MDedge ObGyn

Physicians who misuse the “copy-and-paste” feature in patients’ electronic health records (EHRs) can face serious consequences, including lost hospital privileges, fines, and malpractice lawsuits.

In California, a locum tenens physician lost her hospital privileges after repeatedly violating the copy-and-paste policy developed at Santa Rosa Memorial Hospital, Santa Rosa, California.

“Her use of copy and paste impaired continuity of care,” said Alvin Gore, MD, who was involved in the case as the hospital’s director of utilization management.

Dr. Gore said the hospital warned the doctor, but she did not change her behavior. He did not identify the physician, citing confidentiality. The case occurred more than 5 years ago. Since then, several physicians have been called onto the carpet for violations of the policy, but no one else has lost privileges, Dr. Gore said.

Copy-paste practices can save doctors’ time when dealing with cumbersome EHR systems, but they also can lead to redundant, outdated, or inconsistent information that can compromise patient care, experts said.

“EHRs are imperfect, time consuming, and somewhat rigid,” said Robert A. Dowling, MD, a practice management consultant for large medical groups. “If physicians can’t easily figure out a complex system, they’re likely to use a workaround like copy and paste.”

Copy-and-paste abuse has also led to fines. A six-member cardiology group in Somerville, New Jersey, paid a $422,000 fine to the federal government to settle copy-and-paste charges, following an investigation by the Office of the Inspector General of the Department of Health and Human Services, according to the Report on Medicare Compliance.

This big settlement, announced in 2016, is a rare case in which physicians were charged with copy-and-paste fraud — intentionally using it to enhance reimbursement.

More commonly, Medicare contractors identify physicians who unintentionally received overpayments through sloppy copy-and-paste practices, according to a coding and documentation auditor who worked for 10 years at a Medicare contractor in Pennsylvania.

Such cases are frequent and are handled confidentially, said the auditor, who asked not to be identified. Practices must return the overpayment, and the physicians involved are “contacted and educated,” she said.

Copy and paste can also show up in malpractice lawsuits. In a 2012 survey, 53% of professional liability carriers said they had handled an EHR-related malpractice claim, and 71% of those claims included copy-and-paste use.

One such case, described by CRICO, a malpractice carrier based in Massachusetts, took place in 2012-2013. “A patient developed amiodarone toxicity because the patient›s history and medications were copied from a previous note that did not document that the patient was already on the medication,» CRICO stated.

“If you do face a malpractice claim, copying and pasting the same note repeatedly makes you look clinically inattentive, even if the copy/pasted material is unrelated to the adverse event,” CRICO officials noted in a report.
 

The Push to Use Copy and Paste

Copy and paste is a great time-saver. One study linked its use to lower burnout rates. However, it can easily introduce errors into the medical record. “This can be a huge problem,” Dr. Dowling said. “If, for example, you copy forward a previous note that said the patient had blood in their urine ‘6 days ago,’ it is immediately inaccurate.”

Practices can control use of copy and paste through coding clerks who read the medical records and then educate doctors when problems crop up.

The Pennsylvania auditor, who now works for a large group practice, said the group has very few copy-and-paste problems because of her role. “Not charting responsibly rarely happens because I work very closely with the doctors,” she said.

Dr. Dowling, however, reports that many physicians continue to overuse copy and paste. He points to a 2022 study which found that, on average, half the clinical note at one health system had been copied and pasted.

One solution might be to sanction physicians for overusing copy and paste, just as they’re sometimes penalized for not completing their notes on time with a reduction in income or possible termination.

Practices could periodically audit medical records for excessive copy-paste use. EHR systems like Epic’s can indicate how much of a doctor’s note has been copied. But Dr. Dowling doesn’t know of any practices that do this.

“There is little appetite to introduce a new enforcement activity for physicians,” he said. “Physicians would see it just as a way to make their lives more difficult than they already are.”
 

Monitoring in Hospitals and Health Systems

Some hospitals and health systems have gone as far as disabling copy-and-paste function in their EHR systems. However, enterprising physicians have found ways around these blocks.

Some institutions have also introduced formal policies, directing doctors on how they can copy and paste, including Banner Health in Arizona, Northwell Health in New York, UConn Health in Connecticut, University of Maryland Medical System, and University of Toledo in Ohio.

Definitions of what is not acceptable vary, but most of these policies oppose copying someone else’s notes and direct physicians to indicate the origin of pasted material.

Santa Rosa Memorial’s policy is quite specific. It still allows some copy and paste but stipulates that it cannot be used for the chief complaint, the review of systems, the physical examination, and the assessment and plan in the medical record, except when the information can’t be obtained directly from the patient. Also, physicians must summarize test results and provide references to other providers’ notes.

Dr. Gore said he and a physician educator who works with physicians on clinical documentation proposed the policy about a decade ago. When physicians on staff were asked to comment, some said they would be opposed to a complete ban, but they generally agreed that copy and paste was a serious problem that needed to be addressed, he said.

The hospital could have simply adopted guidelines, as opposed to rules with consequences, but “we wanted our policy to have teeth,” Dr. Gore said.

When violators are identified, Dr. Gore says he meets with them confidentially and educates them on proper use of copy and paste. Sometimes, the department head is brought in. Some physicians go on to violate the policy again and have to attend another meeting, he said, but aside from the one case, no one else has been disciplined.

It’s unclear how many physicians have faced consequences for misusing copy-paste features — such data aren’t tracked, and sanctions are likely to be handled confidentially, as a personnel matter.

Geisinger Health in Pennsylvania regularly monitors copy-and-paste usage and makes it part of physicians’ professional evaluations, according to a 2022 presentation by a Geisinger official.

Meanwhile, even when systems don’t have specific policies, they may still discipline physicians when copy and paste leads to errors. Scott MacDonald, MD, chief medical information officer at UC Davis Health in Sacramento, California, told this news organization that copy-and-paste abuse has come up a few times over the years in investigations of clinical errors.
 

Holding Physicians Accountable

Physicians can be held accountable for copy and paste by Medicare contractors and in malpractice lawsuits, but the most obvious way is at their place of work: A practice, hospital, or health system.

One physician has lost staff privileges, but more typically, coding clerks or colleagues talk to offending physicians and try to educate them on proper use of copy and paste.

Educational outreach, however, is often ineffective, said Robert Hirschtick, MD, a retired teaching physician at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “The physician may be directed to take an online course,” he said. “When they take the course, the goal is to get it done with, rather than to learn something new.”

Dr. Hirschtick’s articles on copy and paste, including one titled, “Sloppy and Paste,” have put him at the front lines of the debate. “This is an ethical issue,” he said in an interview. He agrees that some forms of copy and paste are permissible, but in many cases, “it is intellectually dishonest and potentially even plagiarism,” he said.

Dr. Hirschtick argues that copy-and-paste policies need more teeth. “Tying violations to compensation would be quite effective,” he said. “Even if physicians were rarely penalized, just knowing that it could happen to you might be enough. But I haven’t heard of anyone doing this.”

A version of this article appeared on Medscape.com.

Physicians who misuse the “copy-and-paste” feature in patients’ electronic health records (EHRs) can face serious consequences, including lost hospital privileges, fines, and malpractice lawsuits.

In California, a locum tenens physician lost her hospital privileges after repeatedly violating the copy-and-paste policy developed at Santa Rosa Memorial Hospital, Santa Rosa, California.

“Her use of copy and paste impaired continuity of care,” said Alvin Gore, MD, who was involved in the case as the hospital’s director of utilization management.

Dr. Gore said the hospital warned the doctor, but she did not change her behavior. He did not identify the physician, citing confidentiality. The case occurred more than 5 years ago. Since then, several physicians have been called onto the carpet for violations of the policy, but no one else has lost privileges, Dr. Gore said.

Copy-paste practices can save doctors’ time when dealing with cumbersome EHR systems, but they also can lead to redundant, outdated, or inconsistent information that can compromise patient care, experts said.

“EHRs are imperfect, time consuming, and somewhat rigid,” said Robert A. Dowling, MD, a practice management consultant for large medical groups. “If physicians can’t easily figure out a complex system, they’re likely to use a workaround like copy and paste.”

Copy-and-paste abuse has also led to fines. A six-member cardiology group in Somerville, New Jersey, paid a $422,000 fine to the federal government to settle copy-and-paste charges, following an investigation by the Office of the Inspector General of the Department of Health and Human Services, according to the Report on Medicare Compliance.

This big settlement, announced in 2016, is a rare case in which physicians were charged with copy-and-paste fraud — intentionally using it to enhance reimbursement.

More commonly, Medicare contractors identify physicians who unintentionally received overpayments through sloppy copy-and-paste practices, according to a coding and documentation auditor who worked for 10 years at a Medicare contractor in Pennsylvania.

Such cases are frequent and are handled confidentially, said the auditor, who asked not to be identified. Practices must return the overpayment, and the physicians involved are “contacted and educated,” she said.

Copy and paste can also show up in malpractice lawsuits. In a 2012 survey, 53% of professional liability carriers said they had handled an EHR-related malpractice claim, and 71% of those claims included copy-and-paste use.

One such case, described by CRICO, a malpractice carrier based in Massachusetts, took place in 2012-2013. “A patient developed amiodarone toxicity because the patient›s history and medications were copied from a previous note that did not document that the patient was already on the medication,» CRICO stated.

“If you do face a malpractice claim, copying and pasting the same note repeatedly makes you look clinically inattentive, even if the copy/pasted material is unrelated to the adverse event,” CRICO officials noted in a report.
 

The Push to Use Copy and Paste

Copy and paste is a great time-saver. One study linked its use to lower burnout rates. However, it can easily introduce errors into the medical record. “This can be a huge problem,” Dr. Dowling said. “If, for example, you copy forward a previous note that said the patient had blood in their urine ‘6 days ago,’ it is immediately inaccurate.”

Practices can control use of copy and paste through coding clerks who read the medical records and then educate doctors when problems crop up.

The Pennsylvania auditor, who now works for a large group practice, said the group has very few copy-and-paste problems because of her role. “Not charting responsibly rarely happens because I work very closely with the doctors,” she said.

Dr. Dowling, however, reports that many physicians continue to overuse copy and paste. He points to a 2022 study which found that, on average, half the clinical note at one health system had been copied and pasted.

One solution might be to sanction physicians for overusing copy and paste, just as they’re sometimes penalized for not completing their notes on time with a reduction in income or possible termination.

Practices could periodically audit medical records for excessive copy-paste use. EHR systems like Epic’s can indicate how much of a doctor’s note has been copied. But Dr. Dowling doesn’t know of any practices that do this.

“There is little appetite to introduce a new enforcement activity for physicians,” he said. “Physicians would see it just as a way to make their lives more difficult than they already are.”
 

Monitoring in Hospitals and Health Systems

Some hospitals and health systems have gone as far as disabling copy-and-paste function in their EHR systems. However, enterprising physicians have found ways around these blocks.

Some institutions have also introduced formal policies, directing doctors on how they can copy and paste, including Banner Health in Arizona, Northwell Health in New York, UConn Health in Connecticut, University of Maryland Medical System, and University of Toledo in Ohio.

Definitions of what is not acceptable vary, but most of these policies oppose copying someone else’s notes and direct physicians to indicate the origin of pasted material.

Santa Rosa Memorial’s policy is quite specific. It still allows some copy and paste but stipulates that it cannot be used for the chief complaint, the review of systems, the physical examination, and the assessment and plan in the medical record, except when the information can’t be obtained directly from the patient. Also, physicians must summarize test results and provide references to other providers’ notes.

Dr. Gore said he and a physician educator who works with physicians on clinical documentation proposed the policy about a decade ago. When physicians on staff were asked to comment, some said they would be opposed to a complete ban, but they generally agreed that copy and paste was a serious problem that needed to be addressed, he said.

The hospital could have simply adopted guidelines, as opposed to rules with consequences, but “we wanted our policy to have teeth,” Dr. Gore said.

When violators are identified, Dr. Gore says he meets with them confidentially and educates them on proper use of copy and paste. Sometimes, the department head is brought in. Some physicians go on to violate the policy again and have to attend another meeting, he said, but aside from the one case, no one else has been disciplined.

It’s unclear how many physicians have faced consequences for misusing copy-paste features — such data aren’t tracked, and sanctions are likely to be handled confidentially, as a personnel matter.

Geisinger Health in Pennsylvania regularly monitors copy-and-paste usage and makes it part of physicians’ professional evaluations, according to a 2022 presentation by a Geisinger official.

Meanwhile, even when systems don’t have specific policies, they may still discipline physicians when copy and paste leads to errors. Scott MacDonald, MD, chief medical information officer at UC Davis Health in Sacramento, California, told this news organization that copy-and-paste abuse has come up a few times over the years in investigations of clinical errors.
 

Holding Physicians Accountable

Physicians can be held accountable for copy and paste by Medicare contractors and in malpractice lawsuits, but the most obvious way is at their place of work: A practice, hospital, or health system.

One physician has lost staff privileges, but more typically, coding clerks or colleagues talk to offending physicians and try to educate them on proper use of copy and paste.

Educational outreach, however, is often ineffective, said Robert Hirschtick, MD, a retired teaching physician at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “The physician may be directed to take an online course,” he said. “When they take the course, the goal is to get it done with, rather than to learn something new.”

Dr. Hirschtick’s articles on copy and paste, including one titled, “Sloppy and Paste,” have put him at the front lines of the debate. “This is an ethical issue,” he said in an interview. He agrees that some forms of copy and paste are permissible, but in many cases, “it is intellectually dishonest and potentially even plagiarism,” he said.

Dr. Hirschtick argues that copy-and-paste policies need more teeth. “Tying violations to compensation would be quite effective,” he said. “Even if physicians were rarely penalized, just knowing that it could happen to you might be enough. But I haven’t heard of anyone doing this.”

A version of this article appeared on Medscape.com.

Physicians who misuse the “copy-and-paste” feature in patients’ electronic health records (EHRs) can face serious consequences, including lost hospital privileges, fines, and malpractice lawsuits.

In California, a locum tenens physician lost her hospital privileges after repeatedly violating the copy-and-paste policy developed at Santa Rosa Memorial Hospital, Santa Rosa, California.

“Her use of copy and paste impaired continuity of care,” said Alvin Gore, MD, who was involved in the case as the hospital’s director of utilization management.

Dr. Gore said the hospital warned the doctor, but she did not change her behavior. He did not identify the physician, citing confidentiality. The case occurred more than 5 years ago. Since then, several physicians have been called onto the carpet for violations of the policy, but no one else has lost privileges, Dr. Gore said.

Copy-paste practices can save doctors’ time when dealing with cumbersome EHR systems, but they also can lead to redundant, outdated, or inconsistent information that can compromise patient care, experts said.

“EHRs are imperfect, time consuming, and somewhat rigid,” said Robert A. Dowling, MD, a practice management consultant for large medical groups. “If physicians can’t easily figure out a complex system, they’re likely to use a workaround like copy and paste.”

Copy-and-paste abuse has also led to fines. A six-member cardiology group in Somerville, New Jersey, paid a $422,000 fine to the federal government to settle copy-and-paste charges, following an investigation by the Office of the Inspector General of the Department of Health and Human Services, according to the Report on Medicare Compliance.

This big settlement, announced in 2016, is a rare case in which physicians were charged with copy-and-paste fraud — intentionally using it to enhance reimbursement.

More commonly, Medicare contractors identify physicians who unintentionally received overpayments through sloppy copy-and-paste practices, according to a coding and documentation auditor who worked for 10 years at a Medicare contractor in Pennsylvania.

Such cases are frequent and are handled confidentially, said the auditor, who asked not to be identified. Practices must return the overpayment, and the physicians involved are “contacted and educated,” she said.

Copy and paste can also show up in malpractice lawsuits. In a 2012 survey, 53% of professional liability carriers said they had handled an EHR-related malpractice claim, and 71% of those claims included copy-and-paste use.

One such case, described by CRICO, a malpractice carrier based in Massachusetts, took place in 2012-2013. “A patient developed amiodarone toxicity because the patient›s history and medications were copied from a previous note that did not document that the patient was already on the medication,» CRICO stated.

“If you do face a malpractice claim, copying and pasting the same note repeatedly makes you look clinically inattentive, even if the copy/pasted material is unrelated to the adverse event,” CRICO officials noted in a report.
 

The Push to Use Copy and Paste

Copy and paste is a great time-saver. One study linked its use to lower burnout rates. However, it can easily introduce errors into the medical record. “This can be a huge problem,” Dr. Dowling said. “If, for example, you copy forward a previous note that said the patient had blood in their urine ‘6 days ago,’ it is immediately inaccurate.”

Practices can control use of copy and paste through coding clerks who read the medical records and then educate doctors when problems crop up.

The Pennsylvania auditor, who now works for a large group practice, said the group has very few copy-and-paste problems because of her role. “Not charting responsibly rarely happens because I work very closely with the doctors,” she said.

Dr. Dowling, however, reports that many physicians continue to overuse copy and paste. He points to a 2022 study which found that, on average, half the clinical note at one health system had been copied and pasted.

One solution might be to sanction physicians for overusing copy and paste, just as they’re sometimes penalized for not completing their notes on time with a reduction in income or possible termination.

Practices could periodically audit medical records for excessive copy-paste use. EHR systems like Epic’s can indicate how much of a doctor’s note has been copied. But Dr. Dowling doesn’t know of any practices that do this.

“There is little appetite to introduce a new enforcement activity for physicians,” he said. “Physicians would see it just as a way to make their lives more difficult than they already are.”
 

Monitoring in Hospitals and Health Systems

Some hospitals and health systems have gone as far as disabling copy-and-paste function in their EHR systems. However, enterprising physicians have found ways around these blocks.

Some institutions have also introduced formal policies, directing doctors on how they can copy and paste, including Banner Health in Arizona, Northwell Health in New York, UConn Health in Connecticut, University of Maryland Medical System, and University of Toledo in Ohio.

Definitions of what is not acceptable vary, but most of these policies oppose copying someone else’s notes and direct physicians to indicate the origin of pasted material.

Santa Rosa Memorial’s policy is quite specific. It still allows some copy and paste but stipulates that it cannot be used for the chief complaint, the review of systems, the physical examination, and the assessment and plan in the medical record, except when the information can’t be obtained directly from the patient. Also, physicians must summarize test results and provide references to other providers’ notes.

Dr. Gore said he and a physician educator who works with physicians on clinical documentation proposed the policy about a decade ago. When physicians on staff were asked to comment, some said they would be opposed to a complete ban, but they generally agreed that copy and paste was a serious problem that needed to be addressed, he said.

The hospital could have simply adopted guidelines, as opposed to rules with consequences, but “we wanted our policy to have teeth,” Dr. Gore said.

When violators are identified, Dr. Gore says he meets with them confidentially and educates them on proper use of copy and paste. Sometimes, the department head is brought in. Some physicians go on to violate the policy again and have to attend another meeting, he said, but aside from the one case, no one else has been disciplined.

It’s unclear how many physicians have faced consequences for misusing copy-paste features — such data aren’t tracked, and sanctions are likely to be handled confidentially, as a personnel matter.

Geisinger Health in Pennsylvania regularly monitors copy-and-paste usage and makes it part of physicians’ professional evaluations, according to a 2022 presentation by a Geisinger official.

Meanwhile, even when systems don’t have specific policies, they may still discipline physicians when copy and paste leads to errors. Scott MacDonald, MD, chief medical information officer at UC Davis Health in Sacramento, California, told this news organization that copy-and-paste abuse has come up a few times over the years in investigations of clinical errors.
 

Holding Physicians Accountable

Physicians can be held accountable for copy and paste by Medicare contractors and in malpractice lawsuits, but the most obvious way is at their place of work: A practice, hospital, or health system.

One physician has lost staff privileges, but more typically, coding clerks or colleagues talk to offending physicians and try to educate them on proper use of copy and paste.

Educational outreach, however, is often ineffective, said Robert Hirschtick, MD, a retired teaching physician at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “The physician may be directed to take an online course,” he said. “When they take the course, the goal is to get it done with, rather than to learn something new.”

Dr. Hirschtick’s articles on copy and paste, including one titled, “Sloppy and Paste,” have put him at the front lines of the debate. “This is an ethical issue,” he said in an interview. He agrees that some forms of copy and paste are permissible, but in many cases, “it is intellectually dishonest and potentially even plagiarism,” he said.

Dr. Hirschtick argues that copy-and-paste policies need more teeth. “Tying violations to compensation would be quite effective,” he said. “Even if physicians were rarely penalized, just knowing that it could happen to you might be enough. But I haven’t heard of anyone doing this.”

A version of this article appeared on Medscape.com.

Hormone Therapy (HT) is a good option for most women over age 65, despite entrenched fears about HT safety, according to findings from a new study published in Menopause.

The study, led by Seo H. Baik, PhD, of Lister Hill National Center for Biomedical Communications, National Library of Medicine, in Bethesda, Maryland, and colleagues is based on the health records of 10 million senior women on Medicare from 2007 to 2020. It concludes there are important health benefits with HT beyond age 65 and the effects of using HT after age 65 vary by type of therapy, route of administration, and dose.
 

Controversial Since Women’s Health Initiative

Use of HT after age 65 has been controversial in light of the findings of the Women’s Health Initiative (WHI) study in 2002. Since that study, many women have decided against HT, especially after age 65, because of fears of increased risks for cancers and heart disease.

Baik et al. concluded that, compared with never using or stopping use of HT before the age of 65 years, the use of estrogen alone beyond age 65 years was associated with the following significant risk reductions: mortality (19%); breast cancer (16%); lung cancer (13%); colorectal cancer (12%); congestive heart failure (5%); venous thromboembolism (5%); atrial fibrillation (4%); acute myocardial infarction (11%); and dementia (2%).

The authors further found that estrogen plus progestin was associated with significant risk reductions in endometrial cancer (45%); ovarian cancer (21%); ischemic heart disease (5%); congestive heart failure (5%); and venous thromboembolism (5%).

Estrogen plus progesterone, however, was linked with risk reduction only in congestive heart failure (4%).

Reassuring Results

“These results should provide additional reassurance to women about hormone therapy,” said Lisa C, Larkin, MD, president of The Menopause Society. “This data is largely consistent with the WHI data as we understand it today — that for the majority of women with symptoms transitioning through menopause, hormone therapy is the most effective treatment and has benefits that outweigh risks.”

There may be some exceptions, she noted, particularly in older women with high risk for cardiovascular disease and stroke. Among those women, she explained, the risks of HT may outweigh the benefits and it may be appropriate to stop hormone therapy.

“In these older women with specific risk factors, the discussion of continuing or stopping HT is nuanced and complex and must involve shared decision-making,” she said.

Elevated Breast Cancer Risk Can be Mitigated

With a therapy combining estrogen and progestogen, both estrogen plus progestin and estrogen plus progesterone were associated with a 10%-19% increased risk of breast cancer, but the authors say that risk can be mitigated using low doses of transdermal or vaginal estrogen plus progestin.

“In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 (estradiol) rather than conjugated estrogen,” the authors write.

The authors report that over 14 years of follow-up (from 2007 to 2020), the proportion of senior women taking any HT-containing estrogen dropped by half, from 11.4% to 5.5%. E2 has largely replaced conjugated estrogen (CEE); and vaginal administration largely replaced oral.

Controversy Remains

Even with these results, hormone use will remain controversial, Dr. Larkin said, without enormous efforts to educate. Menopausal HT therapy in young 50-year-old women having symptoms is still controversial — despite the large body of evidence supporting safety and benefit in the majority of women, she said.

“For the last 25 years we have completely neglected education of clinicians about menopause and the data on hormone therapy,” she said. “As a result, most of the clinicians practicing do not understand the data and remain very negative about hormones even in younger women. The decades of lack of education of clinicians about menopause is one of the major reasons far too many young, healthy, 50-year-old women with symptoms are not getting the care they need [hormone therapy] at menopause.” Instead, she says, women are told to take supplements because some providers think hormone therapy is too dangerous.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University’s Feinberg School of Medicine, and founding director of the Northwestern Medical Center for Sexual Medicine and Menopause, both in Chicago, says, “In the WHI, 70% of the women were over the age of 65 when they initiated therapy, which partially accounts for the negative outcomes. In addition, in WHI, everyone was taking oral [HT]. This (current) data is very reassuring — and validating — for women who would like to continue taking HT.”

Dr. Streicher says women who would like to start HT after 65 should be counseled on individual risks and after cardiac health is evaluated. But, she notes, this study did not address that.

‘Best Time to Stop HT is When You Die’

She says in her practice she will counsel women who are on HT and would like to continue after age 65 the way she always has: “If someone is taking HT and has no specific reason to stop, there is no reason to stop at some arbitrary age or time and that if they do, they will lose many of the benefits,” particularly bone, cognitive, cardiovascular, and vulvovaginal benefits, she explained. “The best time to stop HT is when you die,” Dr. Streicher said, “And, given the reduction in mortality in women who take HT, that will be at a much older age than women who don’t take HT.”

So will these new data be convincing?

“It will convince the already convinced — menopause experts who follow the data. It is the rare menopause expert that tells women to stop HT,” Dr. Streicher said.

However, she said, “The overwhelming majority of clinicians in the US currently do not prescribe HT. Sadly, I don’t think this will change much.”

The authors report no relevant financial relationships. Dr. Larkin consults for several women’s health companies including Mayne Pharma, Astellas, Johnson & Johnson, Grail, Pfizer, and Solv Wellness. Dr. Streicher reports no relevant financial relationships.

Hormone Therapy (HT) is a good option for most women over age 65, despite entrenched fears about HT safety, according to findings from a new study published in Menopause.

The study, led by Seo H. Baik, PhD, of Lister Hill National Center for Biomedical Communications, National Library of Medicine, in Bethesda, Maryland, and colleagues is based on the health records of 10 million senior women on Medicare from 2007 to 2020. It concludes there are important health benefits with HT beyond age 65 and the effects of using HT after age 65 vary by type of therapy, route of administration, and dose.
 

Controversial Since Women’s Health Initiative

Use of HT after age 65 has been controversial in light of the findings of the Women’s Health Initiative (WHI) study in 2002. Since that study, many women have decided against HT, especially after age 65, because of fears of increased risks for cancers and heart disease.

Baik et al. concluded that, compared with never using or stopping use of HT before the age of 65 years, the use of estrogen alone beyond age 65 years was associated with the following significant risk reductions: mortality (19%); breast cancer (16%); lung cancer (13%); colorectal cancer (12%); congestive heart failure (5%); venous thromboembolism (5%); atrial fibrillation (4%); acute myocardial infarction (11%); and dementia (2%).

The authors further found that estrogen plus progestin was associated with significant risk reductions in endometrial cancer (45%); ovarian cancer (21%); ischemic heart disease (5%); congestive heart failure (5%); and venous thromboembolism (5%).

Estrogen plus progesterone, however, was linked with risk reduction only in congestive heart failure (4%).

Reassuring Results

“These results should provide additional reassurance to women about hormone therapy,” said Lisa C, Larkin, MD, president of The Menopause Society. “This data is largely consistent with the WHI data as we understand it today — that for the majority of women with symptoms transitioning through menopause, hormone therapy is the most effective treatment and has benefits that outweigh risks.”

There may be some exceptions, she noted, particularly in older women with high risk for cardiovascular disease and stroke. Among those women, she explained, the risks of HT may outweigh the benefits and it may be appropriate to stop hormone therapy.

“In these older women with specific risk factors, the discussion of continuing or stopping HT is nuanced and complex and must involve shared decision-making,” she said.

Elevated Breast Cancer Risk Can be Mitigated

With a therapy combining estrogen and progestogen, both estrogen plus progestin and estrogen plus progesterone were associated with a 10%-19% increased risk of breast cancer, but the authors say that risk can be mitigated using low doses of transdermal or vaginal estrogen plus progestin.

“In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 (estradiol) rather than conjugated estrogen,” the authors write.

The authors report that over 14 years of follow-up (from 2007 to 2020), the proportion of senior women taking any HT-containing estrogen dropped by half, from 11.4% to 5.5%. E2 has largely replaced conjugated estrogen (CEE); and vaginal administration largely replaced oral.

Controversy Remains

Even with these results, hormone use will remain controversial, Dr. Larkin said, without enormous efforts to educate. Menopausal HT therapy in young 50-year-old women having symptoms is still controversial — despite the large body of evidence supporting safety and benefit in the majority of women, she said.

“For the last 25 years we have completely neglected education of clinicians about menopause and the data on hormone therapy,” she said. “As a result, most of the clinicians practicing do not understand the data and remain very negative about hormones even in younger women. The decades of lack of education of clinicians about menopause is one of the major reasons far too many young, healthy, 50-year-old women with symptoms are not getting the care they need [hormone therapy] at menopause.” Instead, she says, women are told to take supplements because some providers think hormone therapy is too dangerous.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University’s Feinberg School of Medicine, and founding director of the Northwestern Medical Center for Sexual Medicine and Menopause, both in Chicago, says, “In the WHI, 70% of the women were over the age of 65 when they initiated therapy, which partially accounts for the negative outcomes. In addition, in WHI, everyone was taking oral [HT]. This (current) data is very reassuring — and validating — for women who would like to continue taking HT.”

Dr. Streicher says women who would like to start HT after 65 should be counseled on individual risks and after cardiac health is evaluated. But, she notes, this study did not address that.

‘Best Time to Stop HT is When You Die’

She says in her practice she will counsel women who are on HT and would like to continue after age 65 the way she always has: “If someone is taking HT and has no specific reason to stop, there is no reason to stop at some arbitrary age or time and that if they do, they will lose many of the benefits,” particularly bone, cognitive, cardiovascular, and vulvovaginal benefits, she explained. “The best time to stop HT is when you die,” Dr. Streicher said, “And, given the reduction in mortality in women who take HT, that will be at a much older age than women who don’t take HT.”

So will these new data be convincing?

“It will convince the already convinced — menopause experts who follow the data. It is the rare menopause expert that tells women to stop HT,” Dr. Streicher said.

However, she said, “The overwhelming majority of clinicians in the US currently do not prescribe HT. Sadly, I don’t think this will change much.”

The authors report no relevant financial relationships. Dr. Larkin consults for several women’s health companies including Mayne Pharma, Astellas, Johnson & Johnson, Grail, Pfizer, and Solv Wellness. Dr. Streicher reports no relevant financial relationships.

Hormone Therapy (HT) is a good option for most women over age 65, despite entrenched fears about HT safety, according to findings from a new study published in Menopause.

The study, led by Seo H. Baik, PhD, of Lister Hill National Center for Biomedical Communications, National Library of Medicine, in Bethesda, Maryland, and colleagues is based on the health records of 10 million senior women on Medicare from 2007 to 2020. It concludes there are important health benefits with HT beyond age 65 and the effects of using HT after age 65 vary by type of therapy, route of administration, and dose.
 

Controversial Since Women’s Health Initiative

Use of HT after age 65 has been controversial in light of the findings of the Women’s Health Initiative (WHI) study in 2002. Since that study, many women have decided against HT, especially after age 65, because of fears of increased risks for cancers and heart disease.

Baik et al. concluded that, compared with never using or stopping use of HT before the age of 65 years, the use of estrogen alone beyond age 65 years was associated with the following significant risk reductions: mortality (19%); breast cancer (16%); lung cancer (13%); colorectal cancer (12%); congestive heart failure (5%); venous thromboembolism (5%); atrial fibrillation (4%); acute myocardial infarction (11%); and dementia (2%).

The authors further found that estrogen plus progestin was associated with significant risk reductions in endometrial cancer (45%); ovarian cancer (21%); ischemic heart disease (5%); congestive heart failure (5%); and venous thromboembolism (5%).

Estrogen plus progesterone, however, was linked with risk reduction only in congestive heart failure (4%).

Reassuring Results

“These results should provide additional reassurance to women about hormone therapy,” said Lisa C, Larkin, MD, president of The Menopause Society. “This data is largely consistent with the WHI data as we understand it today — that for the majority of women with symptoms transitioning through menopause, hormone therapy is the most effective treatment and has benefits that outweigh risks.”

There may be some exceptions, she noted, particularly in older women with high risk for cardiovascular disease and stroke. Among those women, she explained, the risks of HT may outweigh the benefits and it may be appropriate to stop hormone therapy.

“In these older women with specific risk factors, the discussion of continuing or stopping HT is nuanced and complex and must involve shared decision-making,” she said.

Elevated Breast Cancer Risk Can be Mitigated

With a therapy combining estrogen and progestogen, both estrogen plus progestin and estrogen plus progesterone were associated with a 10%-19% increased risk of breast cancer, but the authors say that risk can be mitigated using low doses of transdermal or vaginal estrogen plus progestin.

“In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 (estradiol) rather than conjugated estrogen,” the authors write.

The authors report that over 14 years of follow-up (from 2007 to 2020), the proportion of senior women taking any HT-containing estrogen dropped by half, from 11.4% to 5.5%. E2 has largely replaced conjugated estrogen (CEE); and vaginal administration largely replaced oral.

Controversy Remains

Even with these results, hormone use will remain controversial, Dr. Larkin said, without enormous efforts to educate. Menopausal HT therapy in young 50-year-old women having symptoms is still controversial — despite the large body of evidence supporting safety and benefit in the majority of women, she said.

“For the last 25 years we have completely neglected education of clinicians about menopause and the data on hormone therapy,” she said. “As a result, most of the clinicians practicing do not understand the data and remain very negative about hormones even in younger women. The decades of lack of education of clinicians about menopause is one of the major reasons far too many young, healthy, 50-year-old women with symptoms are not getting the care they need [hormone therapy] at menopause.” Instead, she says, women are told to take supplements because some providers think hormone therapy is too dangerous.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University’s Feinberg School of Medicine, and founding director of the Northwestern Medical Center for Sexual Medicine and Menopause, both in Chicago, says, “In the WHI, 70% of the women were over the age of 65 when they initiated therapy, which partially accounts for the negative outcomes. In addition, in WHI, everyone was taking oral [HT]. This (current) data is very reassuring — and validating — for women who would like to continue taking HT.”

Dr. Streicher says women who would like to start HT after 65 should be counseled on individual risks and after cardiac health is evaluated. But, she notes, this study did not address that.

‘Best Time to Stop HT is When You Die’

She says in her practice she will counsel women who are on HT and would like to continue after age 65 the way she always has: “If someone is taking HT and has no specific reason to stop, there is no reason to stop at some arbitrary age or time and that if they do, they will lose many of the benefits,” particularly bone, cognitive, cardiovascular, and vulvovaginal benefits, she explained. “The best time to stop HT is when you die,” Dr. Streicher said, “And, given the reduction in mortality in women who take HT, that will be at a much older age than women who don’t take HT.”

So will these new data be convincing?

“It will convince the already convinced — menopause experts who follow the data. It is the rare menopause expert that tells women to stop HT,” Dr. Streicher said.

However, she said, “The overwhelming majority of clinicians in the US currently do not prescribe HT. Sadly, I don’t think this will change much.”

The authors report no relevant financial relationships. Dr. Larkin consults for several women’s health companies including Mayne Pharma, Astellas, Johnson & Johnson, Grail, Pfizer, and Solv Wellness. Dr. Streicher reports no relevant financial relationships.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

BUDAPEST, Hungary — A single dose of intravenous esketamine during delivery or cesarean section appears to reduce the risk for postpartum depression (PPD) by more than 50% in the first 6 weeks, a new meta-analysis suggested. However, the long-term safety and efficacy of the drug are still unclear.

Study investigator Angelina Kozhokar, MD, Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Sant Cugat del Valles, Spain, told this news organization she was “surprised” by the size of the PPD risk reduction associated with the drug.

However, she added, “it’s important to consider that preliminary studies on a lot of medications used for postpartum depression have also shown very big effect sizes.”

Dr. Kozhokar believes that as more studies examining esketamine for PPD are conducted, “we will see more definitive effect sizes, and the safety profile for this new treatment” will become clearer.

The findings were presented at the European Psychiatric Association (EPA) Congress.
 

Significant Reduction

As previously reported by this news organization, intranasal esketamine (Spravato, Janssen) was shown to be superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression.

With up to 13% of women experiencing PPD in the perinatal period, the researchers sought to examine the impact of esketamine administered prophylactically during labor or cesarean section on the incidence of the disorder.

They searched the PubMed, Scopus, and Google Scholar databases for randomized controlled trials examining the efficacy of esketamine and screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS).

While the intranasal spray is the only form of esketamine approved by the US Food and Drug Administration, an injectable solution is also available. The researchers identified seven eligible trials that included a total of 1287 women. Of these participants, 635 (49.3%) received esketamine. Esketamine was delivered as either patient-controlled intravenous analgesia or a single intravenous dose during delivery or cesarean section.

Across the seven trials, esketamine was associated with a significant reduction in PPD at 1 week after delivery at a risk ratio vs placebo of 0.459 (P < .05). At 6 weeks, the reduction in PPD incidence was maintained, at a risk ratio of 0.470 (P < .01).

However, Dr. Kozhokar pointed out that the EPDS is a subjective measure of PPD, and the studies used different cutoff scores for depression, ranging from 9 to 13 points.
 

Unanswered Questions

She also cautioned that the adverse effects of esketamine on maternal and neonatal health need to be assessed, as well as the long-term cost/benefit ratio of prophylactic treatment.

All seven studies included in the meta-analysis were conducted in China, which limits the generalizability of the findings.

“I suppose they were quicker to get to the topic than the rest of the world,” Dr. Kozhokar said, while also suggesting that, potentially, “we are more regulated here in Europe.”

She pointed out that there is “an important safety concern about the use of medications such as ketamine and esketamine” in terms of the potential for addiction and the effect on babies over the long term, which is currently unknown.

Session chair Linda Rubene, MD, a psychiatrist in the Department of Psychiatry and Narcology at Riga Stradinš University, Riga, Latvia, welcomed the study.

“If we had more options to treat postpartum depression and to treat depression during pregnancy, it would be a great improvement,” she said.

However, she noted, because there are no long-term outcome data for esketamine in PPD, more study is needed. It is possible, said Dr. Rubene, that esketamine may not work for all women.

The investigators and Dr. Rubene reported no relevant financial disclosures.

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

BUDAPEST, Hungary — A single dose of intravenous esketamine during delivery or cesarean section appears to reduce the risk for postpartum depression (PPD) by more than 50% in the first 6 weeks, a new meta-analysis suggested. However, the long-term safety and efficacy of the drug are still unclear.

Study investigator Angelina Kozhokar, MD, Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Sant Cugat del Valles, Spain, told this news organization she was “surprised” by the size of the PPD risk reduction associated with the drug.

However, she added, “it’s important to consider that preliminary studies on a lot of medications used for postpartum depression have also shown very big effect sizes.”

Dr. Kozhokar believes that as more studies examining esketamine for PPD are conducted, “we will see more definitive effect sizes, and the safety profile for this new treatment” will become clearer.

The findings were presented at the European Psychiatric Association (EPA) Congress.
 

Significant Reduction

As previously reported by this news organization, intranasal esketamine (Spravato, Janssen) was shown to be superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression.

With up to 13% of women experiencing PPD in the perinatal period, the researchers sought to examine the impact of esketamine administered prophylactically during labor or cesarean section on the incidence of the disorder.

They searched the PubMed, Scopus, and Google Scholar databases for randomized controlled trials examining the efficacy of esketamine and screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS).

While the intranasal spray is the only form of esketamine approved by the US Food and Drug Administration, an injectable solution is also available. The researchers identified seven eligible trials that included a total of 1287 women. Of these participants, 635 (49.3%) received esketamine. Esketamine was delivered as either patient-controlled intravenous analgesia or a single intravenous dose during delivery or cesarean section.

Across the seven trials, esketamine was associated with a significant reduction in PPD at 1 week after delivery at a risk ratio vs placebo of 0.459 (P < .05). At 6 weeks, the reduction in PPD incidence was maintained, at a risk ratio of 0.470 (P < .01).

However, Dr. Kozhokar pointed out that the EPDS is a subjective measure of PPD, and the studies used different cutoff scores for depression, ranging from 9 to 13 points.
 

Unanswered Questions

She also cautioned that the adverse effects of esketamine on maternal and neonatal health need to be assessed, as well as the long-term cost/benefit ratio of prophylactic treatment.

All seven studies included in the meta-analysis were conducted in China, which limits the generalizability of the findings.

“I suppose they were quicker to get to the topic than the rest of the world,” Dr. Kozhokar said, while also suggesting that, potentially, “we are more regulated here in Europe.”

She pointed out that there is “an important safety concern about the use of medications such as ketamine and esketamine” in terms of the potential for addiction and the effect on babies over the long term, which is currently unknown.

Session chair Linda Rubene, MD, a psychiatrist in the Department of Psychiatry and Narcology at Riga Stradinš University, Riga, Latvia, welcomed the study.

“If we had more options to treat postpartum depression and to treat depression during pregnancy, it would be a great improvement,” she said.

However, she noted, because there are no long-term outcome data for esketamine in PPD, more study is needed. It is possible, said Dr. Rubene, that esketamine may not work for all women.

The investigators and Dr. Rubene reported no relevant financial disclosures.

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

BUDAPEST, Hungary — A single dose of intravenous esketamine during delivery or cesarean section appears to reduce the risk for postpartum depression (PPD) by more than 50% in the first 6 weeks, a new meta-analysis suggested. However, the long-term safety and efficacy of the drug are still unclear.

Study investigator Angelina Kozhokar, MD, Department of Medicine, Universitat Internacional de Catalunya, Barcelona, Sant Cugat del Valles, Spain, told this news organization she was “surprised” by the size of the PPD risk reduction associated with the drug.

However, she added, “it’s important to consider that preliminary studies on a lot of medications used for postpartum depression have also shown very big effect sizes.”

Dr. Kozhokar believes that as more studies examining esketamine for PPD are conducted, “we will see more definitive effect sizes, and the safety profile for this new treatment” will become clearer.

The findings were presented at the European Psychiatric Association (EPA) Congress.
 

Significant Reduction

As previously reported by this news organization, intranasal esketamine (Spravato, Janssen) was shown to be superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression.

With up to 13% of women experiencing PPD in the perinatal period, the researchers sought to examine the impact of esketamine administered prophylactically during labor or cesarean section on the incidence of the disorder.

They searched the PubMed, Scopus, and Google Scholar databases for randomized controlled trials examining the efficacy of esketamine and screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS).

While the intranasal spray is the only form of esketamine approved by the US Food and Drug Administration, an injectable solution is also available. The researchers identified seven eligible trials that included a total of 1287 women. Of these participants, 635 (49.3%) received esketamine. Esketamine was delivered as either patient-controlled intravenous analgesia or a single intravenous dose during delivery or cesarean section.

Across the seven trials, esketamine was associated with a significant reduction in PPD at 1 week after delivery at a risk ratio vs placebo of 0.459 (P < .05). At 6 weeks, the reduction in PPD incidence was maintained, at a risk ratio of 0.470 (P < .01).

However, Dr. Kozhokar pointed out that the EPDS is a subjective measure of PPD, and the studies used different cutoff scores for depression, ranging from 9 to 13 points.
 

Unanswered Questions

She also cautioned that the adverse effects of esketamine on maternal and neonatal health need to be assessed, as well as the long-term cost/benefit ratio of prophylactic treatment.

All seven studies included in the meta-analysis were conducted in China, which limits the generalizability of the findings.

“I suppose they were quicker to get to the topic than the rest of the world,” Dr. Kozhokar said, while also suggesting that, potentially, “we are more regulated here in Europe.”

She pointed out that there is “an important safety concern about the use of medications such as ketamine and esketamine” in terms of the potential for addiction and the effect on babies over the long term, which is currently unknown.

Session chair Linda Rubene, MD, a psychiatrist in the Department of Psychiatry and Narcology at Riga Stradinš University, Riga, Latvia, welcomed the study.

“If we had more options to treat postpartum depression and to treat depression during pregnancy, it would be a great improvement,” she said.

However, she noted, because there are no long-term outcome data for esketamine in PPD, more study is needed. It is possible, said Dr. Rubene, that esketamine may not work for all women.

The investigators and Dr. Rubene reported no relevant financial disclosures.

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

It should come as no surprise that when physicians speak out on social and political issues, there is sometimes a backlash. This can range from the typical trolling that occurs online to rarer cases of professional penalties. Two doctors were fired by NYU Langone Health late last year after they posted social media messages about the Israel-Hamas war. Still, many physicians are not only willing to stand up for what they believe in, but they see it as an essential part of their profession. 
"We're now at a place where doctors need to engage in public advocacy as an urgent part of our job," wrote Rob Davidson, MD, an emergency department physician, at the onslaught of the COVID-19 pandemic. In an Op-Ed piece for The Guardian, Dr. Davidson noted how the virus forced many physicians into becoming "activist doctors," calling for adequate personal protective equipment and correcting misinformation. "What we want above all is for the administration to listen to doctors, nurses, and frontline health workers - and stop playing politics," he wrote. 

'It's Not About Being Political' 

The intersection of medicine and politics is hardly new. Doctors frequently testify before Congress, sharing their expertise on issues concerning public health. This, however, isn't the same as "playing politics." 
"I'm not taking political stances," said Megan Ranney, MD, Dean of the Yale School of Public Health. "Rather, I'm using science to inform best practices, and I'm vocal around the area where I have expertise where we could do collectively better." 
Dr. Ranney's work to end firearm injury and death garnered particular attention when she co-authored an open letter to the National Rifle Association (NRA) in 2018. She wrote the letter in response to a tweet by the organization, admonishing physicians to "stay in their lane" when it comes to gun control.  
Dr. Ranney's letter discussed gun violence as a public health crisis and urged the NRA to "be part of the solution" by joining the collective effort to reduce firearm injury and death through research, education, and advocacy. "We are not anti-gun," she stated. "We are anti-bullet hole," adding that "almost half of doctors own guns." 
The NRA disagreed. When Dr. Ranney testified before Congress during a hearing on gun violence in 2023, NRA spokesperson Billy McLaughlin condemned her testimony as an effort to "dismantle the Second Amendment," calling Dr. Ranney "a known gun control extremist." 
"If you actually read what I write, or if you actually listen to what I say, I'm not saying things on behalf of one political party or another," said Dr. Ranney. "It's not about being political. It's about recognizing our role in describing what's happening and making it clear for the world to see. Showing where, based off of data, there may be a better path to improve health and wellbeing." 
In spite of the backlash, Dr. Ranney has no regrets about being an activist. "In the current media landscape, folks love to slap labels on people that may or may not be accurate. To me, what matters isn't where I land with a particular politician or political party, but how the work that I do improves health for populations." 

When the Need to Act Outweighs the Fear 

Laura Andreson, DO, an ob.gyn, took activism a step further when she joined a group of women in Tennessee to file a suit against the state, the attorney general, and the state board of medical examiners. The issue was the Tennessee's abortion ban, which the suit claimed prevented women from getting "necessary and potentially life-saving medical care."  
Dr. Andreson, who says she was "not at all" politically active in the past, began to realize how the abortion ban could drastically affect her profession and her patients. "I don't know what flipped in me, but I just felt like I could do this," she said. 
Like Dr. Ranney, Dr. Andreson has been as visible as she has been vocal, giving press conferences and interviews, but she acknowledges she has some fears about safety. In fact, after filing the lawsuit, the Center for Reproductive Rights recommended that she go to a website, DeleteMe, that removes personal data from the internet, making it more difficult for people to find her information. "But my need to do this and my desire to do this is stronger than my fears," she added. 
Dr. Andreson, who is part of a small practice, did check with both her coworkers and the hospital administration before moving forward with the lawsuit. She was relieved to find that she had the support of her practice and that there wasn't anything in the hospital bylaws to prevent her from filing the lawsuit. "But the people in the bigger institutions who probably have an even better expert base than I do, they are handcuffed," she said. 
It has been, in Dr. Andreson's words, "a little uncomfortable" being on the board of the Tennessee Medical Association when the Tennessee Board of Medical Examiners is part of the lawsuit. "We're all members of the same group," she said. "But I'm not suing them as individuals; I'm suing them as an entity that is under our government." 
Dr. Andreson said most people have been supportive of her activist work, though she admitted to feeling frustrated when she encounters apathy from fellow ob.gyns. She got little response when she circulated information explaining the abortion laws and trying to get others involved. But she still sees education as being a key part of making change happen.  
"I think advocacy, as someone who is considered a responsible, trustworthy person by your community, is important, because you can sway some people just by educating them," she said. 

Fighting Inequities in Medicine and Beyond 

Christina Chen, MD, says she felt very supported by her medical community at the Mayo Clinic in Rochester, Minnesota, when she and 16 other Asian American physicians posted a video on Instagram in 2020 highlighting increased violence and harassment of Asian Americans during COVID-19. It soon went viral, and the Mayo Clinic distributed it across their social media channels. The only negative repercussions Mayo faced were a few posts on social media saying that politics should not be brought into the healthcare space. Dr. Chen disagrees. 
"Social issues and political decisions have direct impact on the health of our communities," Dr. Chen said. "We know that we still have a long way to go to solve health inequities, which is a public health problem, and we all play a huge role in voicing our concerns." 
Activism, however, seems to be more complicated when it involves physicians being critical of inequities within the medical field. Nephrologist, Vanessa Grubbs, MD, MPH, founded the nonprofit Black Doc Village in 2022 to raise awareness about the wrongful dismissal of Black residents and expand the Black physician workforce. 
Dr. Grubbs said that the medical community has not been supportive of her activism. "The reason why I'm no longer in academia is in part because they got very upset with me tweeting about how some trainees are biased in their treatment of attendings," she said. "Senior White men attendings are often treated very differently than junior women of color faculty." 
Dr. Grubbs also expressed her views in 2020 essay in the New England Journal of Medicine where she criticized academic medical institutions for ignoring systemic racism, paying lip service to diversity, equity, and inclusion, and staying "deafeningly silent" when issues of racism are raised. 
Today, Black Doc Village is focused on conducting research that can be used to change policy. And Dr. Grubbs now has the full support of her colleagues at West Oakland Health, in Oakland, California, which aspires to advance the Bay Area Black community's health and dignity. "So, no one here has a problem with me speaking out," she added. 
The emphasis on data-driven activism as opposed to "playing politics," is a recurring theme for many physicians who publicly engage with social issues. 
"It's not partisan," Dr. Ranney said. "Rather, it's a commitment to translating science into actionable steps that can be used regardless of what political party you are in. My job is not to be on one side or the other, but to advance human health." These doctors challenge their critics to explain how such a goal is outside their purview. 
A version of this article first appeared on Medscape.com.

It should come as no surprise that when physicians speak out on social and political issues, there is sometimes a backlash. This can range from the typical trolling that occurs online to rarer cases of professional penalties. Two doctors were fired by NYU Langone Health late last year after they posted social media messages about the Israel-Hamas war. Still, many physicians are not only willing to stand up for what they believe in, but they see it as an essential part of their profession. 
"We're now at a place where doctors need to engage in public advocacy as an urgent part of our job," wrote Rob Davidson, MD, an emergency department physician, at the onslaught of the COVID-19 pandemic. In an Op-Ed piece for The Guardian, Dr. Davidson noted how the virus forced many physicians into becoming "activist doctors," calling for adequate personal protective equipment and correcting misinformation. "What we want above all is for the administration to listen to doctors, nurses, and frontline health workers - and stop playing politics," he wrote. 

'It's Not About Being Political' 

The intersection of medicine and politics is hardly new. Doctors frequently testify before Congress, sharing their expertise on issues concerning public health. This, however, isn't the same as "playing politics." 
"I'm not taking political stances," said Megan Ranney, MD, Dean of the Yale School of Public Health. "Rather, I'm using science to inform best practices, and I'm vocal around the area where I have expertise where we could do collectively better." 
Dr. Ranney's work to end firearm injury and death garnered particular attention when she co-authored an open letter to the National Rifle Association (NRA) in 2018. She wrote the letter in response to a tweet by the organization, admonishing physicians to "stay in their lane" when it comes to gun control.  
Dr. Ranney's letter discussed gun violence as a public health crisis and urged the NRA to "be part of the solution" by joining the collective effort to reduce firearm injury and death through research, education, and advocacy. "We are not anti-gun," she stated. "We are anti-bullet hole," adding that "almost half of doctors own guns." 
The NRA disagreed. When Dr. Ranney testified before Congress during a hearing on gun violence in 2023, NRA spokesperson Billy McLaughlin condemned her testimony as an effort to "dismantle the Second Amendment," calling Dr. Ranney "a known gun control extremist." 
"If you actually read what I write, or if you actually listen to what I say, I'm not saying things on behalf of one political party or another," said Dr. Ranney. "It's not about being political. It's about recognizing our role in describing what's happening and making it clear for the world to see. Showing where, based off of data, there may be a better path to improve health and wellbeing." 
In spite of the backlash, Dr. Ranney has no regrets about being an activist. "In the current media landscape, folks love to slap labels on people that may or may not be accurate. To me, what matters isn't where I land with a particular politician or political party, but how the work that I do improves health for populations." 

When the Need to Act Outweighs the Fear 

Laura Andreson, DO, an ob.gyn, took activism a step further when she joined a group of women in Tennessee to file a suit against the state, the attorney general, and the state board of medical examiners. The issue was the Tennessee's abortion ban, which the suit claimed prevented women from getting "necessary and potentially life-saving medical care."  
Dr. Andreson, who says she was "not at all" politically active in the past, began to realize how the abortion ban could drastically affect her profession and her patients. "I don't know what flipped in me, but I just felt like I could do this," she said. 
Like Dr. Ranney, Dr. Andreson has been as visible as she has been vocal, giving press conferences and interviews, but she acknowledges she has some fears about safety. In fact, after filing the lawsuit, the Center for Reproductive Rights recommended that she go to a website, DeleteMe, that removes personal data from the internet, making it more difficult for people to find her information. "But my need to do this and my desire to do this is stronger than my fears," she added. 
Dr. Andreson, who is part of a small practice, did check with both her coworkers and the hospital administration before moving forward with the lawsuit. She was relieved to find that she had the support of her practice and that there wasn't anything in the hospital bylaws to prevent her from filing the lawsuit. "But the people in the bigger institutions who probably have an even better expert base than I do, they are handcuffed," she said. 
It has been, in Dr. Andreson's words, "a little uncomfortable" being on the board of the Tennessee Medical Association when the Tennessee Board of Medical Examiners is part of the lawsuit. "We're all members of the same group," she said. "But I'm not suing them as individuals; I'm suing them as an entity that is under our government." 
Dr. Andreson said most people have been supportive of her activist work, though she admitted to feeling frustrated when she encounters apathy from fellow ob.gyns. She got little response when she circulated information explaining the abortion laws and trying to get others involved. But she still sees education as being a key part of making change happen.  
"I think advocacy, as someone who is considered a responsible, trustworthy person by your community, is important, because you can sway some people just by educating them," she said. 

Fighting Inequities in Medicine and Beyond 

Christina Chen, MD, says she felt very supported by her medical community at the Mayo Clinic in Rochester, Minnesota, when she and 16 other Asian American physicians posted a video on Instagram in 2020 highlighting increased violence and harassment of Asian Americans during COVID-19. It soon went viral, and the Mayo Clinic distributed it across their social media channels. The only negative repercussions Mayo faced were a few posts on social media saying that politics should not be brought into the healthcare space. Dr. Chen disagrees. 
"Social issues and political decisions have direct impact on the health of our communities," Dr. Chen said. "We know that we still have a long way to go to solve health inequities, which is a public health problem, and we all play a huge role in voicing our concerns." 
Activism, however, seems to be more complicated when it involves physicians being critical of inequities within the medical field. Nephrologist, Vanessa Grubbs, MD, MPH, founded the nonprofit Black Doc Village in 2022 to raise awareness about the wrongful dismissal of Black residents and expand the Black physician workforce. 
Dr. Grubbs said that the medical community has not been supportive of her activism. "The reason why I'm no longer in academia is in part because they got very upset with me tweeting about how some trainees are biased in their treatment of attendings," she said. "Senior White men attendings are often treated very differently than junior women of color faculty." 
Dr. Grubbs also expressed her views in 2020 essay in the New England Journal of Medicine where she criticized academic medical institutions for ignoring systemic racism, paying lip service to diversity, equity, and inclusion, and staying "deafeningly silent" when issues of racism are raised. 
Today, Black Doc Village is focused on conducting research that can be used to change policy. And Dr. Grubbs now has the full support of her colleagues at West Oakland Health, in Oakland, California, which aspires to advance the Bay Area Black community's health and dignity. "So, no one here has a problem with me speaking out," she added. 
The emphasis on data-driven activism as opposed to "playing politics," is a recurring theme for many physicians who publicly engage with social issues. 
"It's not partisan," Dr. Ranney said. "Rather, it's a commitment to translating science into actionable steps that can be used regardless of what political party you are in. My job is not to be on one side or the other, but to advance human health." These doctors challenge their critics to explain how such a goal is outside their purview. 
A version of this article first appeared on Medscape.com.

It should come as no surprise that when physicians speak out on social and political issues, there is sometimes a backlash. This can range from the typical trolling that occurs online to rarer cases of professional penalties. Two doctors were fired by NYU Langone Health late last year after they posted social media messages about the Israel-Hamas war. Still, many physicians are not only willing to stand up for what they believe in, but they see it as an essential part of their profession. 
"We're now at a place where doctors need to engage in public advocacy as an urgent part of our job," wrote Rob Davidson, MD, an emergency department physician, at the onslaught of the COVID-19 pandemic. In an Op-Ed piece for The Guardian, Dr. Davidson noted how the virus forced many physicians into becoming "activist doctors," calling for adequate personal protective equipment and correcting misinformation. "What we want above all is for the administration to listen to doctors, nurses, and frontline health workers - and stop playing politics," he wrote. 

'It's Not About Being Political' 

The intersection of medicine and politics is hardly new. Doctors frequently testify before Congress, sharing their expertise on issues concerning public health. This, however, isn't the same as "playing politics." 
"I'm not taking political stances," said Megan Ranney, MD, Dean of the Yale School of Public Health. "Rather, I'm using science to inform best practices, and I'm vocal around the area where I have expertise where we could do collectively better." 
Dr. Ranney's work to end firearm injury and death garnered particular attention when she co-authored an open letter to the National Rifle Association (NRA) in 2018. She wrote the letter in response to a tweet by the organization, admonishing physicians to "stay in their lane" when it comes to gun control.  
Dr. Ranney's letter discussed gun violence as a public health crisis and urged the NRA to "be part of the solution" by joining the collective effort to reduce firearm injury and death through research, education, and advocacy. "We are not anti-gun," she stated. "We are anti-bullet hole," adding that "almost half of doctors own guns." 
The NRA disagreed. When Dr. Ranney testified before Congress during a hearing on gun violence in 2023, NRA spokesperson Billy McLaughlin condemned her testimony as an effort to "dismantle the Second Amendment," calling Dr. Ranney "a known gun control extremist." 
"If you actually read what I write, or if you actually listen to what I say, I'm not saying things on behalf of one political party or another," said Dr. Ranney. "It's not about being political. It's about recognizing our role in describing what's happening and making it clear for the world to see. Showing where, based off of data, there may be a better path to improve health and wellbeing." 
In spite of the backlash, Dr. Ranney has no regrets about being an activist. "In the current media landscape, folks love to slap labels on people that may or may not be accurate. To me, what matters isn't where I land with a particular politician or political party, but how the work that I do improves health for populations." 

When the Need to Act Outweighs the Fear 

Laura Andreson, DO, an ob.gyn, took activism a step further when she joined a group of women in Tennessee to file a suit against the state, the attorney general, and the state board of medical examiners. The issue was the Tennessee's abortion ban, which the suit claimed prevented women from getting "necessary and potentially life-saving medical care."  
Dr. Andreson, who says she was "not at all" politically active in the past, began to realize how the abortion ban could drastically affect her profession and her patients. "I don't know what flipped in me, but I just felt like I could do this," she said. 
Like Dr. Ranney, Dr. Andreson has been as visible as she has been vocal, giving press conferences and interviews, but she acknowledges she has some fears about safety. In fact, after filing the lawsuit, the Center for Reproductive Rights recommended that she go to a website, DeleteMe, that removes personal data from the internet, making it more difficult for people to find her information. "But my need to do this and my desire to do this is stronger than my fears," she added. 
Dr. Andreson, who is part of a small practice, did check with both her coworkers and the hospital administration before moving forward with the lawsuit. She was relieved to find that she had the support of her practice and that there wasn't anything in the hospital bylaws to prevent her from filing the lawsuit. "But the people in the bigger institutions who probably have an even better expert base than I do, they are handcuffed," she said. 
It has been, in Dr. Andreson's words, "a little uncomfortable" being on the board of the Tennessee Medical Association when the Tennessee Board of Medical Examiners is part of the lawsuit. "We're all members of the same group," she said. "But I'm not suing them as individuals; I'm suing them as an entity that is under our government." 
Dr. Andreson said most people have been supportive of her activist work, though she admitted to feeling frustrated when she encounters apathy from fellow ob.gyns. She got little response when she circulated information explaining the abortion laws and trying to get others involved. But she still sees education as being a key part of making change happen.  
"I think advocacy, as someone who is considered a responsible, trustworthy person by your community, is important, because you can sway some people just by educating them," she said. 

Fighting Inequities in Medicine and Beyond 

Christina Chen, MD, says she felt very supported by her medical community at the Mayo Clinic in Rochester, Minnesota, when she and 16 other Asian American physicians posted a video on Instagram in 2020 highlighting increased violence and harassment of Asian Americans during COVID-19. It soon went viral, and the Mayo Clinic distributed it across their social media channels. The only negative repercussions Mayo faced were a few posts on social media saying that politics should not be brought into the healthcare space. Dr. Chen disagrees. 
"Social issues and political decisions have direct impact on the health of our communities," Dr. Chen said. "We know that we still have a long way to go to solve health inequities, which is a public health problem, and we all play a huge role in voicing our concerns." 
Activism, however, seems to be more complicated when it involves physicians being critical of inequities within the medical field. Nephrologist, Vanessa Grubbs, MD, MPH, founded the nonprofit Black Doc Village in 2022 to raise awareness about the wrongful dismissal of Black residents and expand the Black physician workforce. 
Dr. Grubbs said that the medical community has not been supportive of her activism. "The reason why I'm no longer in academia is in part because they got very upset with me tweeting about how some trainees are biased in their treatment of attendings," she said. "Senior White men attendings are often treated very differently than junior women of color faculty." 
Dr. Grubbs also expressed her views in 2020 essay in the New England Journal of Medicine where she criticized academic medical institutions for ignoring systemic racism, paying lip service to diversity, equity, and inclusion, and staying "deafeningly silent" when issues of racism are raised. 
Today, Black Doc Village is focused on conducting research that can be used to change policy. And Dr. Grubbs now has the full support of her colleagues at West Oakland Health, in Oakland, California, which aspires to advance the Bay Area Black community's health and dignity. "So, no one here has a problem with me speaking out," she added. 
The emphasis on data-driven activism as opposed to "playing politics," is a recurring theme for many physicians who publicly engage with social issues. 
"It's not partisan," Dr. Ranney said. "Rather, it's a commitment to translating science into actionable steps that can be used regardless of what political party you are in. My job is not to be on one side or the other, but to advance human health." These doctors challenge their critics to explain how such a goal is outside their purview. 
A version of this article first appeared on Medscape.com.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Using ImPrint, an immune-related biomarker, clinicians can identify patients with breast cancer who are likely to respond to neoadjuvant immunotherapy, according to data from the ongoing phase 2 I-SPY2 trial.

Patient selection based on ImPrint class can result in high response rates and spare nonresponders the toxicities of immunotherapy, said Denise M. Wolf, PhD, during her presentation of the study results at the annual meeting of the American Association for Cancer Research (AACR).

“Our results show that patients with ER+/HER2-/ImPrint+ breast cancer have a very high probability of achieving complete response to immunotherapy, whereas those who are ER+/HER2-/ImPrint- have a low probability of responding,” noted Dr. Wolf, PhD, MSc of the University of California, San Francisco (UCSF), in an interview.

She added that, although effective, immunotherapy also carries the risk of serious immune-related toxicities, and knowledge of ImPrint class can help patients and physicians determine whether immunotherapy is a good treatment option. “Many patients will be willing to take the risk of immunotherapy toxicities if their odds of responding are very high, as is the case for ImPrint+ patients, but [are] likely less enthused with a low likelihood of response,” Dr. Wolf said during the interview.
 

Need for Predictive Biomarkers for Neoadjuvant Immunotherapy

Although neoadjuvant immunotherapy has become the standard treatment for patients with early-stage triple-negative breast cancer (TNBC), chemotherapy remains the mainstay of treatment for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. The I-SPY2 clinical trial is the first randomized clinical study to assess the efficacy of immunotherapy in the high-risk population of patients with HR+/HER2-, Dr. Wolf said. Data from this study suggest that a subset of HR+/HER2- patients may also derive substantial benefit from this approach compared with standard chemotherapy.

“We and others have previously observed that a minority of ER+/HER2- breast cancers are enriched for tumor-infiltrating lymphocytes and that high levels of immune-related gene signatures associate with improved survival in this subtype, as well as in TNBC,” noted Dr. Wolf during an interview.

She explained that patients with high-risk ER+/HER2- breast cancer were not responding to any of the experimental agent classes tested in the trial and showed particularly poor outcomes, and that she and her colleagues “wanted to see if immune-oncology agents would impact response in these patients.”
 

ImPrint, an Immune Expression Signature

Preliminary data from the I-SPY2 trial showed that immune-related gene signatures were associated with pathologic complete response (pCR) in patients with HR+/HER2- breast cancer treated with immunotherapy. This observation allowed investigators to develop a clinically applicable immune classifier, termed ImPrint, to predict response to immunotherapy in this population.

This immune classifier is a 53-gene signature developed using data from the first anti–programmed death-1 (PD-1) arm that included patients treated with pembrolizumab, explained Dr. Wolf.
 

Performance of ImPrint in Patients With HR+/HER2- Breast Cancer

Dr. Wolf presented new data on the performance of ImPrint in 204 patients with high-risk HR+/HER2- breast cancer from the following five immunotherapy arms of the I-SPY2 trial, at the meeting. These arms included: anti–PD-1, anti–PDL-1 plus PARP inhibitor, anti–PD-1/TLR9 dual immunotherapy, and anti–PD-1 with or without LAG3 inhibitor. Data from 191 patients treated with the current standard of care (paclitaxel followed by adriamycin and cyclophosphamide cytoxan) were included in the analysis as a control.

The pCR in the entire population across these five immunotherapy arms was 33%. The response rate in the control arm was 13.5%.

“The high pCR in the immunotherapy groups is remarkable given the traditionally poor response of HR+/HER2- tumors to standard neoadjuvant chemotherapy,” said Ritu Aneja, PhD, the associate dean for research and innovation at the University of Alabama at Birmingham and a breast cancer expert, who was not involved in the I-SPY2 trial.

When patients were stratified according to ImPrint status, significant differences were observed among the groups. In this analysis, 28% of HR+/HER2- patients were classified as ImPrint positive (likely sensitive) based on ImPrint expression levels in pretreatment mRNA samples, and these individuals achieved pCR rates as high as 76% with immunotherapy.

In comparison, pCR rates were only 16% in ImPrint-negative (likely resistant) patients. The highest response rate was observed in the anti–PD-1/TLR9 dual immunotherapy arm, with a pCR rate of greater than 90% in ImPrint-positive patients. In the control arm, pCR rates were 33% in ImPrint-positive and 8% in ImPrint-negative patients.

“These results suggest that a subset of [patients with] high-risk HR+/HER2- breast cancers is highly sensitive to immunotherapy,” said Dr. Aneja in an interview. “By using a specific and sensitive selection strategy like ImPrint, we may be able to identify patients who can achieve pCR rates similar to what we see with the best neoadjuvant therapies in triple-negative and HER2-positive disease.”
 

Ability of ImPrint to Predict Long-Term Outcomes

During her talk, Dr. Wolf explained that she and her research team currently do not have sufficient follow-up data to assess the ability of ImPrint to predict long-term outcomes. Therefore, they used the pCR data to predict long-term disease-free survival (DRFS) outcomes. Based on their model, HR+/HER2-/ImPrint+ patients treated with immunotherapy were estimated to have a 91% 5-year DRFS rate, compared with 80% for those receiving standard chemotherapy alone. This represents a 52% reduction in the risk of disease recurrence.

“This suggests not only a higher immediate response rate to therapy but also potential long-term benefits for patients identified as ImPrint+,” Dr. Aneja said, commenting on the significance of the DRFS data, during the interview, She added that the ability to predict longer-term outcomes is a critical advantage in selecting the most effective treatment strategies for patients.
 

Comparison of ImPrint With Other Biomarkers

The investigators compared ImPrint to other potential biomarkers for immunotherapy response, including MammaPrint (ultra) High2 risk (MP2) and tumor grade. During her talk, Dr. Wolf showed data demonstrating that ImPrint is a more precise predictor of pCR, with higher response rates than either of those other markers.

The pCR rates for MP2 and grade III were 56% and 45%, respectively, which are much smaller than the pCR rates observed for ImPrint+ patients (75%).

“This difference underscores ImPrint’s effectiveness in distinguishing patients who could benefit from immunotherapy, offering a pCR prediction accuracy that is significantly higher than seen with other biomarkers that have been proposed as selection markers for neoadjuvant immunotherapy trials in HR+/HER2- breast cancers, such as MP2 and tumor grade,” said Dr. Aneja, during the interview.
 

Looking Ahead — Implementation of Imprint for Patient Selection

Dr. Aneja echoed that the findings from the I-SPY2 trial advocate for the integration of biomarker-driven approaches, particularly the use of the ImPrint classifier, into the treatment planning process for high-risk HR+/HER2- breast cancer.

“This approach can enable clinicians to identify patients who are more likely to benefit from immunotherapy, thus personalizing treatment strategies and potentially enhancing treatment efficacy while minimizing exposure to unnecessary toxicity for those unlikely to respond,” she said.

Dr. Aneja added that while the I-SPY2 trial offers promising data on ImPrint’s efficacy, additional prospective studies are needed to validate these findings across diverse patient populations and settings, as well as the correlation between biomarker positivity and long-term clinical outcomes, including DRFS and overall survival. “This will help to better understand the full spectrum of benefits provided by immunotherapies in biomarker-selected patient groups,” she said.

Dr. Wolf and Dr. Aneja reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of fam-trastuzumab–deruxtecan-nxki (Enhertu; AstraZeneca and Daiichi Sankyo, Inc) to adults with unresectable or metastatic HER2-positive solid tumors who have no satisfactory alternative after prior systemic treatment.

The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.

The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.

“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.

Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.

The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.

Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity. 

The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of fam-trastuzumab–deruxtecan-nxki (Enhertu; AstraZeneca and Daiichi Sankyo, Inc) to adults with unresectable or metastatic HER2-positive solid tumors who have no satisfactory alternative after prior systemic treatment.

The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.

The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.

“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.

Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.

The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.

Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity. 

The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of fam-trastuzumab–deruxtecan-nxki (Enhertu; AstraZeneca and Daiichi Sankyo, Inc) to adults with unresectable or metastatic HER2-positive solid tumors who have no satisfactory alternative after prior systemic treatment.

The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.

The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.

“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.

Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.

The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.

Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity. 

The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
 

A version of this article appeared on Medscape.com.

Premenstrual disorders (PMDs) and perinatal depression (PND) appear to have a bidirectional association, a Swedish national registry-based analysis found.

In women with PND, 2.9% had PMDs before pregnancy vs 0.6% in a matched cohort of unaffected women, according to an international team led by Quian Yang, MD, PhD, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, Sweden. Their study appears in PLoS Medicine.

“Preconception and maternity care providers should be aware of the risk of developing perinatal depression among women with a history of PMDs,” Dr. Yang said in an interview. “Healthcare providers may inform women with perinatal depression about the potential risk of PMDs when menstruation returns after childbirth.” She recommended screening as part of routine perinatal care to identify and treat the condition at an early stage. Counseling and medication may help prevent adverse consequences.

In other findings, the correlation with PMDs held for both prenatal and postnatal depression, regardless of any history of psychiatric disorders and also in full-sister comparisons, the authors noted, with a stronger correlation in the absence of psychiatric disorders (P for interaction <.001).

“Interestingly, we noted a stronger association between PMDs and subsequent PND than the association in the other direction, Dr. Yang said. And although many experience PMD symptom onset in adolescence, symptom worsening has been reported with increasing age and parity. “It is possible that women with milder premenstrual symptoms experienced worse symptoms after pregnancy and are therefore first diagnosed with PMD after pregnancy,” the authors hypothesized.

Both PMDs and PND share depressive symptomatology and onset coinciding with hormonal fluctuations, particularly estrogen and progesterone, suggesting a shared etiology, Dr. Yang explained. “It’s plausible that an abnormal response to natural hormone fluctuations predisposes women to both PMDs and PND. However, the underlying mechanism is complex, and future research is needed to reveal the underlying etiology.”

Affecting a majority of women of reproductive age to some degree, PMDs in certain women can cause significant functional impairment and, when severe, have been linked to increased risks of accidents and suicidal behavior. The psychological symptoms of the more serious form, premenstrual dysphoric disorder, for example, are associated with a 50%-78% lifetime risk for psychiatric disorders, including major depressive, dysthymic, seasonal affective, and generalized anxiety disorders, as well as suicidality.

Mood disorders are common in pregnancy and the postpartum period.

The Swedish Study

In 1.8 million singleton pregnancies in Sweden during 2001-2018, the investigators identified 84,949 women with PND and 849,482 unaffected women and individually matched them 10:1 by age and calendar year. Incident PND and PMDs were identified through clinical diagnoses or prescribed medications, and adjustment was made for such demographics as country of birth, educational level, region of residency, and cohabitation status.

In an initial matched-cohort case-control study with a mean follow-up of 6.9 years, PMDs were associated with a nearly five times higher risk of subsequent PND (odds ratio, 4.76; 95% CI, 4.52-5.01; P <.001).

In another matched cohort with a mean follow-up of 7.0 years, there were 4227 newly diagnosed PMDs in women with PND (incidence rate [IR], 7.6/1000 person-years) and 21,326 among controls (IR, 3.8/1000). Compared with matched controls, women with PND were at almost twice the risk of subsequent PMDs (hazard ratio, 1.81; 95% CI, 1.74-1.88; P <.001).

Commenting on the study but not involved in it, Bernard L. Harlow, PhD, a professor of epidemiology at Boston University School of Public Health in Massachusetts who specializes in epidemiologic studies of female reproductive disorders, said he was not surprised at these findings, which clearly support the need for PMD screening in mothers-to-be. “Anything that is easy to measure and noninvasive that will minimize the risk of postpartum depression should be part of the standard of care during the prenatal period.” As to safety: If treatment is indicated, he added, “studies have shown that the risk to the mother and child is much greater if the mother’s mood disorder is not controlled than any risk to the baby due to depression treatment.” But though PMDs may be predictive of PND, there are still barriers to actual PND care. A 2023 analysis reported that 65% of mothers-to-be who screened positive for metal health comorbidities were not referred for treatment.

Dr. Yang and colleagues acknowledged that their findings may not be generalizable to mild forms of these disorders since the data were based on clinical diagnoses and prescriptions.

The study was supported by the Chinese Scholarship Council, the Swedish Research Council for Health, Working Life and Welfare, the Karolinska Institutet, and the Icelandic Research Fund. The authors and Dr. Harlow had no relevant competing interests to disclose.

Premenstrual disorders (PMDs) and perinatal depression (PND) appear to have a bidirectional association, a Swedish national registry-based analysis found.

In women with PND, 2.9% had PMDs before pregnancy vs 0.6% in a matched cohort of unaffected women, according to an international team led by Quian Yang, MD, PhD, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, Sweden. Their study appears in PLoS Medicine.

“Preconception and maternity care providers should be aware of the risk of developing perinatal depression among women with a history of PMDs,” Dr. Yang said in an interview. “Healthcare providers may inform women with perinatal depression about the potential risk of PMDs when menstruation returns after childbirth.” She recommended screening as part of routine perinatal care to identify and treat the condition at an early stage. Counseling and medication may help prevent adverse consequences.

In other findings, the correlation with PMDs held for both prenatal and postnatal depression, regardless of any history of psychiatric disorders and also in full-sister comparisons, the authors noted, with a stronger correlation in the absence of psychiatric disorders (P for interaction <.001).

“Interestingly, we noted a stronger association between PMDs and subsequent PND than the association in the other direction, Dr. Yang said. And although many experience PMD symptom onset in adolescence, symptom worsening has been reported with increasing age and parity. “It is possible that women with milder premenstrual symptoms experienced worse symptoms after pregnancy and are therefore first diagnosed with PMD after pregnancy,” the authors hypothesized.

Both PMDs and PND share depressive symptomatology and onset coinciding with hormonal fluctuations, particularly estrogen and progesterone, suggesting a shared etiology, Dr. Yang explained. “It’s plausible that an abnormal response to natural hormone fluctuations predisposes women to both PMDs and PND. However, the underlying mechanism is complex, and future research is needed to reveal the underlying etiology.”

Affecting a majority of women of reproductive age to some degree, PMDs in certain women can cause significant functional impairment and, when severe, have been linked to increased risks of accidents and suicidal behavior. The psychological symptoms of the more serious form, premenstrual dysphoric disorder, for example, are associated with a 50%-78% lifetime risk for psychiatric disorders, including major depressive, dysthymic, seasonal affective, and generalized anxiety disorders, as well as suicidality.

Mood disorders are common in pregnancy and the postpartum period.

The Swedish Study

In 1.8 million singleton pregnancies in Sweden during 2001-2018, the investigators identified 84,949 women with PND and 849,482 unaffected women and individually matched them 10:1 by age and calendar year. Incident PND and PMDs were identified through clinical diagnoses or prescribed medications, and adjustment was made for such demographics as country of birth, educational level, region of residency, and cohabitation status.

In an initial matched-cohort case-control study with a mean follow-up of 6.9 years, PMDs were associated with a nearly five times higher risk of subsequent PND (odds ratio, 4.76; 95% CI, 4.52-5.01; P <.001).

In another matched cohort with a mean follow-up of 7.0 years, there were 4227 newly diagnosed PMDs in women with PND (incidence rate [IR], 7.6/1000 person-years) and 21,326 among controls (IR, 3.8/1000). Compared with matched controls, women with PND were at almost twice the risk of subsequent PMDs (hazard ratio, 1.81; 95% CI, 1.74-1.88; P <.001).

Commenting on the study but not involved in it, Bernard L. Harlow, PhD, a professor of epidemiology at Boston University School of Public Health in Massachusetts who specializes in epidemiologic studies of female reproductive disorders, said he was not surprised at these findings, which clearly support the need for PMD screening in mothers-to-be. “Anything that is easy to measure and noninvasive that will minimize the risk of postpartum depression should be part of the standard of care during the prenatal period.” As to safety: If treatment is indicated, he added, “studies have shown that the risk to the mother and child is much greater if the mother’s mood disorder is not controlled than any risk to the baby due to depression treatment.” But though PMDs may be predictive of PND, there are still barriers to actual PND care. A 2023 analysis reported that 65% of mothers-to-be who screened positive for metal health comorbidities were not referred for treatment.

Dr. Yang and colleagues acknowledged that their findings may not be generalizable to mild forms of these disorders since the data were based on clinical diagnoses and prescriptions.

The study was supported by the Chinese Scholarship Council, the Swedish Research Council for Health, Working Life and Welfare, the Karolinska Institutet, and the Icelandic Research Fund. The authors and Dr. Harlow had no relevant competing interests to disclose.

Premenstrual disorders (PMDs) and perinatal depression (PND) appear to have a bidirectional association, a Swedish national registry-based analysis found.

In women with PND, 2.9% had PMDs before pregnancy vs 0.6% in a matched cohort of unaffected women, according to an international team led by Quian Yang, MD, PhD, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, Sweden. Their study appears in PLoS Medicine.

“Preconception and maternity care providers should be aware of the risk of developing perinatal depression among women with a history of PMDs,” Dr. Yang said in an interview. “Healthcare providers may inform women with perinatal depression about the potential risk of PMDs when menstruation returns after childbirth.” She recommended screening as part of routine perinatal care to identify and treat the condition at an early stage. Counseling and medication may help prevent adverse consequences.

In other findings, the correlation with PMDs held for both prenatal and postnatal depression, regardless of any history of psychiatric disorders and also in full-sister comparisons, the authors noted, with a stronger correlation in the absence of psychiatric disorders (P for interaction <.001).

“Interestingly, we noted a stronger association between PMDs and subsequent PND than the association in the other direction, Dr. Yang said. And although many experience PMD symptom onset in adolescence, symptom worsening has been reported with increasing age and parity. “It is possible that women with milder premenstrual symptoms experienced worse symptoms after pregnancy and are therefore first diagnosed with PMD after pregnancy,” the authors hypothesized.

Both PMDs and PND share depressive symptomatology and onset coinciding with hormonal fluctuations, particularly estrogen and progesterone, suggesting a shared etiology, Dr. Yang explained. “It’s plausible that an abnormal response to natural hormone fluctuations predisposes women to both PMDs and PND. However, the underlying mechanism is complex, and future research is needed to reveal the underlying etiology.”

Affecting a majority of women of reproductive age to some degree, PMDs in certain women can cause significant functional impairment and, when severe, have been linked to increased risks of accidents and suicidal behavior. The psychological symptoms of the more serious form, premenstrual dysphoric disorder, for example, are associated with a 50%-78% lifetime risk for psychiatric disorders, including major depressive, dysthymic, seasonal affective, and generalized anxiety disorders, as well as suicidality.

Mood disorders are common in pregnancy and the postpartum period.

The Swedish Study

In 1.8 million singleton pregnancies in Sweden during 2001-2018, the investigators identified 84,949 women with PND and 849,482 unaffected women and individually matched them 10:1 by age and calendar year. Incident PND and PMDs were identified through clinical diagnoses or prescribed medications, and adjustment was made for such demographics as country of birth, educational level, region of residency, and cohabitation status.

In an initial matched-cohort case-control study with a mean follow-up of 6.9 years, PMDs were associated with a nearly five times higher risk of subsequent PND (odds ratio, 4.76; 95% CI, 4.52-5.01; P <.001).

In another matched cohort with a mean follow-up of 7.0 years, there were 4227 newly diagnosed PMDs in women with PND (incidence rate [IR], 7.6/1000 person-years) and 21,326 among controls (IR, 3.8/1000). Compared with matched controls, women with PND were at almost twice the risk of subsequent PMDs (hazard ratio, 1.81; 95% CI, 1.74-1.88; P <.001).

Commenting on the study but not involved in it, Bernard L. Harlow, PhD, a professor of epidemiology at Boston University School of Public Health in Massachusetts who specializes in epidemiologic studies of female reproductive disorders, said he was not surprised at these findings, which clearly support the need for PMD screening in mothers-to-be. “Anything that is easy to measure and noninvasive that will minimize the risk of postpartum depression should be part of the standard of care during the prenatal period.” As to safety: If treatment is indicated, he added, “studies have shown that the risk to the mother and child is much greater if the mother’s mood disorder is not controlled than any risk to the baby due to depression treatment.” But though PMDs may be predictive of PND, there are still barriers to actual PND care. A 2023 analysis reported that 65% of mothers-to-be who screened positive for metal health comorbidities were not referred for treatment.

Dr. Yang and colleagues acknowledged that their findings may not be generalizable to mild forms of these disorders since the data were based on clinical diagnoses and prescriptions.

The study was supported by the Chinese Scholarship Council, the Swedish Research Council for Health, Working Life and Welfare, the Karolinska Institutet, and the Icelandic Research Fund. The authors and Dr. Harlow had no relevant competing interests to disclose.

Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.

Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).

Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.

The Study

In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.

Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.

Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.

On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.

A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.

These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.

Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.

The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.

Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.

Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).

Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.

The Study

In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.

Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.

Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.

On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.

A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.

These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.

Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.

The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.

Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.

Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).

Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.

The Study

In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.

Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.

Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.

On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.

A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.

These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.

Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.

The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.