulation
Every interaction between a patient and care provider yields information that could lead to improved safety and better outcomes. To be successful, the information must be collected in a computable format so it can be aggregated with data from other patients, analyzed without manual curation, and shared through interoperable systems. Those data should also be secure enough to protect the privacy of individual patients.
mCODE is a consensus data standard for oncology that provides an infrastructure to share patient data between oncology practices and health care systems while promising little to no additional data entry on the part of clinicians. Adoption by sites will be critical, however.
Publishing the standard through the HL7 FHIR technology demonstrated to EHR vendors and regulatory agencies the stability of HL7, an essential requirement for its incorporation into software.
EHR vendors and others are engaged in the CodeX HL7 FHIR Accelerator to design projects to expand and/or modify mCODE. Their creativity and innovativeness via the external advisory mCODE council and/or CodeX will be encouraged to help mCODE reach its full potential.
As part of CodeX, the Community of Practice, an open forum for end users, was established to provide regular updates about mCODE-related initiatives and use cases to solicit in-progress input, according to Robert S. Miller, MD, medical director of CancerLinQ and an author of the mCODE review.
For mCODE to be embraced by all stakeholders, there should be no additional regulations. By engaging stakeholders in an enterprise that supports innovation and collaboration – without additional regulation – mCODE could maximize the potential of EHRs that, until now, have assisted us only marginally in accomplishing those goals.
mCODE is a joint venture of ASCO/CancerLinQ, the Alliance for Clinical Trials in Oncology Foundation, the MITRE Corporation, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Osterman disclosed a grant from the National Cancer Institute and relationships with Infostratix, eHealth, AstraZeneca, Outcomes Insights, Biodesix, MD Outlook, GenomOncology, Cota Healthcare, GE Healthcare, and Microsoft. Dr. Miller and the third review author disclosed no conflicts of interest.
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.
An initiative designed to improve sharing of patient data may provide “tremendous benefits” in cancer care and research, according to authors of a review article.
The goals of the initiative, called Minimal Common Oncology Data Elements (mCODE), were to identify the data elements in electronic health records that are “essential” for making treatment decisions and create “a standardized computable data format” that would improve the exchange of data across EHRs, according to the mCODE website.
Travis J. Osterman, DO, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues described the mCODE initiative in a review published in JCO Clinical Cancer Informatics.
At present, commercially available EHRs are poorly designed to support modern oncology workflow, requiring laborious data entry and lacking a common library of oncology-specific discrete data elements. As an example, most EHRs poorly support the needs of precision oncology and clinical genetics, since next-generation sequencing and genetic test results are almost universally reported in PDF files.
In addition, basic, operational oncology data (e.g., cancer staging, adverse event documentation, response to treatment, etc.) are captured in EHRs primarily as an unstructured narrative.
Computable, analytical data are found for only the small percentage of patients in clinical trials. Even then, some degree of manual data abstraction is regularly required.
Interoperability of EHRs between practices and health care institutions is often so poor that the transfer of basic cancer-related information as analyzable data is difficult or even impossible.
Making progress: The 21st Century Cures Act
The American Society of Clinical Oncology has a more than 15-year history of developing oncology data standards. Unfortunately, progress in implementing these standards has been glacially slow. Impediments have included:
- A lack of conformance with clinical workflows.
- Failure to test standards on specific-use cases during pilot testing.
- A focus on data exchange, rather than the practical impediments to data entry.
- Poor engagement with EHR vendors in distributing clinical information modules with an oncology-specific focus
- Instability of data interoperability technologies.
The 21st Century Cures Act, which became law in December 2016, mandated improvement in the interoperability of health information through the development of data standards and application programming interfaces.
In early 2020, final rules for implementation required technology vendors to employ application programming interfaces using a single interoperability resource. In addition, payers were required to use the United States Core Data for Interoperability Standard for data exchange. These requirements were intended to provide patients with access to their own health care data “without special effort.”
As a fortunate byproduct, since EHR vendors are required to implement application program interfaces using the Health Level Seven International (HL7) Fast Healthcare Interoperability Resource (FHIR) Specification, the final rules could enable systems like mCODE to be more easily integrated with existing EHRs.
Lessons from CancerLinQ
ASCO created the health technology platform CancerLinQ in 2014, envisioning that it could become an oncology-focused learning health system – a system in which internal data and experience are systematically integrated with external evidence, allowing knowledge to be put into practice.
CancerLinQ extracts data from EHRs and other sources via direct software connections. CancerLinQ then aggregates, harmonizes, and normalizes the data in a cloud-based environment.
The data are available to participating practices for quality improvement in patient care and secondary research. In 2020, records of cancer patients in the CancerLinQ database surpassed 2 million.
CancerLinQ has been successful. However, because of the nature of the EHR ecosystem and the scope and variability of data capture by clinicians, supporting a true learning health system has proven to be a formidable task. Postprocessing manual review using trained human curators is laborious and unsustainable.
The CancerLinQ experience illustrated that basic cancer-pertinent data should be standardized in the EHR and collected prospectively.
The mCODE model
The mCODE initiative seeks to facilitate progress in care quality, clinical research, and health care policy by developing and maintaining a standard, computable, interoperable data format.
Guiding principles that were adopted early in mCODE’s development included:
- A collaborative, noncommercial, use case–driven developmental model.
- Iterative processes.
- User-driven development, refinement, and maintenance.
- Low ongoing maintenance requirements.
A foundational moment in mCODE’s development involved achieving consensus among stakeholders that the project would fail if EHR vendors required additional data entry by users.
After pilot work, a real-world endpoints project, working-group deliberation, public comment, and refinement, the final data standard included six primary domains: patient, disease, laboratory data/vital signs, genomics, treatment, and outcome.
Each domain is further divided into several concepts with specific associated data elements. The data elements are modeled into value sets that specify the possible values for the data element.
To test mCODE, eight organizations representing oncology EHR vendors, standards developers, and research organizations participated in a cancer interoperability track. The comments helped refine mCODE version 1.0, which was released in March 2020 and is accessible via the mCODE website.
Additions will likely be reviewed by a technical review group after external piloting of new use cases.
Innovation, not regulation
Every interaction between a patient and care provider yields information that could lead to improved safety and better outcomes. To be successful, the information must be collected in a computable format so it can be aggregated with data from other patients, analyzed without manual curation, and shared through interoperable systems. Those data should also be secure enough to protect the privacy of individual patients.
mCODE is a consensus data standard for oncology that provides an infrastructure to share patient data between oncology practices and health care systems while promising little to no additional data entry on the part of clinicians. Adoption by sites will be critical, however.
Publishing the standard through the HL7 FHIR technology demonstrated to EHR vendors and regulatory agencies the stability of HL7, an essential requirement for its incorporation into software.
EHR vendors and others are engaged in the CodeX HL7 FHIR Accelerator to design projects to expand and/or modify mCODE. Their creativity and innovativeness via the external advisory mCODE council and/or CodeX will be encouraged to help mCODE reach its full potential.
As part of CodeX, the Community of Practice, an open forum for end users, was established to provide regular updates about mCODE-related initiatives and use cases to solicit in-progress input, according to Robert S. Miller, MD, medical director of CancerLinQ and an author of the mCODE review.
For mCODE to be embraced by all stakeholders, there should be no additional regulations. By engaging stakeholders in an enterprise that supports innovation and collaboration – without additional regulation – mCODE could maximize the potential of EHRs that, until now, have assisted us only marginally in accomplishing those goals.
mCODE is a joint venture of ASCO/CancerLinQ, the Alliance for Clinical Trials in Oncology Foundation, the MITRE Corporation, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Osterman disclosed a grant from the National Cancer Institute and relationships with Infostratix, eHealth, AstraZeneca, Outcomes Insights, Biodesix, MD Outlook, GenomOncology, Cota Healthcare, GE Healthcare, and Microsoft. Dr. Miller and the third review author disclosed no conflicts of interest.
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.
An initiative designed to improve sharing of patient data may provide “tremendous benefits” in cancer care and research, according to authors of a review article.
The goals of the initiative, called Minimal Common Oncology Data Elements (mCODE), were to identify the data elements in electronic health records that are “essential” for making treatment decisions and create “a standardized computable data format” that would improve the exchange of data across EHRs, according to the mCODE website.
Travis J. Osterman, DO, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues described the mCODE initiative in a review published in JCO Clinical Cancer Informatics.
At present, commercially available EHRs are poorly designed to support modern oncology workflow, requiring laborious data entry and lacking a common library of oncology-specific discrete data elements. As an example, most EHRs poorly support the needs of precision oncology and clinical genetics, since next-generation sequencing and genetic test results are almost universally reported in PDF files.
In addition, basic, operational oncology data (e.g., cancer staging, adverse event documentation, response to treatment, etc.) are captured in EHRs primarily as an unstructured narrative.
Computable, analytical data are found for only the small percentage of patients in clinical trials. Even then, some degree of manual data abstraction is regularly required.
Interoperability of EHRs between practices and health care institutions is often so poor that the transfer of basic cancer-related information as analyzable data is difficult or even impossible.
Making progress: The 21st Century Cures Act
The American Society of Clinical Oncology has a more than 15-year history of developing oncology data standards. Unfortunately, progress in implementing these standards has been glacially slow. Impediments have included:
- A lack of conformance with clinical workflows.
- Failure to test standards on specific-use cases during pilot testing.
- A focus on data exchange, rather than the practical impediments to data entry.
- Poor engagement with EHR vendors in distributing clinical information modules with an oncology-specific focus
- Instability of data interoperability technologies.
The 21st Century Cures Act, which became law in December 2016, mandated improvement in the interoperability of health information through the development of data standards and application programming interfaces.
In early 2020, final rules for implementation required technology vendors to employ application programming interfaces using a single interoperability resource. In addition, payers were required to use the United States Core Data for Interoperability Standard for data exchange. These requirements were intended to provide patients with access to their own health care data “without special effort.”
As a fortunate byproduct, since EHR vendors are required to implement application program interfaces using the Health Level Seven International (HL7) Fast Healthcare Interoperability Resource (FHIR) Specification, the final rules could enable systems like mCODE to be more easily integrated with existing EHRs.
Lessons from CancerLinQ
ASCO created the health technology platform CancerLinQ in 2014, envisioning that it could become an oncology-focused learning health system – a system in which internal data and experience are systematically integrated with external evidence, allowing knowledge to be put into practice.
CancerLinQ extracts data from EHRs and other sources via direct software connections. CancerLinQ then aggregates, harmonizes, and normalizes the data in a cloud-based environment.
The data are available to participating practices for quality improvement in patient care and secondary research. In 2020, records of cancer patients in the CancerLinQ database surpassed 2 million.
CancerLinQ has been successful. However, because of the nature of the EHR ecosystem and the scope and variability of data capture by clinicians, supporting a true learning health system has proven to be a formidable task. Postprocessing manual review using trained human curators is laborious and unsustainable.
The CancerLinQ experience illustrated that basic cancer-pertinent data should be standardized in the EHR and collected prospectively.
The mCODE model
The mCODE initiative seeks to facilitate progress in care quality, clinical research, and health care policy by developing and maintaining a standard, computable, interoperable data format.
Guiding principles that were adopted early in mCODE’s development included:
- A collaborative, noncommercial, use case–driven developmental model.
- Iterative processes.
- User-driven development, refinement, and maintenance.
- Low ongoing maintenance requirements.
A foundational moment in mCODE’s development involved achieving consensus among stakeholders that the project would fail if EHR vendors required additional data entry by users.
After pilot work, a real-world endpoints project, working-group deliberation, public comment, and refinement, the final data standard included six primary domains: patient, disease, laboratory data/vital signs, genomics, treatment, and outcome.
Each domain is further divided into several concepts with specific associated data elements. The data elements are modeled into value sets that specify the possible values for the data element.
To test mCODE, eight organizations representing oncology EHR vendors, standards developers, and research organizations participated in a cancer interoperability track. The comments helped refine mCODE version 1.0, which was released in March 2020 and is accessible via the mCODE website.
Additions will likely be reviewed by a technical review group after external piloting of new use cases.
Innovation, not regulation
Every interaction between a patient and care provider yields information that could lead to improved safety and better outcomes. To be successful, the information must be collected in a computable format so it can be aggregated with data from other patients, analyzed without manual curation, and shared through interoperable systems. Those data should also be secure enough to protect the privacy of individual patients.
mCODE is a consensus data standard for oncology that provides an infrastructure to share patient data between oncology practices and health care systems while promising little to no additional data entry on the part of clinicians. Adoption by sites will be critical, however.
Publishing the standard through the HL7 FHIR technology demonstrated to EHR vendors and regulatory agencies the stability of HL7, an essential requirement for its incorporation into software.
EHR vendors and others are engaged in the CodeX HL7 FHIR Accelerator to design projects to expand and/or modify mCODE. Their creativity and innovativeness via the external advisory mCODE council and/or CodeX will be encouraged to help mCODE reach its full potential.
As part of CodeX, the Community of Practice, an open forum for end users, was established to provide regular updates about mCODE-related initiatives and use cases to solicit in-progress input, according to Robert S. Miller, MD, medical director of CancerLinQ and an author of the mCODE review.
For mCODE to be embraced by all stakeholders, there should be no additional regulations. By engaging stakeholders in an enterprise that supports innovation and collaboration – without additional regulation – mCODE could maximize the potential of EHRs that, until now, have assisted us only marginally in accomplishing those goals.
mCODE is a joint venture of ASCO/CancerLinQ, the Alliance for Clinical Trials in Oncology Foundation, the MITRE Corporation, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Osterman disclosed a grant from the National Cancer Institute and relationships with Infostratix, eHealth, AstraZeneca, Outcomes Insights, Biodesix, MD Outlook, GenomOncology, Cota Healthcare, GE Healthcare, and Microsoft. Dr. Miller and the third review author disclosed no conflicts of interest.
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 JCO CLINICAL CANCER INFORMATICS
Is there liability if you don’t test for BRCA?
CASE Young woman with family history of breast cancer detects lump
Two weeks after noting a lump on her breast when her cat happened to jump on her in that spot, a 28-year-old woman (G0) went to her primary care provider. She was referred to her gynecologist; breast imaging, ultrasonography, and mammography were obtained, with microcalcifications noted. A fine needle aspiration diagnosed intraductal malignancy. The surgical breast tissue specimen was estrogen receptor (ER)- and progestogen receptor (PR)-positive and HER2-negative. Other tumor markers were obtained, including carcinoembryonic antigen, and tissue polypeptide specific antigen, p53, cathepsin D, cyclin E, and nestin, but results were not available.
With regard to family history, the woman’s mother and maternal grandmother had a history of breast cancer. The patient and her family underwent gene testing. The patient was found to be BRCA1- and BRCA2-positive; her mother was BRCA1-positive, an older sister was BRCA2-positive, and her grandmother was not tested.
The question arose in light of her family history as to why she was not tested for BRCA and appropriately counseled by her gynecologist prior to the cancer diagnosis. Litigation was initiated. While the case did not go forward regarding litigation, it is indeed a case in point. (Please note that this is a hypothetical case. It is based on a composite of several cases.)
Medical considerations
Breast cancer is the most common type of cancer affecting women in the Western world.1 Advances in clinical testing for gene mutations have escalated and allowed for identification of patients at increased risk for breast and ovarian cancer. Along with these advances come professional liability risk. After looking at the medical considerations for BRCA1 and 2 testing, we will consider a number of important legal issues. In the view of some commentators, the failure to diagnose genetic mutations in patients predisposed to cancer is “poised to become the next wave of medical professional liability lawsuits.”2
BRCA1 and BRCA2 genes provide tumor suppressor proteins, and assessment for mutations is recommended for individuals at high risk for breast and/or ovarian cancer; mutations in BRCA genes cause DNA damage, which increases the chance of developing cancer. The other way to look at it is, BRCA1 and 2 are tumor suppressor genes that are integrally involved with DNA damage control. Once there is a mutation, it adversely affects the beneficial effects of the gene. Mutations in these genes account for 5% to 10% of all hereditary breast cancers.3 Of note, men with BRCA2 are at increased risk for prostate cancer.
A patient who presents to her gynecologist stating that there is a family history of breast cancer, without knowledge of genetic components, presents a challenge (and a medicolegal risk) for the provider to assess. Prediction models have been used to determine specific patient risk for carrying a genetic mutation with resultant breast cancer development.4 Risk prediction models do not appear to be a good answer to predicting who is more likely to develop breast or ovarian cancer, however. A Mayo model may assist (FIGURE).5 Clinicians should also be aware of other models of risk assessment, including the Gail Model (TABLE 1).6
Continue to: Guidelines for genetic testing...
Guidelines for genetic testing
The American College of Obstetricians and Gynecologists states that patient medical history and family history are paramount in obtaining information regarding risk for breast and ovarian cancer. First- and second-degree relatives are allocated to this category. Information regarding age of diagnosis, maternal and paternal lineage, and ethnic background can imply a need for genetic testing (TABLE 2).7,8 A number of genetics national organizations have participated in recommendations and include the American College of Medical Genetics and Genomics, the National Society for Genetic Counselors, and the Society of Gynecologic Oncology.7
The question always surfaces, could the clinical outcome of the cancer when diagnosed have been changed if screening were undertaken, with earlier diagnosis, or prevented with prophylactic mastectomy, and changed the end result. In addition, it is well known that breast augmentation mammoplasty alters the ability to accurately evaluate mammograms. Patients considering this type of plastic surgery, ideally, should be counselled accordingly.9
Bottom line, we as clinicians must be cognizant of both ACOG and United States Preventive Services Task Force (USPSTF) recommendations regarding screening and gene testing for women considered high risk for breast cancer based on family history.7
Legal considerations
The case presented demonstrates that the discovery of the BRCA1 and BRCA2 genes, and reliable tests for determining the existence of the genes, brought with them legal issues as well as medical advantages. We look at professional liability (malpractice) questions this technology raises, and then consider the outcome of the hypothetical case. (BRCA is used here to apply broadly—not only to BRCA1 and 2 but also to PALB2, CHEK2, and similar genetic abnormalities.)
To date, the most visible BRCA legal issues covered in cases and law reviews have focused more on patent law than malpractice. The most important of these was a decision of the US Supreme Court in Association for Molecular Pathology v Myriad Genetics.10 The US Patent Office was granting patents to companies finding useful, naturally occurring segments of human DNA, and had granted Myriad several patents on BRCA1 and BRCA2 genes. This patent policy had the potential to seriously interfere with broad scientific use of these genes.11 Fortunately, the Supreme Court stepped in and unanimously invalidated such patents. It held that a “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” The Court noted, “Finding the location of the BRCA1 and BRCA2 genes does not render the genes patent eligible ‘new . . . composition[s] of matter.’”8 The Court did allow the patenting of tests for specific gene structures, and artificial changes in naturally occurring genes.
Malpractice and BRCA
While the BRCA patent wars have lingered, the potential for a significant increase in BRCA-related malpractice cases is of increasing concern. Like most malpractice liability, these new claims are based on very old principles of negligence.12 To prevail, the plaintiff (ordinarily, an injured patient) must demonstrate 4 things:
- A duty. That is, the physician owed a duty to the injured party. Usually (but not always) that requires a professional relationship between the physician and the person injured.
- A breach of that duty. Malpractice liability is based on the fact that the physician did something that a reasonably careful physician (generally, of the same specialty) would not have done, or that the physician failed to do something that a reasonable physician would have done. This usually means that the profession itself sees what the physician did (or did not do) as medically inappropriate. In medical malpractice cases, that is ordinarily measured by what the usual or common practice is among prudent physicians. In rare circumstances, courts have found the standard practice of a profession to be negligent. Where, for example, it was custom for a professional not to give an eye pressure test to anyone under age 40, a court found that common standard to be inappropriate.13 In the words of Judge Learned Hand (speaking about a different case), “a whole calling may have unduly lagged in the adoption of new and available devices. It never may set its own tests.”14 Underlying negligence is a cost-benefit analysis (discussed below).
- Damages. There must have been some damage that courts recognize, usually loss of money or opportunity to work, the cost of care, pain and suffering, or loss of enjoyment/quality of life. In malpractice, many states now recognize the “loss of chance” or the “loss of a chance.” That means, if a “physician negligently fails to diagnose a curable disease, and the patient is harmed by the disease, the physician should be liable for causing the ‘loss of a chance of a cure.’”15 (Delay in diagnosis is the most common reason for claims in breast cancer care.)16
- Causation. The breach of duty (negligence) must have caused the damages. The causation must have been reasonably close. If a driver drives through a stop sign, or a physician misreads a test, and someone is injured but there is no connection between the negligence and the injury, there is not tort liability.
The 4 elements of malpractice just described are raised in some way in the possible liability associated with BRCA testing. We next look at the ways in which liability may arise from that testing (or lack of it).
Underlying much of the following discussion is the “cost-benefit” consideration noted above. This concept is that the total cost (financial and health) of testing should be compared with the value of the benefits of testing, taking into account the probabilities that the testing will result in better health outcomes. BRCA testing, for example, is essentially cost-free in terms of physical risk. Its financial cost, while not trivial, is not great, and it is commonly covered by health insurance.17 In terms of benefits, the testing has the potential for providing critical information in making treatment decisions for a meaningful percentage of patients and their families. There are many ways of analyzing the liability risks of genetic malpractice,7,18 and the following is intended to discuss some of the greatest risks related to BRCA testing.
Continue to: Areas of liability...
Areas of liability
The failure to recommend a test. The circumstances in which BRCA testing should be undertaken are set out by professional organizations (noted above). These recommendations are not static, however. They change from time to time. Given the potential harm caused by the failure to test in relevant circumstances, malpractice liability is certainly a possibility when the failure to recommend a test to a patient results in a cancer that might have been prevented had the genetic problem been identified in a timely manner. The circumstances in which testing should be considered continue to change, placing an obligation on clinicians to stay well informed of changing genetic understandings. Another risk is that one specialist may assume that it is the job of another specialist to order the test. Whatever the cause of the failure to test, or unnecessary delay in testing, it appears to be the primary basis for BRCA liability.
The failure to properly interpret a test. Any test that is misinterpreted may lead to harm for the patient. A false negative, of course, may mean that preventive treatment that could have been undertaken will be foregone, as a “loss of a chance.” On the other hand, a false positive can lead to radical, unnecessary surgery or treatment. If a misinterpretation occurred because of carelessness by the testing organization, or confusion by a practitioner, there is a likelihood of negligence.19
A different form of “misinterpretation” could be reasonable—and not negligent. Advances in scientific-medical understanding may result in the outcome of tests being reconsidered and changed. That has been the case with genetic testing and breast cancer. The availability of multiple breast cancer SNPs (single nucleotide polymorphisms), and combining this information with other risk factors for example, results in a polygenic risk score that may be at odds with the level of risk from earlier testing.20,21 This naturally leads to the question of when later, updated testing should be recommended to look for a better current interpretation.22,23
The failure to act on BRCA test results. Testing is of no value, of course, if the results are not used properly. Test results or analyses that are not sent to the proper physicians, or are somehow ignored when properly directed, is a “never” event—it should never happen. It almost always would be considered negligence, and if the patient were injured, could lead to liability. Amazingly, one study found that, in genetic testing liability cases, nearly 20% of the claims arose from failure to return test results to patients.24 In addition, when a patient is found to be BRCA-positive, there is an obligation to discuss the options for dealing with the increased risk associated with the gene mutation(s), as well as to recommend the prudent course of action or to refer the patient to someone who will have that discussion.
Informed consent to the patient. BRCA testing requires informed consent. The physical risks of the testing process are minimal, of course, but it carries a number of other emotional and family risks. The informed consent process is an invitation to an honest discussion between clinicians and patients. It should be an opportunity to discuss what the testing is, and is not, and what the test may mean for treatment. It may also be an opportunity to discuss the implications for other members of the patient’s family (noted below).
One element of informed consent is a discussion of the consequences of failure to consent, or to undertake one of the alternatives. In the case of BRCA testing, this is especially important in cases in which a patient expresses a hesitancy to be tested with an “I’d rather not know philosophy.” Although clinicians should not practice law, some patient concerns about discrimination may be addressed by the protection that the federal Genetic Information Nondiscrimination Act (GINA) and other laws provide (which prohibit insurance and employment discrimination based on genetic information). A good source of information about GINA and related nondiscrimination laws is provided by the National Human Genome Research Institute.25 In addition, the National Institutes of Health has a website that may be helpful to many patients26 (and a much more complex site for health professionals).27 At the same time, courts have resisted plaintiffs/patients who have tried to use informed consent as a way of suing for failure to offer genetic testing.28,29
The failure to refer. In some cases, a patient should be formally referred for genetics consultation. The considerations here are similar to other circumstances in modern, fast developing medical practice that require special sensitivity to those occasions in which a patient will benefit from additional expertise. It is a principle that the AMA Council on Ethical and Judicial Affairs has expressed this way: “In the absence of adequate expertise in pretest and posttest counseling, a physician should refer the patient to an appropriate specialist.”30 The failure to refer, when that deviates from acceptable practice, may result in liability.
Informing others. BRCA testing is an area of medicine in which results may be of great significance not only to the patient but also to the patient’s family.31 Physicians should counsel patients on the importance of informing relatives about relevant results and “should make themselves available to assist patients in communicating with relatives to discuss opportunities for counseling and testing, as appropriate.”30 The question may arise, however, of whether in some circumstances physicians should go a step further in ensuring relatives receive important information regarding their loved one’s health.32 The law has been reluctant to impose liability to “third parties” (someone not a patient). Duties usually arise through the physician-patient relationship. There are exceptions. Perhaps the best known has been the obligation of mental health professionals to take action to protect third parties from patients who have made believable threats against identifiable victims.33 There are indications that some courts could find, in extreme circumstances, a “duty to warn” nonpatients in some instances where it is essential to inform third parties that they should receive a specific form of genetic testing.34,35 Such a duty would, of course, have to protect the privacy rights of the patient to the maximum extent possible. A general duty of this type has not been established widely, but may be part of the future.
Continue to: Was there liability in our example case?...
Was there liability in our example case?
The hypothetical case provided above suggests that there could be liability. Routine medical history by the primary care physician would have produced the fact that the patient’s mother, sister, and maternal grandmother had breast cancer. That would clearly have put her in a category of those who should have received genetic testing. Yet, she was not tested until after her cancer was found. From the limited facts we have, it appears that this timeline of events would have been outside accepted practice—and negligent. The case was not pursued by the patient, however, and this may represent the current state of liability for BRCA issues.
The extent of liability seems to be significant
Our discussion of liability suggests that there is significant potential for BRCA testing negligence within practice, and that the damages in these cases could be substantial. Yet the predicted “tsunami” of malpractice lawsuits related to genetic testing has not appeared.36,37 One study of cases in the United States (through 2016) found a “slowly rising tide” of liability cases instead of a tsunami,24 as the number of claims made was low. On the other hand, the payments where damages were awarded were an order of magnitude larger than other malpractice cases—a mean of $5.3 million and median of $2 million. This is compared with mean values in the range of $275,000 to $600,000 in other areas of malpractice.
The majority of the genetic malpractice cases involve prenatal and newborn testing, and diagnosis/susceptibility/pharmacogenomic accounting for about 25% of cases. In terms of type of errors claimed, approximately 50% were diagnostic-interpretation errors, 30% failure to offer testing, nearly 20% failure to return test results to the patients, and a few remaining cases of failure to properly treat in light of genetic testing.24
Despite a few very large payments, however, the fact remains that there is a surprisingly low number of genetics malpractice cases. Gary Marchant and colleagues suggest that several reasons may account for this:
- the clinical implementation of genetic science has been slower than expected
- the lack of expertise of many physicians in genetic science
- expert witnesses have sometimes been hard to find
- the lack of understanding by plaintiffs’ attorneys of genetic malpractice
- potential plaintiffs’ lack of understanding of the nature of genetic testing and the harms resulting from genetic negligence.17,24,37
The tide is slowly coming in
By all appearances, there is every reason to think that genetic malpractice will be increasing, and that the recent past of much higher damages per claim paid in the genetics area will be part of that tide. The National Human Genome Research LawSeq project has suggested a number of useful ways of dealing with the liability issues.18 In addition to the BRCA issues that we have considered in this article for ObGyns, there are other critical issues of prenatal and newborn genetic testing.38 But those are topics for another day. ●
- Sevilla C, Moatti JP, Reynier CJ, et al. Testing for BRCA1 mutations: a cost-effective analysis. Europ J Human Genetics. 2002;10:599-606.
- Cotton V, Kirkpatrick D. Failure to recommend genetic counseling in breast cancer: is the next wave of medical professional liability lawsuits? Contemp OB/GYN. June 1, 2017.
- Suryavanshi M, Kumar D, Panigrahi M, et al. Detection of false positive mutations in BRCA gene by next generation sequencing. Fam Cancer. 2017;16:311-317.
- Black L, Knoppers B, Avard D, et al. Legal liability and the uncertain nature of risk prediction: the case of breast cancer risk prediction models. Public Health Genomics. 2012;15:335-340.
- McClintock A, Gollab A, Laya M. Breast cancer risk assessment, a step-wise approach for primary care physicians on the front lines of shared decision making. Mayo Clin Proc. 2020;95:1268-1275.
- National Cancer Institute. The Breast Cancer Risk Assessment Tool. https://bcrisktool.cancer.gov/. Accessed February 25, 2021.
- Neff J, Richardson G, Phelps J. Legal liabilities associated with hereditary breast and ovarian cancers. J Reprod Med. 2020;65:227-230.
- American College of Obstetricians and Gynecologists. Practice Bulletin No 182: hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2017;130:e110-e126.
- Sá dos Reis C, Gremion I, and Meystre NR. Study of breast implants mammography examinations for identification of suitable image quality criteria. Insights Imaging. 2020;11:3.
- Association for Molecular Pathology v Myriad Genetics, 569 U.S. 576 (2013).
- Smith SR. The Supreme Court 2012-2013: dogs, DNA, and DOMA. Register Rep. 2013;39(Fall):26-33.
- Bal BS. An introduction to medical malpractice in the United States. Clin Orthop Relat Res. 2009;467:339-347.
- Helling v Carey, 83 Wn.2d 514, 519 P.2d 981 (1974).
- The T.J. Hooper, 60 F.2d 737, 740 (2d Cir.1932), cert. denied 287 U.S. 662 (1932).
- Fischer DA. Tort recovery for loss of a chance. Wake Forest L Rev. 2001;36:605-655.
- Murphy BL, Ray-Zack MD, Reddy PN, et al. Breast cancer litigation in the 21st century. Ann Surg Oncol. 2018;25:2939- 2947.
- Prince AE. Prevention for those who can pay: insurance reimbursement of genetic-based preventive interventions in the liminal state between health and disease. J Law Biosci. 2015;2:365-395.
- Marchant G, Barnes M, Evans JP, et al; LawSeq Liability Task Force. From genetics to genomics: facing the liability implications in clinical care. J Law Med Ethics. 2020;48:11-43.
- Complaint, Held v Ambry Genetics Corp., No. 15-CV-8683, 2015 WL 6750024 (S.D.N.Y. Nov. 4, 2015); Order of Dismissal, Held v Ambry Genetics Corp., No. 15-CV-8683, (S.D.N.Y. Dec. 6, 2016).
- Pederson HJ. Breast cancer risk assessment and treatment: current concepts in genetics and genomics. Contemp OB/ GYN. 2017; 62:A1-A4.
- Pederson HJ. Who needs breast cancer genetics testing? OBG Manag. 2018;30:34-39.
- Roberts JL, Foulkes A. Genetic duties. William Mary L Rev. 2020;62:143-212.
- Thorogood A, Cook-Deegan R, Knoppers B. Public variant databases: liability? Genet Med. 2017;19:838–841.
- Marchant G, Lindor R. Genomic malpractice: an emerging tide or gentle ripple? Food Drug Law J. 2018;73:1-37.
- National Human Genome Research Institute. Genetic discrimination. https://www.genome.gov/about-genomics /policy-issues/Genetic-Discrimination. Updated September 16, 2020. Accessed February 25, 2021.
- National Cancer Institute. BRCA mutations: cancer risk and genetic testing. https://www.cancer.gov/about-cancer /causes-prevention/genetics/brca-fact-sheet. Reviewed November 19, 2020. Accessed February 25, 2021.
- National Cancer Institute. Genetics of breast and gynecologic cancers (PDQ®)–Health Professional Version. https://www .cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq. Updated February 12, 2021. Accessed February 25, 2021.
- Reed v Campagnolo, 630 A.2d 1145, 1152–54 (Md. 1993).
- Munro v Regents of Univ. of Cal.,263 Cal. Rptr. 878, 885, 988 (1989).
- AMA Council on Ethical and Judicial Affairs. AMA Code of Medical Ethics’ opinions on genetic testing. Opinion 2.131. 2009;11:683-685. https://journalofethics.ama-assn .org/article/ama-code-medical-ethics-opinions-genetictesting/2009-09.
- Gilbar R, Barnoy S. Disclosing genetic test results to the patient’ relatives: how does the law influence clinical practice? J Law Technol Policy. 2019;125-168.
- Song K. Warning third parties of genetic risks in the era of personalized medicine. U.C. Davis L Rev. 2016;49:1987-2018.
- Tarasoff v Regents of the University of California, 551 P.2d 334, 131 Cal. Rptr. 14 (Cal. 1976).
- Safer v Estate of Pack, 677 A.2d 1188 (N.J. App. 1996), cert. denied, 683 A.2d 1163 (N.J. 1996).
- Pate v Threlkel, 661 So.2d 278 (Fla. 1995).
- Rothstein MA. Liability issues in pharmacogenomics. Louisiana L Rev. 2005;66:117-124.
- Marchant G, Lindor R. Personalized medicine and genetic malpractice. Genet Med. 2013;15:921-922.
- Westbrook M. Transforming the physician’s standard of care in the context of whole genome sequencing technologies: finding guidance in best practice standards. Saint Louis U J Health Law Policy. 2015;9:111-148.
Dr. Sanfilippo is Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, and Director, Reproductive Endocrinology and Infertility, at Magee-Womens Hospital, Pittsburgh, Pennsylvania. He also serves on the OBG Management Board of Editors.
Mr. Smith is Professor Emeritus and Dean Emeritus at California Western School of Law, San Diego, California.
The authors report no financial relationships relevant to this article.
Dr. Sanfilippo is Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, and Director, Reproductive Endocrinology and Infertility, at Magee-Womens Hospital, Pittsburgh, Pennsylvania. He also serves on the OBG Management Board of Editors.
Mr. Smith is Professor Emeritus and Dean Emeritus at California Western School of Law, San Diego, California.
The authors report no financial relationships relevant to this article.
Dr. Sanfilippo is Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, and Director, Reproductive Endocrinology and Infertility, at Magee-Womens Hospital, Pittsburgh, Pennsylvania. He also serves on the OBG Management Board of Editors.
Mr. Smith is Professor Emeritus and Dean Emeritus at California Western School of Law, San Diego, California.
The authors report no financial relationships relevant to this article.
CASE Young woman with family history of breast cancer detects lump
Two weeks after noting a lump on her breast when her cat happened to jump on her in that spot, a 28-year-old woman (G0) went to her primary care provider. She was referred to her gynecologist; breast imaging, ultrasonography, and mammography were obtained, with microcalcifications noted. A fine needle aspiration diagnosed intraductal malignancy. The surgical breast tissue specimen was estrogen receptor (ER)- and progestogen receptor (PR)-positive and HER2-negative. Other tumor markers were obtained, including carcinoembryonic antigen, and tissue polypeptide specific antigen, p53, cathepsin D, cyclin E, and nestin, but results were not available.
With regard to family history, the woman’s mother and maternal grandmother had a history of breast cancer. The patient and her family underwent gene testing. The patient was found to be BRCA1- and BRCA2-positive; her mother was BRCA1-positive, an older sister was BRCA2-positive, and her grandmother was not tested.
The question arose in light of her family history as to why she was not tested for BRCA and appropriately counseled by her gynecologist prior to the cancer diagnosis. Litigation was initiated. While the case did not go forward regarding litigation, it is indeed a case in point. (Please note that this is a hypothetical case. It is based on a composite of several cases.)
Medical considerations
Breast cancer is the most common type of cancer affecting women in the Western world.1 Advances in clinical testing for gene mutations have escalated and allowed for identification of patients at increased risk for breast and ovarian cancer. Along with these advances come professional liability risk. After looking at the medical considerations for BRCA1 and 2 testing, we will consider a number of important legal issues. In the view of some commentators, the failure to diagnose genetic mutations in patients predisposed to cancer is “poised to become the next wave of medical professional liability lawsuits.”2
BRCA1 and BRCA2 genes provide tumor suppressor proteins, and assessment for mutations is recommended for individuals at high risk for breast and/or ovarian cancer; mutations in BRCA genes cause DNA damage, which increases the chance of developing cancer. The other way to look at it is, BRCA1 and 2 are tumor suppressor genes that are integrally involved with DNA damage control. Once there is a mutation, it adversely affects the beneficial effects of the gene. Mutations in these genes account for 5% to 10% of all hereditary breast cancers.3 Of note, men with BRCA2 are at increased risk for prostate cancer.
A patient who presents to her gynecologist stating that there is a family history of breast cancer, without knowledge of genetic components, presents a challenge (and a medicolegal risk) for the provider to assess. Prediction models have been used to determine specific patient risk for carrying a genetic mutation with resultant breast cancer development.4 Risk prediction models do not appear to be a good answer to predicting who is more likely to develop breast or ovarian cancer, however. A Mayo model may assist (FIGURE).5 Clinicians should also be aware of other models of risk assessment, including the Gail Model (TABLE 1).6
Continue to: Guidelines for genetic testing...
Guidelines for genetic testing
The American College of Obstetricians and Gynecologists states that patient medical history and family history are paramount in obtaining information regarding risk for breast and ovarian cancer. First- and second-degree relatives are allocated to this category. Information regarding age of diagnosis, maternal and paternal lineage, and ethnic background can imply a need for genetic testing (TABLE 2).7,8 A number of genetics national organizations have participated in recommendations and include the American College of Medical Genetics and Genomics, the National Society for Genetic Counselors, and the Society of Gynecologic Oncology.7
The question always surfaces, could the clinical outcome of the cancer when diagnosed have been changed if screening were undertaken, with earlier diagnosis, or prevented with prophylactic mastectomy, and changed the end result. In addition, it is well known that breast augmentation mammoplasty alters the ability to accurately evaluate mammograms. Patients considering this type of plastic surgery, ideally, should be counselled accordingly.9
Bottom line, we as clinicians must be cognizant of both ACOG and United States Preventive Services Task Force (USPSTF) recommendations regarding screening and gene testing for women considered high risk for breast cancer based on family history.7
Legal considerations
The case presented demonstrates that the discovery of the BRCA1 and BRCA2 genes, and reliable tests for determining the existence of the genes, brought with them legal issues as well as medical advantages. We look at professional liability (malpractice) questions this technology raises, and then consider the outcome of the hypothetical case. (BRCA is used here to apply broadly—not only to BRCA1 and 2 but also to PALB2, CHEK2, and similar genetic abnormalities.)
To date, the most visible BRCA legal issues covered in cases and law reviews have focused more on patent law than malpractice. The most important of these was a decision of the US Supreme Court in Association for Molecular Pathology v Myriad Genetics.10 The US Patent Office was granting patents to companies finding useful, naturally occurring segments of human DNA, and had granted Myriad several patents on BRCA1 and BRCA2 genes. This patent policy had the potential to seriously interfere with broad scientific use of these genes.11 Fortunately, the Supreme Court stepped in and unanimously invalidated such patents. It held that a “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” The Court noted, “Finding the location of the BRCA1 and BRCA2 genes does not render the genes patent eligible ‘new . . . composition[s] of matter.’”8 The Court did allow the patenting of tests for specific gene structures, and artificial changes in naturally occurring genes.
Malpractice and BRCA
While the BRCA patent wars have lingered, the potential for a significant increase in BRCA-related malpractice cases is of increasing concern. Like most malpractice liability, these new claims are based on very old principles of negligence.12 To prevail, the plaintiff (ordinarily, an injured patient) must demonstrate 4 things:
- A duty. That is, the physician owed a duty to the injured party. Usually (but not always) that requires a professional relationship between the physician and the person injured.
- A breach of that duty. Malpractice liability is based on the fact that the physician did something that a reasonably careful physician (generally, of the same specialty) would not have done, or that the physician failed to do something that a reasonable physician would have done. This usually means that the profession itself sees what the physician did (or did not do) as medically inappropriate. In medical malpractice cases, that is ordinarily measured by what the usual or common practice is among prudent physicians. In rare circumstances, courts have found the standard practice of a profession to be negligent. Where, for example, it was custom for a professional not to give an eye pressure test to anyone under age 40, a court found that common standard to be inappropriate.13 In the words of Judge Learned Hand (speaking about a different case), “a whole calling may have unduly lagged in the adoption of new and available devices. It never may set its own tests.”14 Underlying negligence is a cost-benefit analysis (discussed below).
- Damages. There must have been some damage that courts recognize, usually loss of money or opportunity to work, the cost of care, pain and suffering, or loss of enjoyment/quality of life. In malpractice, many states now recognize the “loss of chance” or the “loss of a chance.” That means, if a “physician negligently fails to diagnose a curable disease, and the patient is harmed by the disease, the physician should be liable for causing the ‘loss of a chance of a cure.’”15 (Delay in diagnosis is the most common reason for claims in breast cancer care.)16
- Causation. The breach of duty (negligence) must have caused the damages. The causation must have been reasonably close. If a driver drives through a stop sign, or a physician misreads a test, and someone is injured but there is no connection between the negligence and the injury, there is not tort liability.
The 4 elements of malpractice just described are raised in some way in the possible liability associated with BRCA testing. We next look at the ways in which liability may arise from that testing (or lack of it).
Underlying much of the following discussion is the “cost-benefit” consideration noted above. This concept is that the total cost (financial and health) of testing should be compared with the value of the benefits of testing, taking into account the probabilities that the testing will result in better health outcomes. BRCA testing, for example, is essentially cost-free in terms of physical risk. Its financial cost, while not trivial, is not great, and it is commonly covered by health insurance.17 In terms of benefits, the testing has the potential for providing critical information in making treatment decisions for a meaningful percentage of patients and their families. There are many ways of analyzing the liability risks of genetic malpractice,7,18 and the following is intended to discuss some of the greatest risks related to BRCA testing.
Continue to: Areas of liability...
Areas of liability
The failure to recommend a test. The circumstances in which BRCA testing should be undertaken are set out by professional organizations (noted above). These recommendations are not static, however. They change from time to time. Given the potential harm caused by the failure to test in relevant circumstances, malpractice liability is certainly a possibility when the failure to recommend a test to a patient results in a cancer that might have been prevented had the genetic problem been identified in a timely manner. The circumstances in which testing should be considered continue to change, placing an obligation on clinicians to stay well informed of changing genetic understandings. Another risk is that one specialist may assume that it is the job of another specialist to order the test. Whatever the cause of the failure to test, or unnecessary delay in testing, it appears to be the primary basis for BRCA liability.
The failure to properly interpret a test. Any test that is misinterpreted may lead to harm for the patient. A false negative, of course, may mean that preventive treatment that could have been undertaken will be foregone, as a “loss of a chance.” On the other hand, a false positive can lead to radical, unnecessary surgery or treatment. If a misinterpretation occurred because of carelessness by the testing organization, or confusion by a practitioner, there is a likelihood of negligence.19
A different form of “misinterpretation” could be reasonable—and not negligent. Advances in scientific-medical understanding may result in the outcome of tests being reconsidered and changed. That has been the case with genetic testing and breast cancer. The availability of multiple breast cancer SNPs (single nucleotide polymorphisms), and combining this information with other risk factors for example, results in a polygenic risk score that may be at odds with the level of risk from earlier testing.20,21 This naturally leads to the question of when later, updated testing should be recommended to look for a better current interpretation.22,23
The failure to act on BRCA test results. Testing is of no value, of course, if the results are not used properly. Test results or analyses that are not sent to the proper physicians, or are somehow ignored when properly directed, is a “never” event—it should never happen. It almost always would be considered negligence, and if the patient were injured, could lead to liability. Amazingly, one study found that, in genetic testing liability cases, nearly 20% of the claims arose from failure to return test results to patients.24 In addition, when a patient is found to be BRCA-positive, there is an obligation to discuss the options for dealing with the increased risk associated with the gene mutation(s), as well as to recommend the prudent course of action or to refer the patient to someone who will have that discussion.
Informed consent to the patient. BRCA testing requires informed consent. The physical risks of the testing process are minimal, of course, but it carries a number of other emotional and family risks. The informed consent process is an invitation to an honest discussion between clinicians and patients. It should be an opportunity to discuss what the testing is, and is not, and what the test may mean for treatment. It may also be an opportunity to discuss the implications for other members of the patient’s family (noted below).
One element of informed consent is a discussion of the consequences of failure to consent, or to undertake one of the alternatives. In the case of BRCA testing, this is especially important in cases in which a patient expresses a hesitancy to be tested with an “I’d rather not know philosophy.” Although clinicians should not practice law, some patient concerns about discrimination may be addressed by the protection that the federal Genetic Information Nondiscrimination Act (GINA) and other laws provide (which prohibit insurance and employment discrimination based on genetic information). A good source of information about GINA and related nondiscrimination laws is provided by the National Human Genome Research Institute.25 In addition, the National Institutes of Health has a website that may be helpful to many patients26 (and a much more complex site for health professionals).27 At the same time, courts have resisted plaintiffs/patients who have tried to use informed consent as a way of suing for failure to offer genetic testing.28,29
The failure to refer. In some cases, a patient should be formally referred for genetics consultation. The considerations here are similar to other circumstances in modern, fast developing medical practice that require special sensitivity to those occasions in which a patient will benefit from additional expertise. It is a principle that the AMA Council on Ethical and Judicial Affairs has expressed this way: “In the absence of adequate expertise in pretest and posttest counseling, a physician should refer the patient to an appropriate specialist.”30 The failure to refer, when that deviates from acceptable practice, may result in liability.
Informing others. BRCA testing is an area of medicine in which results may be of great significance not only to the patient but also to the patient’s family.31 Physicians should counsel patients on the importance of informing relatives about relevant results and “should make themselves available to assist patients in communicating with relatives to discuss opportunities for counseling and testing, as appropriate.”30 The question may arise, however, of whether in some circumstances physicians should go a step further in ensuring relatives receive important information regarding their loved one’s health.32 The law has been reluctant to impose liability to “third parties” (someone not a patient). Duties usually arise through the physician-patient relationship. There are exceptions. Perhaps the best known has been the obligation of mental health professionals to take action to protect third parties from patients who have made believable threats against identifiable victims.33 There are indications that some courts could find, in extreme circumstances, a “duty to warn” nonpatients in some instances where it is essential to inform third parties that they should receive a specific form of genetic testing.34,35 Such a duty would, of course, have to protect the privacy rights of the patient to the maximum extent possible. A general duty of this type has not been established widely, but may be part of the future.
Continue to: Was there liability in our example case?...
Was there liability in our example case?
The hypothetical case provided above suggests that there could be liability. Routine medical history by the primary care physician would have produced the fact that the patient’s mother, sister, and maternal grandmother had breast cancer. That would clearly have put her in a category of those who should have received genetic testing. Yet, she was not tested until after her cancer was found. From the limited facts we have, it appears that this timeline of events would have been outside accepted practice—and negligent. The case was not pursued by the patient, however, and this may represent the current state of liability for BRCA issues.
The extent of liability seems to be significant
Our discussion of liability suggests that there is significant potential for BRCA testing negligence within practice, and that the damages in these cases could be substantial. Yet the predicted “tsunami” of malpractice lawsuits related to genetic testing has not appeared.36,37 One study of cases in the United States (through 2016) found a “slowly rising tide” of liability cases instead of a tsunami,24 as the number of claims made was low. On the other hand, the payments where damages were awarded were an order of magnitude larger than other malpractice cases—a mean of $5.3 million and median of $2 million. This is compared with mean values in the range of $275,000 to $600,000 in other areas of malpractice.
The majority of the genetic malpractice cases involve prenatal and newborn testing, and diagnosis/susceptibility/pharmacogenomic accounting for about 25% of cases. In terms of type of errors claimed, approximately 50% were diagnostic-interpretation errors, 30% failure to offer testing, nearly 20% failure to return test results to the patients, and a few remaining cases of failure to properly treat in light of genetic testing.24
Despite a few very large payments, however, the fact remains that there is a surprisingly low number of genetics malpractice cases. Gary Marchant and colleagues suggest that several reasons may account for this:
- the clinical implementation of genetic science has been slower than expected
- the lack of expertise of many physicians in genetic science
- expert witnesses have sometimes been hard to find
- the lack of understanding by plaintiffs’ attorneys of genetic malpractice
- potential plaintiffs’ lack of understanding of the nature of genetic testing and the harms resulting from genetic negligence.17,24,37
The tide is slowly coming in
By all appearances, there is every reason to think that genetic malpractice will be increasing, and that the recent past of much higher damages per claim paid in the genetics area will be part of that tide. The National Human Genome Research LawSeq project has suggested a number of useful ways of dealing with the liability issues.18 In addition to the BRCA issues that we have considered in this article for ObGyns, there are other critical issues of prenatal and newborn genetic testing.38 But those are topics for another day. ●
CASE Young woman with family history of breast cancer detects lump
Two weeks after noting a lump on her breast when her cat happened to jump on her in that spot, a 28-year-old woman (G0) went to her primary care provider. She was referred to her gynecologist; breast imaging, ultrasonography, and mammography were obtained, with microcalcifications noted. A fine needle aspiration diagnosed intraductal malignancy. The surgical breast tissue specimen was estrogen receptor (ER)- and progestogen receptor (PR)-positive and HER2-negative. Other tumor markers were obtained, including carcinoembryonic antigen, and tissue polypeptide specific antigen, p53, cathepsin D, cyclin E, and nestin, but results were not available.
With regard to family history, the woman’s mother and maternal grandmother had a history of breast cancer. The patient and her family underwent gene testing. The patient was found to be BRCA1- and BRCA2-positive; her mother was BRCA1-positive, an older sister was BRCA2-positive, and her grandmother was not tested.
The question arose in light of her family history as to why she was not tested for BRCA and appropriately counseled by her gynecologist prior to the cancer diagnosis. Litigation was initiated. While the case did not go forward regarding litigation, it is indeed a case in point. (Please note that this is a hypothetical case. It is based on a composite of several cases.)
Medical considerations
Breast cancer is the most common type of cancer affecting women in the Western world.1 Advances in clinical testing for gene mutations have escalated and allowed for identification of patients at increased risk for breast and ovarian cancer. Along with these advances come professional liability risk. After looking at the medical considerations for BRCA1 and 2 testing, we will consider a number of important legal issues. In the view of some commentators, the failure to diagnose genetic mutations in patients predisposed to cancer is “poised to become the next wave of medical professional liability lawsuits.”2
BRCA1 and BRCA2 genes provide tumor suppressor proteins, and assessment for mutations is recommended for individuals at high risk for breast and/or ovarian cancer; mutations in BRCA genes cause DNA damage, which increases the chance of developing cancer. The other way to look at it is, BRCA1 and 2 are tumor suppressor genes that are integrally involved with DNA damage control. Once there is a mutation, it adversely affects the beneficial effects of the gene. Mutations in these genes account for 5% to 10% of all hereditary breast cancers.3 Of note, men with BRCA2 are at increased risk for prostate cancer.
A patient who presents to her gynecologist stating that there is a family history of breast cancer, without knowledge of genetic components, presents a challenge (and a medicolegal risk) for the provider to assess. Prediction models have been used to determine specific patient risk for carrying a genetic mutation with resultant breast cancer development.4 Risk prediction models do not appear to be a good answer to predicting who is more likely to develop breast or ovarian cancer, however. A Mayo model may assist (FIGURE).5 Clinicians should also be aware of other models of risk assessment, including the Gail Model (TABLE 1).6
Continue to: Guidelines for genetic testing...
Guidelines for genetic testing
The American College of Obstetricians and Gynecologists states that patient medical history and family history are paramount in obtaining information regarding risk for breast and ovarian cancer. First- and second-degree relatives are allocated to this category. Information regarding age of diagnosis, maternal and paternal lineage, and ethnic background can imply a need for genetic testing (TABLE 2).7,8 A number of genetics national organizations have participated in recommendations and include the American College of Medical Genetics and Genomics, the National Society for Genetic Counselors, and the Society of Gynecologic Oncology.7
The question always surfaces, could the clinical outcome of the cancer when diagnosed have been changed if screening were undertaken, with earlier diagnosis, or prevented with prophylactic mastectomy, and changed the end result. In addition, it is well known that breast augmentation mammoplasty alters the ability to accurately evaluate mammograms. Patients considering this type of plastic surgery, ideally, should be counselled accordingly.9
Bottom line, we as clinicians must be cognizant of both ACOG and United States Preventive Services Task Force (USPSTF) recommendations regarding screening and gene testing for women considered high risk for breast cancer based on family history.7
Legal considerations
The case presented demonstrates that the discovery of the BRCA1 and BRCA2 genes, and reliable tests for determining the existence of the genes, brought with them legal issues as well as medical advantages. We look at professional liability (malpractice) questions this technology raises, and then consider the outcome of the hypothetical case. (BRCA is used here to apply broadly—not only to BRCA1 and 2 but also to PALB2, CHEK2, and similar genetic abnormalities.)
To date, the most visible BRCA legal issues covered in cases and law reviews have focused more on patent law than malpractice. The most important of these was a decision of the US Supreme Court in Association for Molecular Pathology v Myriad Genetics.10 The US Patent Office was granting patents to companies finding useful, naturally occurring segments of human DNA, and had granted Myriad several patents on BRCA1 and BRCA2 genes. This patent policy had the potential to seriously interfere with broad scientific use of these genes.11 Fortunately, the Supreme Court stepped in and unanimously invalidated such patents. It held that a “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” The Court noted, “Finding the location of the BRCA1 and BRCA2 genes does not render the genes patent eligible ‘new . . . composition[s] of matter.’”8 The Court did allow the patenting of tests for specific gene structures, and artificial changes in naturally occurring genes.
Malpractice and BRCA
While the BRCA patent wars have lingered, the potential for a significant increase in BRCA-related malpractice cases is of increasing concern. Like most malpractice liability, these new claims are based on very old principles of negligence.12 To prevail, the plaintiff (ordinarily, an injured patient) must demonstrate 4 things:
- A duty. That is, the physician owed a duty to the injured party. Usually (but not always) that requires a professional relationship between the physician and the person injured.
- A breach of that duty. Malpractice liability is based on the fact that the physician did something that a reasonably careful physician (generally, of the same specialty) would not have done, or that the physician failed to do something that a reasonable physician would have done. This usually means that the profession itself sees what the physician did (or did not do) as medically inappropriate. In medical malpractice cases, that is ordinarily measured by what the usual or common practice is among prudent physicians. In rare circumstances, courts have found the standard practice of a profession to be negligent. Where, for example, it was custom for a professional not to give an eye pressure test to anyone under age 40, a court found that common standard to be inappropriate.13 In the words of Judge Learned Hand (speaking about a different case), “a whole calling may have unduly lagged in the adoption of new and available devices. It never may set its own tests.”14 Underlying negligence is a cost-benefit analysis (discussed below).
- Damages. There must have been some damage that courts recognize, usually loss of money or opportunity to work, the cost of care, pain and suffering, or loss of enjoyment/quality of life. In malpractice, many states now recognize the “loss of chance” or the “loss of a chance.” That means, if a “physician negligently fails to diagnose a curable disease, and the patient is harmed by the disease, the physician should be liable for causing the ‘loss of a chance of a cure.’”15 (Delay in diagnosis is the most common reason for claims in breast cancer care.)16
- Causation. The breach of duty (negligence) must have caused the damages. The causation must have been reasonably close. If a driver drives through a stop sign, or a physician misreads a test, and someone is injured but there is no connection between the negligence and the injury, there is not tort liability.
The 4 elements of malpractice just described are raised in some way in the possible liability associated with BRCA testing. We next look at the ways in which liability may arise from that testing (or lack of it).
Underlying much of the following discussion is the “cost-benefit” consideration noted above. This concept is that the total cost (financial and health) of testing should be compared with the value of the benefits of testing, taking into account the probabilities that the testing will result in better health outcomes. BRCA testing, for example, is essentially cost-free in terms of physical risk. Its financial cost, while not trivial, is not great, and it is commonly covered by health insurance.17 In terms of benefits, the testing has the potential for providing critical information in making treatment decisions for a meaningful percentage of patients and their families. There are many ways of analyzing the liability risks of genetic malpractice,7,18 and the following is intended to discuss some of the greatest risks related to BRCA testing.
Continue to: Areas of liability...
Areas of liability
The failure to recommend a test. The circumstances in which BRCA testing should be undertaken are set out by professional organizations (noted above). These recommendations are not static, however. They change from time to time. Given the potential harm caused by the failure to test in relevant circumstances, malpractice liability is certainly a possibility when the failure to recommend a test to a patient results in a cancer that might have been prevented had the genetic problem been identified in a timely manner. The circumstances in which testing should be considered continue to change, placing an obligation on clinicians to stay well informed of changing genetic understandings. Another risk is that one specialist may assume that it is the job of another specialist to order the test. Whatever the cause of the failure to test, or unnecessary delay in testing, it appears to be the primary basis for BRCA liability.
The failure to properly interpret a test. Any test that is misinterpreted may lead to harm for the patient. A false negative, of course, may mean that preventive treatment that could have been undertaken will be foregone, as a “loss of a chance.” On the other hand, a false positive can lead to radical, unnecessary surgery or treatment. If a misinterpretation occurred because of carelessness by the testing organization, or confusion by a practitioner, there is a likelihood of negligence.19
A different form of “misinterpretation” could be reasonable—and not negligent. Advances in scientific-medical understanding may result in the outcome of tests being reconsidered and changed. That has been the case with genetic testing and breast cancer. The availability of multiple breast cancer SNPs (single nucleotide polymorphisms), and combining this information with other risk factors for example, results in a polygenic risk score that may be at odds with the level of risk from earlier testing.20,21 This naturally leads to the question of when later, updated testing should be recommended to look for a better current interpretation.22,23
The failure to act on BRCA test results. Testing is of no value, of course, if the results are not used properly. Test results or analyses that are not sent to the proper physicians, or are somehow ignored when properly directed, is a “never” event—it should never happen. It almost always would be considered negligence, and if the patient were injured, could lead to liability. Amazingly, one study found that, in genetic testing liability cases, nearly 20% of the claims arose from failure to return test results to patients.24 In addition, when a patient is found to be BRCA-positive, there is an obligation to discuss the options for dealing with the increased risk associated with the gene mutation(s), as well as to recommend the prudent course of action or to refer the patient to someone who will have that discussion.
Informed consent to the patient. BRCA testing requires informed consent. The physical risks of the testing process are minimal, of course, but it carries a number of other emotional and family risks. The informed consent process is an invitation to an honest discussion between clinicians and patients. It should be an opportunity to discuss what the testing is, and is not, and what the test may mean for treatment. It may also be an opportunity to discuss the implications for other members of the patient’s family (noted below).
One element of informed consent is a discussion of the consequences of failure to consent, or to undertake one of the alternatives. In the case of BRCA testing, this is especially important in cases in which a patient expresses a hesitancy to be tested with an “I’d rather not know philosophy.” Although clinicians should not practice law, some patient concerns about discrimination may be addressed by the protection that the federal Genetic Information Nondiscrimination Act (GINA) and other laws provide (which prohibit insurance and employment discrimination based on genetic information). A good source of information about GINA and related nondiscrimination laws is provided by the National Human Genome Research Institute.25 In addition, the National Institutes of Health has a website that may be helpful to many patients26 (and a much more complex site for health professionals).27 At the same time, courts have resisted plaintiffs/patients who have tried to use informed consent as a way of suing for failure to offer genetic testing.28,29
The failure to refer. In some cases, a patient should be formally referred for genetics consultation. The considerations here are similar to other circumstances in modern, fast developing medical practice that require special sensitivity to those occasions in which a patient will benefit from additional expertise. It is a principle that the AMA Council on Ethical and Judicial Affairs has expressed this way: “In the absence of adequate expertise in pretest and posttest counseling, a physician should refer the patient to an appropriate specialist.”30 The failure to refer, when that deviates from acceptable practice, may result in liability.
Informing others. BRCA testing is an area of medicine in which results may be of great significance not only to the patient but also to the patient’s family.31 Physicians should counsel patients on the importance of informing relatives about relevant results and “should make themselves available to assist patients in communicating with relatives to discuss opportunities for counseling and testing, as appropriate.”30 The question may arise, however, of whether in some circumstances physicians should go a step further in ensuring relatives receive important information regarding their loved one’s health.32 The law has been reluctant to impose liability to “third parties” (someone not a patient). Duties usually arise through the physician-patient relationship. There are exceptions. Perhaps the best known has been the obligation of mental health professionals to take action to protect third parties from patients who have made believable threats against identifiable victims.33 There are indications that some courts could find, in extreme circumstances, a “duty to warn” nonpatients in some instances where it is essential to inform third parties that they should receive a specific form of genetic testing.34,35 Such a duty would, of course, have to protect the privacy rights of the patient to the maximum extent possible. A general duty of this type has not been established widely, but may be part of the future.
Continue to: Was there liability in our example case?...
Was there liability in our example case?
The hypothetical case provided above suggests that there could be liability. Routine medical history by the primary care physician would have produced the fact that the patient’s mother, sister, and maternal grandmother had breast cancer. That would clearly have put her in a category of those who should have received genetic testing. Yet, she was not tested until after her cancer was found. From the limited facts we have, it appears that this timeline of events would have been outside accepted practice—and negligent. The case was not pursued by the patient, however, and this may represent the current state of liability for BRCA issues.
The extent of liability seems to be significant
Our discussion of liability suggests that there is significant potential for BRCA testing negligence within practice, and that the damages in these cases could be substantial. Yet the predicted “tsunami” of malpractice lawsuits related to genetic testing has not appeared.36,37 One study of cases in the United States (through 2016) found a “slowly rising tide” of liability cases instead of a tsunami,24 as the number of claims made was low. On the other hand, the payments where damages were awarded were an order of magnitude larger than other malpractice cases—a mean of $5.3 million and median of $2 million. This is compared with mean values in the range of $275,000 to $600,000 in other areas of malpractice.
The majority of the genetic malpractice cases involve prenatal and newborn testing, and diagnosis/susceptibility/pharmacogenomic accounting for about 25% of cases. In terms of type of errors claimed, approximately 50% were diagnostic-interpretation errors, 30% failure to offer testing, nearly 20% failure to return test results to the patients, and a few remaining cases of failure to properly treat in light of genetic testing.24
Despite a few very large payments, however, the fact remains that there is a surprisingly low number of genetics malpractice cases. Gary Marchant and colleagues suggest that several reasons may account for this:
- the clinical implementation of genetic science has been slower than expected
- the lack of expertise of many physicians in genetic science
- expert witnesses have sometimes been hard to find
- the lack of understanding by plaintiffs’ attorneys of genetic malpractice
- potential plaintiffs’ lack of understanding of the nature of genetic testing and the harms resulting from genetic negligence.17,24,37
The tide is slowly coming in
By all appearances, there is every reason to think that genetic malpractice will be increasing, and that the recent past of much higher damages per claim paid in the genetics area will be part of that tide. The National Human Genome Research LawSeq project has suggested a number of useful ways of dealing with the liability issues.18 In addition to the BRCA issues that we have considered in this article for ObGyns, there are other critical issues of prenatal and newborn genetic testing.38 But those are topics for another day. ●
- Sevilla C, Moatti JP, Reynier CJ, et al. Testing for BRCA1 mutations: a cost-effective analysis. Europ J Human Genetics. 2002;10:599-606.
- Cotton V, Kirkpatrick D. Failure to recommend genetic counseling in breast cancer: is the next wave of medical professional liability lawsuits? Contemp OB/GYN. June 1, 2017.
- Suryavanshi M, Kumar D, Panigrahi M, et al. Detection of false positive mutations in BRCA gene by next generation sequencing. Fam Cancer. 2017;16:311-317.
- Black L, Knoppers B, Avard D, et al. Legal liability and the uncertain nature of risk prediction: the case of breast cancer risk prediction models. Public Health Genomics. 2012;15:335-340.
- McClintock A, Gollab A, Laya M. Breast cancer risk assessment, a step-wise approach for primary care physicians on the front lines of shared decision making. Mayo Clin Proc. 2020;95:1268-1275.
- National Cancer Institute. The Breast Cancer Risk Assessment Tool. https://bcrisktool.cancer.gov/. Accessed February 25, 2021.
- Neff J, Richardson G, Phelps J. Legal liabilities associated with hereditary breast and ovarian cancers. J Reprod Med. 2020;65:227-230.
- American College of Obstetricians and Gynecologists. Practice Bulletin No 182: hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2017;130:e110-e126.
- Sá dos Reis C, Gremion I, and Meystre NR. Study of breast implants mammography examinations for identification of suitable image quality criteria. Insights Imaging. 2020;11:3.
- Association for Molecular Pathology v Myriad Genetics, 569 U.S. 576 (2013).
- Smith SR. The Supreme Court 2012-2013: dogs, DNA, and DOMA. Register Rep. 2013;39(Fall):26-33.
- Bal BS. An introduction to medical malpractice in the United States. Clin Orthop Relat Res. 2009;467:339-347.
- Helling v Carey, 83 Wn.2d 514, 519 P.2d 981 (1974).
- The T.J. Hooper, 60 F.2d 737, 740 (2d Cir.1932), cert. denied 287 U.S. 662 (1932).
- Fischer DA. Tort recovery for loss of a chance. Wake Forest L Rev. 2001;36:605-655.
- Murphy BL, Ray-Zack MD, Reddy PN, et al. Breast cancer litigation in the 21st century. Ann Surg Oncol. 2018;25:2939- 2947.
- Prince AE. Prevention for those who can pay: insurance reimbursement of genetic-based preventive interventions in the liminal state between health and disease. J Law Biosci. 2015;2:365-395.
- Marchant G, Barnes M, Evans JP, et al; LawSeq Liability Task Force. From genetics to genomics: facing the liability implications in clinical care. J Law Med Ethics. 2020;48:11-43.
- Complaint, Held v Ambry Genetics Corp., No. 15-CV-8683, 2015 WL 6750024 (S.D.N.Y. Nov. 4, 2015); Order of Dismissal, Held v Ambry Genetics Corp., No. 15-CV-8683, (S.D.N.Y. Dec. 6, 2016).
- Pederson HJ. Breast cancer risk assessment and treatment: current concepts in genetics and genomics. Contemp OB/ GYN. 2017; 62:A1-A4.
- Pederson HJ. Who needs breast cancer genetics testing? OBG Manag. 2018;30:34-39.
- Roberts JL, Foulkes A. Genetic duties. William Mary L Rev. 2020;62:143-212.
- Thorogood A, Cook-Deegan R, Knoppers B. Public variant databases: liability? Genet Med. 2017;19:838–841.
- Marchant G, Lindor R. Genomic malpractice: an emerging tide or gentle ripple? Food Drug Law J. 2018;73:1-37.
- National Human Genome Research Institute. Genetic discrimination. https://www.genome.gov/about-genomics /policy-issues/Genetic-Discrimination. Updated September 16, 2020. Accessed February 25, 2021.
- National Cancer Institute. BRCA mutations: cancer risk and genetic testing. https://www.cancer.gov/about-cancer /causes-prevention/genetics/brca-fact-sheet. Reviewed November 19, 2020. Accessed February 25, 2021.
- National Cancer Institute. Genetics of breast and gynecologic cancers (PDQ®)–Health Professional Version. https://www .cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq. Updated February 12, 2021. Accessed February 25, 2021.
- Reed v Campagnolo, 630 A.2d 1145, 1152–54 (Md. 1993).
- Munro v Regents of Univ. of Cal.,263 Cal. Rptr. 878, 885, 988 (1989).
- AMA Council on Ethical and Judicial Affairs. AMA Code of Medical Ethics’ opinions on genetic testing. Opinion 2.131. 2009;11:683-685. https://journalofethics.ama-assn .org/article/ama-code-medical-ethics-opinions-genetictesting/2009-09.
- Gilbar R, Barnoy S. Disclosing genetic test results to the patient’ relatives: how does the law influence clinical practice? J Law Technol Policy. 2019;125-168.
- Song K. Warning third parties of genetic risks in the era of personalized medicine. U.C. Davis L Rev. 2016;49:1987-2018.
- Tarasoff v Regents of the University of California, 551 P.2d 334, 131 Cal. Rptr. 14 (Cal. 1976).
- Safer v Estate of Pack, 677 A.2d 1188 (N.J. App. 1996), cert. denied, 683 A.2d 1163 (N.J. 1996).
- Pate v Threlkel, 661 So.2d 278 (Fla. 1995).
- Rothstein MA. Liability issues in pharmacogenomics. Louisiana L Rev. 2005;66:117-124.
- Marchant G, Lindor R. Personalized medicine and genetic malpractice. Genet Med. 2013;15:921-922.
- Westbrook M. Transforming the physician’s standard of care in the context of whole genome sequencing technologies: finding guidance in best practice standards. Saint Louis U J Health Law Policy. 2015;9:111-148.
- Sevilla C, Moatti JP, Reynier CJ, et al. Testing for BRCA1 mutations: a cost-effective analysis. Europ J Human Genetics. 2002;10:599-606.
- Cotton V, Kirkpatrick D. Failure to recommend genetic counseling in breast cancer: is the next wave of medical professional liability lawsuits? Contemp OB/GYN. June 1, 2017.
- Suryavanshi M, Kumar D, Panigrahi M, et al. Detection of false positive mutations in BRCA gene by next generation sequencing. Fam Cancer. 2017;16:311-317.
- Black L, Knoppers B, Avard D, et al. Legal liability and the uncertain nature of risk prediction: the case of breast cancer risk prediction models. Public Health Genomics. 2012;15:335-340.
- McClintock A, Gollab A, Laya M. Breast cancer risk assessment, a step-wise approach for primary care physicians on the front lines of shared decision making. Mayo Clin Proc. 2020;95:1268-1275.
- National Cancer Institute. The Breast Cancer Risk Assessment Tool. https://bcrisktool.cancer.gov/. Accessed February 25, 2021.
- Neff J, Richardson G, Phelps J. Legal liabilities associated with hereditary breast and ovarian cancers. J Reprod Med. 2020;65:227-230.
- American College of Obstetricians and Gynecologists. Practice Bulletin No 182: hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2017;130:e110-e126.
- Sá dos Reis C, Gremion I, and Meystre NR. Study of breast implants mammography examinations for identification of suitable image quality criteria. Insights Imaging. 2020;11:3.
- Association for Molecular Pathology v Myriad Genetics, 569 U.S. 576 (2013).
- Smith SR. The Supreme Court 2012-2013: dogs, DNA, and DOMA. Register Rep. 2013;39(Fall):26-33.
- Bal BS. An introduction to medical malpractice in the United States. Clin Orthop Relat Res. 2009;467:339-347.
- Helling v Carey, 83 Wn.2d 514, 519 P.2d 981 (1974).
- The T.J. Hooper, 60 F.2d 737, 740 (2d Cir.1932), cert. denied 287 U.S. 662 (1932).
- Fischer DA. Tort recovery for loss of a chance. Wake Forest L Rev. 2001;36:605-655.
- Murphy BL, Ray-Zack MD, Reddy PN, et al. Breast cancer litigation in the 21st century. Ann Surg Oncol. 2018;25:2939- 2947.
- Prince AE. Prevention for those who can pay: insurance reimbursement of genetic-based preventive interventions in the liminal state between health and disease. J Law Biosci. 2015;2:365-395.
- Marchant G, Barnes M, Evans JP, et al; LawSeq Liability Task Force. From genetics to genomics: facing the liability implications in clinical care. J Law Med Ethics. 2020;48:11-43.
- Complaint, Held v Ambry Genetics Corp., No. 15-CV-8683, 2015 WL 6750024 (S.D.N.Y. Nov. 4, 2015); Order of Dismissal, Held v Ambry Genetics Corp., No. 15-CV-8683, (S.D.N.Y. Dec. 6, 2016).
- Pederson HJ. Breast cancer risk assessment and treatment: current concepts in genetics and genomics. Contemp OB/ GYN. 2017; 62:A1-A4.
- Pederson HJ. Who needs breast cancer genetics testing? OBG Manag. 2018;30:34-39.
- Roberts JL, Foulkes A. Genetic duties. William Mary L Rev. 2020;62:143-212.
- Thorogood A, Cook-Deegan R, Knoppers B. Public variant databases: liability? Genet Med. 2017;19:838–841.
- Marchant G, Lindor R. Genomic malpractice: an emerging tide or gentle ripple? Food Drug Law J. 2018;73:1-37.
- National Human Genome Research Institute. Genetic discrimination. https://www.genome.gov/about-genomics /policy-issues/Genetic-Discrimination. Updated September 16, 2020. Accessed February 25, 2021.
- National Cancer Institute. BRCA mutations: cancer risk and genetic testing. https://www.cancer.gov/about-cancer /causes-prevention/genetics/brca-fact-sheet. Reviewed November 19, 2020. Accessed February 25, 2021.
- National Cancer Institute. Genetics of breast and gynecologic cancers (PDQ®)–Health Professional Version. https://www .cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq. Updated February 12, 2021. Accessed February 25, 2021.
- Reed v Campagnolo, 630 A.2d 1145, 1152–54 (Md. 1993).
- Munro v Regents of Univ. of Cal.,263 Cal. Rptr. 878, 885, 988 (1989).
- AMA Council on Ethical and Judicial Affairs. AMA Code of Medical Ethics’ opinions on genetic testing. Opinion 2.131. 2009;11:683-685. https://journalofethics.ama-assn .org/article/ama-code-medical-ethics-opinions-genetictesting/2009-09.
- Gilbar R, Barnoy S. Disclosing genetic test results to the patient’ relatives: how does the law influence clinical practice? J Law Technol Policy. 2019;125-168.
- Song K. Warning third parties of genetic risks in the era of personalized medicine. U.C. Davis L Rev. 2016;49:1987-2018.
- Tarasoff v Regents of the University of California, 551 P.2d 334, 131 Cal. Rptr. 14 (Cal. 1976).
- Safer v Estate of Pack, 677 A.2d 1188 (N.J. App. 1996), cert. denied, 683 A.2d 1163 (N.J. 1996).
- Pate v Threlkel, 661 So.2d 278 (Fla. 1995).
- Rothstein MA. Liability issues in pharmacogenomics. Louisiana L Rev. 2005;66:117-124.
- Marchant G, Lindor R. Personalized medicine and genetic malpractice. Genet Med. 2013;15:921-922.
- Westbrook M. Transforming the physician’s standard of care in the context of whole genome sequencing technologies: finding guidance in best practice standards. Saint Louis U J Health Law Policy. 2015;9:111-148.
Palliative care for patients with dementia: When to refer?
Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer,
A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.
For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
Standardized criteria is lacking
The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.
A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.
Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.
Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.
The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.
Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.
Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
A starting point for further discussion
Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.
“Sometimes you need a paper like this to kick off the discussion to say look, this is where we are,” Dr. Sampson said, noting that the focus on need-based criteria dovetailed with a “general feeling in the field that we need to really think about needs, and what palliative care needs might be. What the threshold for referral should be we don’t know yet. Should it be three unmet needs? Or five? We’re still a long way from knowing.”
Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.
One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”
Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.
Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer,
A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.
For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
Standardized criteria is lacking
The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.
A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.
Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.
Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.
The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.
Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.
Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
A starting point for further discussion
Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.
“Sometimes you need a paper like this to kick off the discussion to say look, this is where we are,” Dr. Sampson said, noting that the focus on need-based criteria dovetailed with a “general feeling in the field that we need to really think about needs, and what palliative care needs might be. What the threshold for referral should be we don’t know yet. Should it be three unmet needs? Or five? We’re still a long way from knowing.”
Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.
One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”
Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.
Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer,
A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.
For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
Standardized criteria is lacking
The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.
A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.
Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.
Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.
The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.
Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.
Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
A starting point for further discussion
Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.
“Sometimes you need a paper like this to kick off the discussion to say look, this is where we are,” Dr. Sampson said, noting that the focus on need-based criteria dovetailed with a “general feeling in the field that we need to really think about needs, and what palliative care needs might be. What the threshold for referral should be we don’t know yet. Should it be three unmet needs? Or five? We’re still a long way from knowing.”
Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.
One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”
Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.
FROM THE JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
Clinical Edge Journal Scan Commentary: Breast Cancer March 2021
Peripheral neuropathy is a well-recognized complication of taxane therapy that can impact functioning and quality of life. Dose-reductions are applied in an effort to continue treatment and minimize risk of worsening neuropathy. In a prospective analysis of breast cancer patients receiving weekly paclitaxel, Timmins et al showed neuropathy symptoms affected 85% with severe symptoms in 38%, and about half of the cohort had persistent symptoms up to 12 months post-chemotherapy. Patients who received dose reductions reported worse neuropathy and symptom burden compared to those who received full dose paclitaxel chemotherapy. It is challenging to predict with certainty which patients may experience significant neuropathy, and important to acknowledge individual patients factors such as age and other medical co-morbidities. Additional research is warranted to refine individual risk assessment as well as prevention and management strategies.
The treatment landscape for metastatic HER2-positive breast cancer is evolving at a rapid pace. Margetuximab is a chimeric antibody with similar epitope specificity to trastuzumab, but with an engineered Fc region that enhances immune activation. The phase 3 SOPHIA trial included 536 patients with pretreated HER2-positive advanced breast cancer and demonstrated modest improvement in progression free-survival with margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy (median PFS 5.8 versus 4.9 months; HR 0.76, p=0.03). The introduction of other therapies in this space (tucatinib, trastuzumab deruxtecan, neratinib) provides patients with many options, but simultaneously creates a complex treatment algorithm when it comes to therapy selection. Toxicity profiles and sites of metastases should be taken into consideration when deciding on best therapy for an individual patient.
Given the impressive outcomes seen with endocrine therapy plus CDK 4/6 inhibitors in the advanced HR+/HER2- population, these combinations are being studied in the curative setting. The phase 3 PALLAS study randomized 5,760 patients with stage I-III HR+/HER2- breast cancer to ongoing endocrine therapy with or without palbociclib for 2 years. Data from the second interim analysis of this trial showed similar invasive disease-free survival rates for the two arms (3 years iDFS 88.2% for palbociclib plus endocrine therapy versus 88.5% for endocrine therapy alone; HR 0.93, p=0.51). In contrast, the phase 3 monarchE trial showed improvement in iDFS with abemaciclib for 2 years with ongoing endocrine therapy compared to endocrine therapy alone (2 year iDFS rate of 92.3% versus 89.3%; HR 0.713, p=0.0009). Differences in study populations, mechanism of action of various CDK 4/6 inhibitors, dosing and drug exposure, may possibly impact results. Long-term follow-up and biomarker studies are desired to further delineate the role of CDK 4/6 inhibitors in this setting.
References:
Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34:611-35.
Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018;18:958.
O'Shaughnessy JA, Johnston S, Harbeck N, Toi M, Im Y-H, Reinisch M, Shao Z, Kellokumpu Lehtinen PL, Huang C-S, Tryakin A, Goetz M, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Steger GG, Del Mastro L, Cox J, Forrester T, Sherwood S, Li X, Wei R, Martin M, Rastogi P. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract GS1-01.
Peripheral neuropathy is a well-recognized complication of taxane therapy that can impact functioning and quality of life. Dose-reductions are applied in an effort to continue treatment and minimize risk of worsening neuropathy. In a prospective analysis of breast cancer patients receiving weekly paclitaxel, Timmins et al showed neuropathy symptoms affected 85% with severe symptoms in 38%, and about half of the cohort had persistent symptoms up to 12 months post-chemotherapy. Patients who received dose reductions reported worse neuropathy and symptom burden compared to those who received full dose paclitaxel chemotherapy. It is challenging to predict with certainty which patients may experience significant neuropathy, and important to acknowledge individual patients factors such as age and other medical co-morbidities. Additional research is warranted to refine individual risk assessment as well as prevention and management strategies.
The treatment landscape for metastatic HER2-positive breast cancer is evolving at a rapid pace. Margetuximab is a chimeric antibody with similar epitope specificity to trastuzumab, but with an engineered Fc region that enhances immune activation. The phase 3 SOPHIA trial included 536 patients with pretreated HER2-positive advanced breast cancer and demonstrated modest improvement in progression free-survival with margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy (median PFS 5.8 versus 4.9 months; HR 0.76, p=0.03). The introduction of other therapies in this space (tucatinib, trastuzumab deruxtecan, neratinib) provides patients with many options, but simultaneously creates a complex treatment algorithm when it comes to therapy selection. Toxicity profiles and sites of metastases should be taken into consideration when deciding on best therapy for an individual patient.
Given the impressive outcomes seen with endocrine therapy plus CDK 4/6 inhibitors in the advanced HR+/HER2- population, these combinations are being studied in the curative setting. The phase 3 PALLAS study randomized 5,760 patients with stage I-III HR+/HER2- breast cancer to ongoing endocrine therapy with or without palbociclib for 2 years. Data from the second interim analysis of this trial showed similar invasive disease-free survival rates for the two arms (3 years iDFS 88.2% for palbociclib plus endocrine therapy versus 88.5% for endocrine therapy alone; HR 0.93, p=0.51). In contrast, the phase 3 monarchE trial showed improvement in iDFS with abemaciclib for 2 years with ongoing endocrine therapy compared to endocrine therapy alone (2 year iDFS rate of 92.3% versus 89.3%; HR 0.713, p=0.0009). Differences in study populations, mechanism of action of various CDK 4/6 inhibitors, dosing and drug exposure, may possibly impact results. Long-term follow-up and biomarker studies are desired to further delineate the role of CDK 4/6 inhibitors in this setting.
References:
Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34:611-35.
Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018;18:958.
O'Shaughnessy JA, Johnston S, Harbeck N, Toi M, Im Y-H, Reinisch M, Shao Z, Kellokumpu Lehtinen PL, Huang C-S, Tryakin A, Goetz M, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Steger GG, Del Mastro L, Cox J, Forrester T, Sherwood S, Li X, Wei R, Martin M, Rastogi P. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract GS1-01.
Peripheral neuropathy is a well-recognized complication of taxane therapy that can impact functioning and quality of life. Dose-reductions are applied in an effort to continue treatment and minimize risk of worsening neuropathy. In a prospective analysis of breast cancer patients receiving weekly paclitaxel, Timmins et al showed neuropathy symptoms affected 85% with severe symptoms in 38%, and about half of the cohort had persistent symptoms up to 12 months post-chemotherapy. Patients who received dose reductions reported worse neuropathy and symptom burden compared to those who received full dose paclitaxel chemotherapy. It is challenging to predict with certainty which patients may experience significant neuropathy, and important to acknowledge individual patients factors such as age and other medical co-morbidities. Additional research is warranted to refine individual risk assessment as well as prevention and management strategies.
The treatment landscape for metastatic HER2-positive breast cancer is evolving at a rapid pace. Margetuximab is a chimeric antibody with similar epitope specificity to trastuzumab, but with an engineered Fc region that enhances immune activation. The phase 3 SOPHIA trial included 536 patients with pretreated HER2-positive advanced breast cancer and demonstrated modest improvement in progression free-survival with margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy (median PFS 5.8 versus 4.9 months; HR 0.76, p=0.03). The introduction of other therapies in this space (tucatinib, trastuzumab deruxtecan, neratinib) provides patients with many options, but simultaneously creates a complex treatment algorithm when it comes to therapy selection. Toxicity profiles and sites of metastases should be taken into consideration when deciding on best therapy for an individual patient.
Given the impressive outcomes seen with endocrine therapy plus CDK 4/6 inhibitors in the advanced HR+/HER2- population, these combinations are being studied in the curative setting. The phase 3 PALLAS study randomized 5,760 patients with stage I-III HR+/HER2- breast cancer to ongoing endocrine therapy with or without palbociclib for 2 years. Data from the second interim analysis of this trial showed similar invasive disease-free survival rates for the two arms (3 years iDFS 88.2% for palbociclib plus endocrine therapy versus 88.5% for endocrine therapy alone; HR 0.93, p=0.51). In contrast, the phase 3 monarchE trial showed improvement in iDFS with abemaciclib for 2 years with ongoing endocrine therapy compared to endocrine therapy alone (2 year iDFS rate of 92.3% versus 89.3%; HR 0.713, p=0.0009). Differences in study populations, mechanism of action of various CDK 4/6 inhibitors, dosing and drug exposure, may possibly impact results. Long-term follow-up and biomarker studies are desired to further delineate the role of CDK 4/6 inhibitors in this setting.
References:
Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34:611-35.
Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018;18:958.
O'Shaughnessy JA, Johnston S, Harbeck N, Toi M, Im Y-H, Reinisch M, Shao Z, Kellokumpu Lehtinen PL, Huang C-S, Tryakin A, Goetz M, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Steger GG, Del Mastro L, Cox J, Forrester T, Sherwood S, Li X, Wei R, Martin M, Rastogi P. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract GS1-01.
De-escalated radiation and endocrine therapy strategies in older women with breast cancer
Key clinical point: Adjuvant radiation therapy (RT) alone or in combination with endocrine therapy (ET) was associated with a lower risk for recurrence than ET alone in older women with early node-negative, human receptor-positive (HR+) breast cancer (BC). In addition, most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors.
Major finding: Compared with ET alone, use of RT+ET (hazard ratio [HR], 0.62; P less than .0001) and RT alone (HR, 0.75; P less than .0001) was associated with a lower risk for recurrence at a median follow-up of 48 months. RT was received by 65.5% of patients, with no decrease over time. However, patients with T2 vs. T1 tumors remained less likely to receive RT (odds ratio, 0.83; P = .0024).
Study details: This study evaluated the use of adjuvant RT (n=2,046), ET (n=2,407), or RT+ET (n=4,643) after breast-conserving therapeutic surgery in older women (age at diagnosis, 66 years or more) with T1-2 node-negative, HR+ BC.
Disclosures: This study was supported by grants from the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, and the American Society for Radiation Oncology. Some of the study investigators reported employment and ownership in various pharmaceutical companies.
Source: Reeder-Hayes KE et al. J Geriatr Oncol. 2021 Feb 4. doi: 10.1016/j.jgo.2021.01.003.
Key clinical point: Adjuvant radiation therapy (RT) alone or in combination with endocrine therapy (ET) was associated with a lower risk for recurrence than ET alone in older women with early node-negative, human receptor-positive (HR+) breast cancer (BC). In addition, most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors.
Major finding: Compared with ET alone, use of RT+ET (hazard ratio [HR], 0.62; P less than .0001) and RT alone (HR, 0.75; P less than .0001) was associated with a lower risk for recurrence at a median follow-up of 48 months. RT was received by 65.5% of patients, with no decrease over time. However, patients with T2 vs. T1 tumors remained less likely to receive RT (odds ratio, 0.83; P = .0024).
Study details: This study evaluated the use of adjuvant RT (n=2,046), ET (n=2,407), or RT+ET (n=4,643) after breast-conserving therapeutic surgery in older women (age at diagnosis, 66 years or more) with T1-2 node-negative, HR+ BC.
Disclosures: This study was supported by grants from the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, and the American Society for Radiation Oncology. Some of the study investigators reported employment and ownership in various pharmaceutical companies.
Source: Reeder-Hayes KE et al. J Geriatr Oncol. 2021 Feb 4. doi: 10.1016/j.jgo.2021.01.003.
Key clinical point: Adjuvant radiation therapy (RT) alone or in combination with endocrine therapy (ET) was associated with a lower risk for recurrence than ET alone in older women with early node-negative, human receptor-positive (HR+) breast cancer (BC). In addition, most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors.
Major finding: Compared with ET alone, use of RT+ET (hazard ratio [HR], 0.62; P less than .0001) and RT alone (HR, 0.75; P less than .0001) was associated with a lower risk for recurrence at a median follow-up of 48 months. RT was received by 65.5% of patients, with no decrease over time. However, patients with T2 vs. T1 tumors remained less likely to receive RT (odds ratio, 0.83; P = .0024).
Study details: This study evaluated the use of adjuvant RT (n=2,046), ET (n=2,407), or RT+ET (n=4,643) after breast-conserving therapeutic surgery in older women (age at diagnosis, 66 years or more) with T1-2 node-negative, HR+ BC.
Disclosures: This study was supported by grants from the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, and the American Society for Radiation Oncology. Some of the study investigators reported employment and ownership in various pharmaceutical companies.
Source: Reeder-Hayes KE et al. J Geriatr Oncol. 2021 Feb 4. doi: 10.1016/j.jgo.2021.01.003.
Locoregional surgery improves PFS in de novo stage IV breast cancer
Key clinical point: Locoregional surgery of the primary tumor vs. no surgery significantly improved locoregional progression-free survival (PFS) in patients with de novo stage IV breast cancer.
Major finding: Locoregional PFS was significantly longer with locoregional surgery vs. no surgery (hazard ratio, 0.23; P less than .001).
Study details: Findings are from a meta-analysis of 1,110 patients from 6 prospective clinical trials and 353 patients from a cohort study that assessed effects of locoregional surgery vs. no surgery in de novo stage IV breast cancer.
Disclosures: This study was supported by grants from the National Science and Technology Major Project, Sun Yat-Sen Memorial Hospital, the National Natural Science Foundation of Guangdong Province, Guangzhou Science and Technology Major Program, the Guangdong Science and Technology Department, Sun Yat-Sen University Clinical Research 5010 Program, and Sun Yat-Sen Clinical Research Cultivating Program. The authors declared no conflicts of interest.
Source: Yu Y et al. Ann Surg Oncol. 2021 Feb 3. doi: 10.1245/s10434-021-09650-3.
Key clinical point: Locoregional surgery of the primary tumor vs. no surgery significantly improved locoregional progression-free survival (PFS) in patients with de novo stage IV breast cancer.
Major finding: Locoregional PFS was significantly longer with locoregional surgery vs. no surgery (hazard ratio, 0.23; P less than .001).
Study details: Findings are from a meta-analysis of 1,110 patients from 6 prospective clinical trials and 353 patients from a cohort study that assessed effects of locoregional surgery vs. no surgery in de novo stage IV breast cancer.
Disclosures: This study was supported by grants from the National Science and Technology Major Project, Sun Yat-Sen Memorial Hospital, the National Natural Science Foundation of Guangdong Province, Guangzhou Science and Technology Major Program, the Guangdong Science and Technology Department, Sun Yat-Sen University Clinical Research 5010 Program, and Sun Yat-Sen Clinical Research Cultivating Program. The authors declared no conflicts of interest.
Source: Yu Y et al. Ann Surg Oncol. 2021 Feb 3. doi: 10.1245/s10434-021-09650-3.
Key clinical point: Locoregional surgery of the primary tumor vs. no surgery significantly improved locoregional progression-free survival (PFS) in patients with de novo stage IV breast cancer.
Major finding: Locoregional PFS was significantly longer with locoregional surgery vs. no surgery (hazard ratio, 0.23; P less than .001).
Study details: Findings are from a meta-analysis of 1,110 patients from 6 prospective clinical trials and 353 patients from a cohort study that assessed effects of locoregional surgery vs. no surgery in de novo stage IV breast cancer.
Disclosures: This study was supported by grants from the National Science and Technology Major Project, Sun Yat-Sen Memorial Hospital, the National Natural Science Foundation of Guangdong Province, Guangzhou Science and Technology Major Program, the Guangdong Science and Technology Department, Sun Yat-Sen University Clinical Research 5010 Program, and Sun Yat-Sen Clinical Research Cultivating Program. The authors declared no conflicts of interest.
Source: Yu Y et al. Ann Surg Oncol. 2021 Feb 3. doi: 10.1245/s10434-021-09650-3.
Early breast cancer: Rates of local recurrence higher with APBI than WBI
Key clinical point: Rates of local recurrence were higher with accelerated partial breast irradiation (APBI) than whole breast irradiation (WBI) in patients receiving breast-conservation treatment for early-stage breast cancer. Rate of distant metastasis, overall survival (OS), and disease-free survival (DFS) were similar.
Major finding: Patients receiving APBI vs. WBI had significantly higher rates of local recurrence (hazard ratio [HR], 1.46; P = .0002). DFS (HR, 1.11; P = .09), OS (HR, 1.11; P = .09), and distant metastasis (HR, 1.17; P = .11) were not different between the groups.
Study details: Findings are from a meta-analysis of 10 randomized controlled trials including 15,500 patients with early-stage breast cancer, including 7,758 patients in APBI and 7,742 patients in WBI groups.
Disclosures: No funding source was identified. The authors declared no conflicts of interest.
Source: Xiang X et al. Radiat Oncol. 2021 Feb 2. doi: 10.1186/s13014-021-01752-2.
Key clinical point: Rates of local recurrence were higher with accelerated partial breast irradiation (APBI) than whole breast irradiation (WBI) in patients receiving breast-conservation treatment for early-stage breast cancer. Rate of distant metastasis, overall survival (OS), and disease-free survival (DFS) were similar.
Major finding: Patients receiving APBI vs. WBI had significantly higher rates of local recurrence (hazard ratio [HR], 1.46; P = .0002). DFS (HR, 1.11; P = .09), OS (HR, 1.11; P = .09), and distant metastasis (HR, 1.17; P = .11) were not different between the groups.
Study details: Findings are from a meta-analysis of 10 randomized controlled trials including 15,500 patients with early-stage breast cancer, including 7,758 patients in APBI and 7,742 patients in WBI groups.
Disclosures: No funding source was identified. The authors declared no conflicts of interest.
Source: Xiang X et al. Radiat Oncol. 2021 Feb 2. doi: 10.1186/s13014-021-01752-2.
Key clinical point: Rates of local recurrence were higher with accelerated partial breast irradiation (APBI) than whole breast irradiation (WBI) in patients receiving breast-conservation treatment for early-stage breast cancer. Rate of distant metastasis, overall survival (OS), and disease-free survival (DFS) were similar.
Major finding: Patients receiving APBI vs. WBI had significantly higher rates of local recurrence (hazard ratio [HR], 1.46; P = .0002). DFS (HR, 1.11; P = .09), OS (HR, 1.11; P = .09), and distant metastasis (HR, 1.17; P = .11) were not different between the groups.
Study details: Findings are from a meta-analysis of 10 randomized controlled trials including 15,500 patients with early-stage breast cancer, including 7,758 patients in APBI and 7,742 patients in WBI groups.
Disclosures: No funding source was identified. The authors declared no conflicts of interest.
Source: Xiang X et al. Radiat Oncol. 2021 Feb 2. doi: 10.1186/s13014-021-01752-2.
HR+ early breast cancer: Palbociclib + adjuvant ET fails to improve survival
Key clinical point: Addition of palbociclib to adjuvant endocrine therapy (ET) vs. ET alone failed to improve invasive disease-free survival (IDFS) in patients with early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer.
Major finding: At the median follow-up of 23.7 months, 3-year IDFS was similar for palbociclib + ET and ET alone groups (88.2% vs. 88.5%; hazard ratio, 0.93; log-rank P = .51). Serious adverse events occurred in 12.4% of patients on palbociclib + ET vs. 7.6% on ET alone.
Study details: Findings are from the second interim analysis of the ongoing phase 3 PALLAS trial that randomly allocated 5,760 patients with stage II-III HR+ and HER2− breast cancer to receive either 2 years of palbociclib in addition to ongoing standard adjuvant ET (n = 2,883) or ongoing standard adjuvant ET alone (n = 2,877).
Disclosures: PALLAS trial was cosponsored by the Alliance Foundation Trials and the Austrian Breast and Colorectal Cancer Study Group, in collaboration with Eastern Cooperative Oncology Group, the National Surgical Adjuvant Breast and Bowel Project, the German Breast Group, and the Breast International Group, with funding from Pfizer. The lead author reported receiving personal fees from Eisai, Lilly, and Novartis. Some of the coinvestigators reported ties with various pharmaceutical companies including Pfizer.
Source: Mayer EL et al. Lancet Oncol. 2021 Jan 15. doi: 10.1016/S1470-2045(20)30642-2.
Key clinical point: Addition of palbociclib to adjuvant endocrine therapy (ET) vs. ET alone failed to improve invasive disease-free survival (IDFS) in patients with early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer.
Major finding: At the median follow-up of 23.7 months, 3-year IDFS was similar for palbociclib + ET and ET alone groups (88.2% vs. 88.5%; hazard ratio, 0.93; log-rank P = .51). Serious adverse events occurred in 12.4% of patients on palbociclib + ET vs. 7.6% on ET alone.
Study details: Findings are from the second interim analysis of the ongoing phase 3 PALLAS trial that randomly allocated 5,760 patients with stage II-III HR+ and HER2− breast cancer to receive either 2 years of palbociclib in addition to ongoing standard adjuvant ET (n = 2,883) or ongoing standard adjuvant ET alone (n = 2,877).
Disclosures: PALLAS trial was cosponsored by the Alliance Foundation Trials and the Austrian Breast and Colorectal Cancer Study Group, in collaboration with Eastern Cooperative Oncology Group, the National Surgical Adjuvant Breast and Bowel Project, the German Breast Group, and the Breast International Group, with funding from Pfizer. The lead author reported receiving personal fees from Eisai, Lilly, and Novartis. Some of the coinvestigators reported ties with various pharmaceutical companies including Pfizer.
Source: Mayer EL et al. Lancet Oncol. 2021 Jan 15. doi: 10.1016/S1470-2045(20)30642-2.
Key clinical point: Addition of palbociclib to adjuvant endocrine therapy (ET) vs. ET alone failed to improve invasive disease-free survival (IDFS) in patients with early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer.
Major finding: At the median follow-up of 23.7 months, 3-year IDFS was similar for palbociclib + ET and ET alone groups (88.2% vs. 88.5%; hazard ratio, 0.93; log-rank P = .51). Serious adverse events occurred in 12.4% of patients on palbociclib + ET vs. 7.6% on ET alone.
Study details: Findings are from the second interim analysis of the ongoing phase 3 PALLAS trial that randomly allocated 5,760 patients with stage II-III HR+ and HER2− breast cancer to receive either 2 years of palbociclib in addition to ongoing standard adjuvant ET (n = 2,883) or ongoing standard adjuvant ET alone (n = 2,877).
Disclosures: PALLAS trial was cosponsored by the Alliance Foundation Trials and the Austrian Breast and Colorectal Cancer Study Group, in collaboration with Eastern Cooperative Oncology Group, the National Surgical Adjuvant Breast and Bowel Project, the German Breast Group, and the Breast International Group, with funding from Pfizer. The lead author reported receiving personal fees from Eisai, Lilly, and Novartis. Some of the coinvestigators reported ties with various pharmaceutical companies including Pfizer.
Source: Mayer EL et al. Lancet Oncol. 2021 Jan 15. doi: 10.1016/S1470-2045(20)30642-2.