Ob.Gyn. News

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

CHICAGO — Being hormone receptor positive is generally a favorable prognostic factor in breast cancer, but that doesn’t seem to be the case in women with BRCA-associated tumors, according to a study presented at the American Society of Clinical Oncology annual meeting.

The conclusion is based on a large international study on how hormone receptor status impacts breast cancer outcomes in young women with germline BRCA pathological variants (PVs).

Overall, “hormone receptor positivity did not seem to have a strong positive prognostic value in young BRCA carriers” with early breast cancer, lead investigator Luca Arecco, MD, an oncology resident at the University of Genoa, Italy, said at the meeting.

Investigators reviewed the records of 4709 women ages 40 years or younger with stage 1-3 BRCA-associated invasive breast cancer treated from 2000 to 2020 at 78 centers in 28 countries across four continents. Median follow-up was about 8 years.
 

Weaker Prognostic Value in Hormone Receptor Status

They found, in general, that hormone receptor–positive breast cancer appears to be biologically more aggressive in patients with BRCA PVs than in the general breast cancer population, generating outcomes similar to those with hormone receptor-negative BRCA tumors.

Specifically, among patients with germline BRCA PVs, while hormone receptor–positive patients had a higher distant recurrence rate (13.1% vs. 9.6%) than hormone receptor–negative patients, 8-year disease free survival (65.8% and 63.4% respectively) and overall survival (a bit under 90% in both groups) were similar.

Hormone receptor–positive patients did have a lower rate of second primary breast cancers (9.1% versus 14.7%).

In the formal write-up of the results published shortly after the meeting in Annals of Oncology, the investigators concluded that “in young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor–positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.”

The team also found other differences between BRCA-associated breast cancer and sporadic disease. For instance, in the BRCA cohort, luminal A-like breast cancer had a worse long-term prognosis in their BRCA cohort than triple-negative or HER2-positive disease. Luminal A-like tumors are generally considered less aggressive, but in patients with BRCA PVs, “improving neoadjuvant chemotherapy … could be worthwhile,” the investigators said.

Also, although the risk of recurrence for sporadic hormone receptor–negative tumors is highest in the first few years, the team found that the risk in the hormone negative BRCA cohort progressively increased with longer follow-up, driven by the occurrence of second primary breast cancers, especially in patients with BRCA 1 PVs.
 

Greater Clarity in Prognosis in BRCA-Associated Breast Cancer

Overall, study discussant Lisa A. Carey, MD, a breast cancer specialist at the University of North Carolina at Chapel Hill, said, “we now know much more clearly the issues of prognosis in women who are very young and have germline BRCA-associated breast cancer,” about 12% of newly diagnosed cases.

“Young patients with germline BRCA-associated breast cancers have high relapse and high new primary risks, warranting comprehensive multimodality therapy,” she said.

A bit fewer than half of women in the study were hormone receptor–positive, and they tended to be patients with BRCA 2 PVs. The rest were hormone receptor–negative and tended to have BRCA 1 PVs.

Patients with hormone receptor–positive disease had grade 3 cancers in about 50% of cases, while patients with hormone receptor–negative disease had a grade 3 disease in over 80%.

Hormone receptor–positive patients were more likely to have nodal involvement and undergo mastectomies but less likely to receive chemotherapy than hormone receptor–negative patients. It’s likely that few patients in the review received PARP inhibitors, Dr. Carey noted.

Although overall survival at 8 years was similar in both groups, after that point “the prognosis of patients with hormone receptor–positive disease appeared to be worse … This appeared to occur earlier than that described in sporadic disease,” in which the worsening of survival in hormone receptor–positive disease occurs after a follow-up of at least 14-15 years, the investigators noted in their journal report.

The work was funded by the Italian Association for Cancer Research, Institut Jules Bordet, Korea Health Industry Development Institute, Australian National Health and Medical Council, Cancer Australia, US National Institute of Health, and others. Dr. Arecco had no disclosures. Dr. Carey and other coauthors disclosed research funding, speaker honoraria, and other financial relationships with AstraZeneca, Genentech/Roche, Lilly, and other pharmaceutical companies.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Black metastatic breast cancer patients with PIK3CA mutations were less likely to receive targeted therapy and less likely to be enrolled in clinical trials than White patients and had shorter overall survival, according to a retrospective cohort study. Black and White patients were equally likely to receive other drugs that did not require genomic testing.

“These clinical inequities in the use of targeted therapies and clinical trials ... must be a focus going forward,” said lead investigator Emily Podany, MD, a clinical fellow in hematology-oncology at Washington University in St. Louis, Missouri. “Our consortium is looking for paths forward in order to try and decrease these striking inequities. And it’s a focus of future research for us and future implementation [of] science interventions, hopefully, across the country.”

The study results were presented at the annual meeting of the American Society of Clinical Oncology.
 

Black Women Underrepresented

Black women are generally underrepresented in clinical trials, noted Dr. Podany. “They make up about 2%-5% of the patients in breast cancer clinical trials, and there are documented inequities in treatment and in outcomes for Black patients with metastatic breast cancer. This includes longer treatment delays, it includes fewer sentinel lymph node biopsies, and unfortunately, they’re more likely to discontinue treatment early.”

In terms of PI3K inhibition, PIK3CA mutations are found in about 40% of patients with HR-positive HER2-negative metastatic breast cancer. Alpelisib is FDA-approved as a targeted therapy for these patients, she said.

The study evaluated records of 1327 patients with metastatic breast cancer who also had circulating tumor DNA (ctDNA) results and were treated at Washington University, Massachusetts General Hospital in Boston, and Northwestern University in Chicago. Of these, 795 had an ER-positive, HER2-negative subtype and were included in the analysis. Most (89%) of the patients were White (n = 708), while 11% (n = 87) were Black, and the only baseline difference between patients was that Black patients had significantly more de novo metastatic breast cancer (31% versus 22%).

Use of PI3K, CDK4/6, or mTOR inhibitors was evaluated using manual electronic medical review, and genomic differences were evaluated using logistic regression.

The analysis showed inequities in both treatment and clinical trial enrollment. There were no differences between groups in the use of CDK4/6 or mTOR inhibitors, which do not require a genomic profile, the researchers noted, but Black patients with PIK3CA single nucleotide variants (SNV) were significantly less likely than White patients to use PI3K inhibitors (5.9% versus 28.8%; P = .045), despite no difference in PIK3CA mutations between groups (36% and 34% respectively). Similarly, 11% of White patients with PIK3CA mutations were enrolled in clinical trials, but none of the Black patients was.

Genomic differences were also found, Dr. Podany reported. Black patients with estrogen/progesterone receptor (ER/PR) positive, HER2-negative disease were more likely to have a CCND1 copy number variant. And for ER-positive PR-negative HER2-negative patients, Black patients were more likely to have a GATA3 SNV, while White patients were more likely to have a KRAS copy number variant.
 

Black Survival Less Than Half

The analysis also found significant differences in overall survival from the time of the first liquid biopsy, with White ER-positive, PR-negative, HER2-negative patients living a median of 21 months, versus 9.1 months for Black patients.

There were several limitations to the study beyond its retrospective nature, “so, we may be underestimating the true inequity,” noted Dr. Podany. “These are large urban academic centers, so our patients have access to these treatments. They have access to care. They have access to ctDNA liquid biopsy testing. And the timing of ctDNA, especially the first ctDNA test, is variable and provider-dependant. We were also unable to assess receipt of PI3 kinase inhibitors at future time points after the end of this cohort study.”

Asked for comment, Giuseppe Del Priore, MD, MPH, from Morehouse School of Medicine in Atlanta, Georgia, approved of the study design “with subjects limited to three distinctive institutions. That parameter alone can control for several unknown variables among the studied comparison groups, ie, Black women versus others.”

However, Dr. Del Priore, who is adjunct professor of obstetrics and gynecology, with a specialty in oncology, added, “retrospective studies are not reliable except for generating hypotheses. Therefore, I would like to see a rapid implementation of an intervention trial at these same institutions to ensure equal consideration of, and access to, targeted therapies. Too often a retrospective correlation is reported, but the solution is elusive due to unknown factors. In this case, knowing there is a mutation is far from alleviating the disproportionate burden of disease that many communities face.”

Dr. Podany had no relevant disclosures. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

Twice-yearly injections are 100% effective in preventing new infections, according to the final results from the PURPOSE 1 trial of lenacapavir.

For weeks, the HIV community has been talking about this highly anticipated clinical trial and whether the strong — and to many, surprising — interim results would hold at final presentation at the International AIDS Conference 2024 in Munich, Germany.

Presenting the results, Linda-Gail Bekker, MD, director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, reported zero new infections in those who got the shots in the study of about 5000 young women. In the group given daily oral preexposure prophylaxis (PrEP), roughly 2% contracted HIV from infected partners.

“A twice-yearly PrEP choice could overcome some of the adherence and persistence challenges and contribute critically to our quest to reduce HIV infection in women around the world,” Dr. Bekker said about the results, which were published simultaneously in The New England Journal of Medicine.

PURPOSE 1 confirmed that lenacapavir is a “breakthrough” for HIV prevention, said International AIDS Society president Sharon Lewin, PhD, MBBS. It has “huge public health potential,” said Dr. Lewin, the AIDS 2024 conference cochair and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

Lenacapavir is a novel, first-in-class multistage HIV-1 capsid inhibitor with a long half-life, which enables the twice-yearly dosing.

PURPOSE 1 enrolled women aged 15-25 years who were at risk for HIV in South Africa and Uganda, with a primary endpoint of HIV infection. Because of the previously announced interim results, which showed the injection was preventing infections, study sponsor Gilead Sciences discontinued the randomized phase of the trial and shifted to an open-label design for lenacapavir.

“One hundred percent efficacy is more that we could ever have hoped for a potential prevention efficacy,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich and AIDS 2024 conference cochair.

Dr. Spinner added that while this is the first study of lenacapavir for PrEP, it’s also the first to explore outcomes of emtricitabine-tenofovir in cisgender women.
 

Strong Adherence Rates

The twice-yearly injection demonstrated adherence rates above 90% in the trial for both the 6- and 12-month injection intervals.

“Adherence was 91.5% at week 26 and 92.8% at week 52,” Dr. Bekker reported. 

The trial compared three PrEP options including the lenacapavir injection to once-daily oral emtricitabine 200 mg and tenofovir-alafenamide 25 mg (F/TAF) and once-daily emtricitabine 200 mg and tenofovir–disoproxil fumarate 300 mg (F/TDF).

“Most participants in both the F/TAF and F/TDF groups had low adherence, and this declined over time,” Dr. Bekker reported. At 52 weeks, the vast majority of patients on both oral therapies had low adherence with dosing, defined at less than two doses a week.

Dr. Bekker called the adherence to the oral agents in this trial “disappointing.”

Findings from the trial underscore the challenges of adherence to a daily oral medication, Rochelle Walensky, MD, and Lindsey Baden, MD, from the Harvard Kennedy School of Government and Harvard Business School in Cambridge, Massachusetts, wrote in an editorial accompanying the published results.

With almost 92% attendance for the twice-yearly lenacapavir injections, the “well-done,” large, randomized, controlled trial “exemplifies not only that women can dependably adhere to this administration schedule, but also that levels of an HIV-1 capsid inhibitor can remain high enough over a period of 6 months to reliably prevent infection,” they added. 

Another key focus of the presentation was adverse events. The rate of adverse events grade 3 or more in the lenacapavir arm was 4.1%, Bekker said, which is slightly lower than the rates in the oral arms. The rates of serious adverse events were 2.8% for lenacapavir, 4% for F/TAF and 3.3% for F/TDF. 
 

Injection Site Reactions

Injection site reactions occurred in 68% of the lenacapavir group, including 63% with subcutaneous nodules.

The injection can form “a drug depot which may be palpable as a nodule,” Dr. Bekker said. In the placebo group, 34% of patients had injection-site reactions and 16% had nodules. Nearly all injection-site reactions were grade 1 or 2, she said. “Higher grade injection-site reactions were rare and not serious and occurred in a similar percentage in lenacapavir and placebo,” she said.

Overall, more than 25,000 injections of lenacapavir have been given, Dr. Bekker said, and four patients discontinued treatment because of injection-site reactions. “Reporting of injection-site reactions, including nodules, decreased with subsequent doses,” she said.

Contraception was not a requirement for enrollment in the study, Dr. Bekker pointed out, and pregnancy outcomes across the treatment arms were similar to the general population.
 

First in a Series of Trials

This is the first in a series of PURPOSE trials, Bekker reported. The phase 3 PURPOSE 2 trial, enrolling 3000 gay men, transgender women, transgender men and gender nonbinary people who have sex with male partners, is the second pivotal trial now underway.

Three other smaller trials are in the clinic in the United States and Europe.

PURPOSE 1 participants will continue to access lenacapavir until the product is available in South Africa and Uganda, Dr. Bekker said. Trial sponsor Gilead Sciences is also developing a direct licensing program to expedite generic access to the drug in high-incidence, resource-limited countries, she said.

Dr. Walensky and Dr. Baden report that lenacapavir currently costs about $43,000 annually in the United States. “But the results of the PURPOSE 1 trial have now created a moral imperative to make lenacapavir broadly accessible and affordable as PrEP” to people who were enrolled, as well as all those who are similarly eligible and could benefit.

So now we have a PrEP product with high efficacy, they added. “That is great news for science but not (yet) great for women.” 

Given the high pregnancy rate among participants in the PURPOSE 1 trial, Dr. Walensky and Dr. Baden point out the assessment of lenacapavir safety is a priority. They are also interested in learning more about drug resistance with this new option. 

“I f approved and delivered — rapidly, affordably, and equitably — to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention,” Dr. Lewin said.

Now, she added, “we eagerly await results from PURPOSE 2.”
 

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

Twice-yearly injections are 100% effective in preventing new infections, according to the final results from the PURPOSE 1 trial of lenacapavir.

For weeks, the HIV community has been talking about this highly anticipated clinical trial and whether the strong — and to many, surprising — interim results would hold at final presentation at the International AIDS Conference 2024 in Munich, Germany.

Presenting the results, Linda-Gail Bekker, MD, director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, reported zero new infections in those who got the shots in the study of about 5000 young women. In the group given daily oral preexposure prophylaxis (PrEP), roughly 2% contracted HIV from infected partners.

“A twice-yearly PrEP choice could overcome some of the adherence and persistence challenges and contribute critically to our quest to reduce HIV infection in women around the world,” Dr. Bekker said about the results, which were published simultaneously in The New England Journal of Medicine.

PURPOSE 1 confirmed that lenacapavir is a “breakthrough” for HIV prevention, said International AIDS Society president Sharon Lewin, PhD, MBBS. It has “huge public health potential,” said Dr. Lewin, the AIDS 2024 conference cochair and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

Lenacapavir is a novel, first-in-class multistage HIV-1 capsid inhibitor with a long half-life, which enables the twice-yearly dosing.

PURPOSE 1 enrolled women aged 15-25 years who were at risk for HIV in South Africa and Uganda, with a primary endpoint of HIV infection. Because of the previously announced interim results, which showed the injection was preventing infections, study sponsor Gilead Sciences discontinued the randomized phase of the trial and shifted to an open-label design for lenacapavir.

“One hundred percent efficacy is more that we could ever have hoped for a potential prevention efficacy,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich and AIDS 2024 conference cochair.

Dr. Spinner added that while this is the first study of lenacapavir for PrEP, it’s also the first to explore outcomes of emtricitabine-tenofovir in cisgender women.
 

Strong Adherence Rates

The twice-yearly injection demonstrated adherence rates above 90% in the trial for both the 6- and 12-month injection intervals.

“Adherence was 91.5% at week 26 and 92.8% at week 52,” Dr. Bekker reported. 

The trial compared three PrEP options including the lenacapavir injection to once-daily oral emtricitabine 200 mg and tenofovir-alafenamide 25 mg (F/TAF) and once-daily emtricitabine 200 mg and tenofovir–disoproxil fumarate 300 mg (F/TDF).

“Most participants in both the F/TAF and F/TDF groups had low adherence, and this declined over time,” Dr. Bekker reported. At 52 weeks, the vast majority of patients on both oral therapies had low adherence with dosing, defined at less than two doses a week.

Dr. Bekker called the adherence to the oral agents in this trial “disappointing.”

Findings from the trial underscore the challenges of adherence to a daily oral medication, Rochelle Walensky, MD, and Lindsey Baden, MD, from the Harvard Kennedy School of Government and Harvard Business School in Cambridge, Massachusetts, wrote in an editorial accompanying the published results.

With almost 92% attendance for the twice-yearly lenacapavir injections, the “well-done,” large, randomized, controlled trial “exemplifies not only that women can dependably adhere to this administration schedule, but also that levels of an HIV-1 capsid inhibitor can remain high enough over a period of 6 months to reliably prevent infection,” they added. 

Another key focus of the presentation was adverse events. The rate of adverse events grade 3 or more in the lenacapavir arm was 4.1%, Bekker said, which is slightly lower than the rates in the oral arms. The rates of serious adverse events were 2.8% for lenacapavir, 4% for F/TAF and 3.3% for F/TDF. 
 

Injection Site Reactions

Injection site reactions occurred in 68% of the lenacapavir group, including 63% with subcutaneous nodules.

The injection can form “a drug depot which may be palpable as a nodule,” Dr. Bekker said. In the placebo group, 34% of patients had injection-site reactions and 16% had nodules. Nearly all injection-site reactions were grade 1 or 2, she said. “Higher grade injection-site reactions were rare and not serious and occurred in a similar percentage in lenacapavir and placebo,” she said.

Overall, more than 25,000 injections of lenacapavir have been given, Dr. Bekker said, and four patients discontinued treatment because of injection-site reactions. “Reporting of injection-site reactions, including nodules, decreased with subsequent doses,” she said.

Contraception was not a requirement for enrollment in the study, Dr. Bekker pointed out, and pregnancy outcomes across the treatment arms were similar to the general population.
 

First in a Series of Trials

This is the first in a series of PURPOSE trials, Bekker reported. The phase 3 PURPOSE 2 trial, enrolling 3000 gay men, transgender women, transgender men and gender nonbinary people who have sex with male partners, is the second pivotal trial now underway.

Three other smaller trials are in the clinic in the United States and Europe.

PURPOSE 1 participants will continue to access lenacapavir until the product is available in South Africa and Uganda, Dr. Bekker said. Trial sponsor Gilead Sciences is also developing a direct licensing program to expedite generic access to the drug in high-incidence, resource-limited countries, she said.

Dr. Walensky and Dr. Baden report that lenacapavir currently costs about $43,000 annually in the United States. “But the results of the PURPOSE 1 trial have now created a moral imperative to make lenacapavir broadly accessible and affordable as PrEP” to people who were enrolled, as well as all those who are similarly eligible and could benefit.

So now we have a PrEP product with high efficacy, they added. “That is great news for science but not (yet) great for women.” 

Given the high pregnancy rate among participants in the PURPOSE 1 trial, Dr. Walensky and Dr. Baden point out the assessment of lenacapavir safety is a priority. They are also interested in learning more about drug resistance with this new option. 

“I f approved and delivered — rapidly, affordably, and equitably — to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention,” Dr. Lewin said.

Now, she added, “we eagerly await results from PURPOSE 2.”
 

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

Twice-yearly injections are 100% effective in preventing new infections, according to the final results from the PURPOSE 1 trial of lenacapavir.

For weeks, the HIV community has been talking about this highly anticipated clinical trial and whether the strong — and to many, surprising — interim results would hold at final presentation at the International AIDS Conference 2024 in Munich, Germany.

Presenting the results, Linda-Gail Bekker, MD, director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, reported zero new infections in those who got the shots in the study of about 5000 young women. In the group given daily oral preexposure prophylaxis (PrEP), roughly 2% contracted HIV from infected partners.

“A twice-yearly PrEP choice could overcome some of the adherence and persistence challenges and contribute critically to our quest to reduce HIV infection in women around the world,” Dr. Bekker said about the results, which were published simultaneously in The New England Journal of Medicine.

PURPOSE 1 confirmed that lenacapavir is a “breakthrough” for HIV prevention, said International AIDS Society president Sharon Lewin, PhD, MBBS. It has “huge public health potential,” said Dr. Lewin, the AIDS 2024 conference cochair and director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia.

Lenacapavir is a novel, first-in-class multistage HIV-1 capsid inhibitor with a long half-life, which enables the twice-yearly dosing.

PURPOSE 1 enrolled women aged 15-25 years who were at risk for HIV in South Africa and Uganda, with a primary endpoint of HIV infection. Because of the previously announced interim results, which showed the injection was preventing infections, study sponsor Gilead Sciences discontinued the randomized phase of the trial and shifted to an open-label design for lenacapavir.

“One hundred percent efficacy is more that we could ever have hoped for a potential prevention efficacy,” said Christoph Spinner, MD, MBA, an infectious disease specialist at the University Hospital of the Technical University of Munich and AIDS 2024 conference cochair.

Dr. Spinner added that while this is the first study of lenacapavir for PrEP, it’s also the first to explore outcomes of emtricitabine-tenofovir in cisgender women.
 

Strong Adherence Rates

The twice-yearly injection demonstrated adherence rates above 90% in the trial for both the 6- and 12-month injection intervals.

“Adherence was 91.5% at week 26 and 92.8% at week 52,” Dr. Bekker reported. 

The trial compared three PrEP options including the lenacapavir injection to once-daily oral emtricitabine 200 mg and tenofovir-alafenamide 25 mg (F/TAF) and once-daily emtricitabine 200 mg and tenofovir–disoproxil fumarate 300 mg (F/TDF).

“Most participants in both the F/TAF and F/TDF groups had low adherence, and this declined over time,” Dr. Bekker reported. At 52 weeks, the vast majority of patients on both oral therapies had low adherence with dosing, defined at less than two doses a week.

Dr. Bekker called the adherence to the oral agents in this trial “disappointing.”

Findings from the trial underscore the challenges of adherence to a daily oral medication, Rochelle Walensky, MD, and Lindsey Baden, MD, from the Harvard Kennedy School of Government and Harvard Business School in Cambridge, Massachusetts, wrote in an editorial accompanying the published results.

With almost 92% attendance for the twice-yearly lenacapavir injections, the “well-done,” large, randomized, controlled trial “exemplifies not only that women can dependably adhere to this administration schedule, but also that levels of an HIV-1 capsid inhibitor can remain high enough over a period of 6 months to reliably prevent infection,” they added. 

Another key focus of the presentation was adverse events. The rate of adverse events grade 3 or more in the lenacapavir arm was 4.1%, Bekker said, which is slightly lower than the rates in the oral arms. The rates of serious adverse events were 2.8% for lenacapavir, 4% for F/TAF and 3.3% for F/TDF. 
 

Injection Site Reactions

Injection site reactions occurred in 68% of the lenacapavir group, including 63% with subcutaneous nodules.

The injection can form “a drug depot which may be palpable as a nodule,” Dr. Bekker said. In the placebo group, 34% of patients had injection-site reactions and 16% had nodules. Nearly all injection-site reactions were grade 1 or 2, she said. “Higher grade injection-site reactions were rare and not serious and occurred in a similar percentage in lenacapavir and placebo,” she said.

Overall, more than 25,000 injections of lenacapavir have been given, Dr. Bekker said, and four patients discontinued treatment because of injection-site reactions. “Reporting of injection-site reactions, including nodules, decreased with subsequent doses,” she said.

Contraception was not a requirement for enrollment in the study, Dr. Bekker pointed out, and pregnancy outcomes across the treatment arms were similar to the general population.
 

First in a Series of Trials

This is the first in a series of PURPOSE trials, Bekker reported. The phase 3 PURPOSE 2 trial, enrolling 3000 gay men, transgender women, transgender men and gender nonbinary people who have sex with male partners, is the second pivotal trial now underway.

Three other smaller trials are in the clinic in the United States and Europe.

PURPOSE 1 participants will continue to access lenacapavir until the product is available in South Africa and Uganda, Dr. Bekker said. Trial sponsor Gilead Sciences is also developing a direct licensing program to expedite generic access to the drug in high-incidence, resource-limited countries, she said.

Dr. Walensky and Dr. Baden report that lenacapavir currently costs about $43,000 annually in the United States. “But the results of the PURPOSE 1 trial have now created a moral imperative to make lenacapavir broadly accessible and affordable as PrEP” to people who were enrolled, as well as all those who are similarly eligible and could benefit.

So now we have a PrEP product with high efficacy, they added. “That is great news for science but not (yet) great for women.” 

Given the high pregnancy rate among participants in the PURPOSE 1 trial, Dr. Walensky and Dr. Baden point out the assessment of lenacapavir safety is a priority. They are also interested in learning more about drug resistance with this new option. 

“I f approved and delivered — rapidly, affordably, and equitably — to those who need or want it, this long-acting tool could help accelerate global progress in HIV prevention,” Dr. Lewin said.

Now, she added, “we eagerly await results from PURPOSE 2.”
 

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

“We really aren’t taking care of records — we’re taking care of people.” — Dr. Lawrence Weed

What is the purpose of a progress note? Anyone? Yes, you there. “Insurance billing?” Yes, that’s a good one. Anyone else? “To remember what you did?” Excellent. Another? Yes, that’s right, for others to follow along in your care. These are all good reasons for a progress note to exist. But they aren’t the whole story. Let’s start at the beginning.

Charts were once a collection of paper sheets with handwritten notes. Sometimes illegible, sometimes beautiful, always efficient. A progress note back then could be just 10 characters, AK, LN2, X,X,X,X,X (with X’s marking nitrogen sprays). Then came the healthcare K-Pg event: the conversion to EMRs. Those doctors who survived evolved into computer programmers, creating blocks of text from a few keystrokes. But like toddler-sized Legos, the blocks made it impossible to build a note that is nuanced or precise. Worse yet, many notes consisting of blocks from one note added awkwardly to a new note, creating grotesque structures unrecognizable as anything that should exist in nature. Words and numbers, but no information.

Newtown grafitti / flickr / CC BY-2.0

Thanks to the eternity of EMR, these creations live on, hideous and useless. They waste not only the server’s energy but also our time. Few things are more maddening than scrolling to reach the bottom of another physician’s note only to find there is nothing there.

Whose fault is this? Anyone? Yes, that’s right, insurers. As there are probably no payers in this audience, let’s blame them. I agree, the crushing burden of documentation-to-get-reimbursed has forced us to create “notes” that add no value to us but add up points for us to get paid for them. CMS, payers, prior authorizations, and now even patients, it seems we are documenting for lots of people except for us. There isn’t time to satisfy all and this significant burden for every encounter is a proximate cause for doctors despair. Until now.

In 2024, came our story’s deus ex machina: the AI scribe. A tool that can listen to a doctor visit, then from the ether, generate a note. A fully formed, comprehensive, sometimes pretty note that satisfies all audiences. Dr. Larry Weed must be dancing in heaven. It was Dr. Weed who led us from the nicotine-stained logs of the 1950s to the powerful problem-based notes we use today, an innovation that rivals the stethoscope in its impact.

Professor Weed also predicted that computers would be important to capture and make sense of patient data, helping us make accurate diagnoses and efficient plans. Again, he was right. He would surely be advocating to take advantage of AI scribes’ marvelous ability to capture salient data and present it in the form of a problem-oriented medical record.

AI scribes will be ubiquitous soon; I’m fast and even for me they save time. They also allow, for the first time in a decade, to turn from the glow of a screen to actually face the patient – we no longer have to scribe and care simultaneously. Hallelujah. And yet, lest I disappoint you without a twist, it seems with AI scribes, like EMRs we lose a little something too.

Like self-driving cars or ChatGPT-generated letters, they remove cognitive loads. They are lovely when you have to multitask or are trying to recall a visit from hours (days) ago. Using them, you’ll feel faster, lighter, freer, happier. But what’s missing is the thinking. At the end, you have an exquisite note, but you didn’t write it. It has the salient points, but none of the mental work to create it. AI scribes subvert the valuable work of synthesis. That was the critical part of Dr. Weed’s discovery: writing problem-oriented notes helped us think better.

Kaiser Permanente

Writing allows for the friction that helps us process what is going on with a patient. It allows for the discovery of diagnoses and prompts plans. When I was an intern, one of my attendings would hand write notes, succinctly showing what he had observed and was thinking. He’d sketch diagrams in the chart, for example, to help illustrate how we’d work though the toxic, metabolic, and infectious etiologies of acute liver failure. Sublime.

The act of writing also helps remind us there is a person attached to these words. Like a handwritten sympathy card, it is intimate, human. Even using our EMR, I’d still often type sentences that help tell the patient’s story. “Her sister just died. Utterly devastated. I’ll forward chart to Bob (her PCP) to check in on her.” Or: “Scratch golfer wants to know why he is getting so many SCCs now. ‘Like bankruptcy, gradually then suddenly,’ I explained. I think I broke through.”

Since we’ve concluded the purpose of a note is mostly to capture data, AI scribes are a godsend. They do so with remarkable quality and efficiency. We’ll just have to remember if the diagnosis is unclear, then it might help to write the note out yourself. And even when done by the AI machine, we might add human touches now and again lest there be no art left in what we do.

“For sale. Sun hat. Never worn.”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

“We really aren’t taking care of records — we’re taking care of people.” — Dr. Lawrence Weed

What is the purpose of a progress note? Anyone? Yes, you there. “Insurance billing?” Yes, that’s a good one. Anyone else? “To remember what you did?” Excellent. Another? Yes, that’s right, for others to follow along in your care. These are all good reasons for a progress note to exist. But they aren’t the whole story. Let’s start at the beginning.

Charts were once a collection of paper sheets with handwritten notes. Sometimes illegible, sometimes beautiful, always efficient. A progress note back then could be just 10 characters, AK, LN2, X,X,X,X,X (with X’s marking nitrogen sprays). Then came the healthcare K-Pg event: the conversion to EMRs. Those doctors who survived evolved into computer programmers, creating blocks of text from a few keystrokes. But like toddler-sized Legos, the blocks made it impossible to build a note that is nuanced or precise. Worse yet, many notes consisting of blocks from one note added awkwardly to a new note, creating grotesque structures unrecognizable as anything that should exist in nature. Words and numbers, but no information.

Newtown grafitti / flickr / CC BY-2.0

Thanks to the eternity of EMR, these creations live on, hideous and useless. They waste not only the server’s energy but also our time. Few things are more maddening than scrolling to reach the bottom of another physician’s note only to find there is nothing there.

Whose fault is this? Anyone? Yes, that’s right, insurers. As there are probably no payers in this audience, let’s blame them. I agree, the crushing burden of documentation-to-get-reimbursed has forced us to create “notes” that add no value to us but add up points for us to get paid for them. CMS, payers, prior authorizations, and now even patients, it seems we are documenting for lots of people except for us. There isn’t time to satisfy all and this significant burden for every encounter is a proximate cause for doctors despair. Until now.

In 2024, came our story’s deus ex machina: the AI scribe. A tool that can listen to a doctor visit, then from the ether, generate a note. A fully formed, comprehensive, sometimes pretty note that satisfies all audiences. Dr. Larry Weed must be dancing in heaven. It was Dr. Weed who led us from the nicotine-stained logs of the 1950s to the powerful problem-based notes we use today, an innovation that rivals the stethoscope in its impact.

Professor Weed also predicted that computers would be important to capture and make sense of patient data, helping us make accurate diagnoses and efficient plans. Again, he was right. He would surely be advocating to take advantage of AI scribes’ marvelous ability to capture salient data and present it in the form of a problem-oriented medical record.

AI scribes will be ubiquitous soon; I’m fast and even for me they save time. They also allow, for the first time in a decade, to turn from the glow of a screen to actually face the patient – we no longer have to scribe and care simultaneously. Hallelujah. And yet, lest I disappoint you without a twist, it seems with AI scribes, like EMRs we lose a little something too.

Like self-driving cars or ChatGPT-generated letters, they remove cognitive loads. They are lovely when you have to multitask or are trying to recall a visit from hours (days) ago. Using them, you’ll feel faster, lighter, freer, happier. But what’s missing is the thinking. At the end, you have an exquisite note, but you didn’t write it. It has the salient points, but none of the mental work to create it. AI scribes subvert the valuable work of synthesis. That was the critical part of Dr. Weed’s discovery: writing problem-oriented notes helped us think better.

Kaiser Permanente

Writing allows for the friction that helps us process what is going on with a patient. It allows for the discovery of diagnoses and prompts plans. When I was an intern, one of my attendings would hand write notes, succinctly showing what he had observed and was thinking. He’d sketch diagrams in the chart, for example, to help illustrate how we’d work though the toxic, metabolic, and infectious etiologies of acute liver failure. Sublime.

The act of writing also helps remind us there is a person attached to these words. Like a handwritten sympathy card, it is intimate, human. Even using our EMR, I’d still often type sentences that help tell the patient’s story. “Her sister just died. Utterly devastated. I’ll forward chart to Bob (her PCP) to check in on her.” Or: “Scratch golfer wants to know why he is getting so many SCCs now. ‘Like bankruptcy, gradually then suddenly,’ I explained. I think I broke through.”

Since we’ve concluded the purpose of a note is mostly to capture data, AI scribes are a godsend. They do so with remarkable quality and efficiency. We’ll just have to remember if the diagnosis is unclear, then it might help to write the note out yourself. And even when done by the AI machine, we might add human touches now and again lest there be no art left in what we do.

“For sale. Sun hat. Never worn.”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

“We really aren’t taking care of records — we’re taking care of people.” — Dr. Lawrence Weed

What is the purpose of a progress note? Anyone? Yes, you there. “Insurance billing?” Yes, that’s a good one. Anyone else? “To remember what you did?” Excellent. Another? Yes, that’s right, for others to follow along in your care. These are all good reasons for a progress note to exist. But they aren’t the whole story. Let’s start at the beginning.

Charts were once a collection of paper sheets with handwritten notes. Sometimes illegible, sometimes beautiful, always efficient. A progress note back then could be just 10 characters, AK, LN2, X,X,X,X,X (with X’s marking nitrogen sprays). Then came the healthcare K-Pg event: the conversion to EMRs. Those doctors who survived evolved into computer programmers, creating blocks of text from a few keystrokes. But like toddler-sized Legos, the blocks made it impossible to build a note that is nuanced or precise. Worse yet, many notes consisting of blocks from one note added awkwardly to a new note, creating grotesque structures unrecognizable as anything that should exist in nature. Words and numbers, but no information.

Newtown grafitti / flickr / CC BY-2.0

Thanks to the eternity of EMR, these creations live on, hideous and useless. They waste not only the server’s energy but also our time. Few things are more maddening than scrolling to reach the bottom of another physician’s note only to find there is nothing there.

Whose fault is this? Anyone? Yes, that’s right, insurers. As there are probably no payers in this audience, let’s blame them. I agree, the crushing burden of documentation-to-get-reimbursed has forced us to create “notes” that add no value to us but add up points for us to get paid for them. CMS, payers, prior authorizations, and now even patients, it seems we are documenting for lots of people except for us. There isn’t time to satisfy all and this significant burden for every encounter is a proximate cause for doctors despair. Until now.

In 2024, came our story’s deus ex machina: the AI scribe. A tool that can listen to a doctor visit, then from the ether, generate a note. A fully formed, comprehensive, sometimes pretty note that satisfies all audiences. Dr. Larry Weed must be dancing in heaven. It was Dr. Weed who led us from the nicotine-stained logs of the 1950s to the powerful problem-based notes we use today, an innovation that rivals the stethoscope in its impact.

Professor Weed also predicted that computers would be important to capture and make sense of patient data, helping us make accurate diagnoses and efficient plans. Again, he was right. He would surely be advocating to take advantage of AI scribes’ marvelous ability to capture salient data and present it in the form of a problem-oriented medical record.

AI scribes will be ubiquitous soon; I’m fast and even for me they save time. They also allow, for the first time in a decade, to turn from the glow of a screen to actually face the patient – we no longer have to scribe and care simultaneously. Hallelujah. And yet, lest I disappoint you without a twist, it seems with AI scribes, like EMRs we lose a little something too.

Like self-driving cars or ChatGPT-generated letters, they remove cognitive loads. They are lovely when you have to multitask or are trying to recall a visit from hours (days) ago. Using them, you’ll feel faster, lighter, freer, happier. But what’s missing is the thinking. At the end, you have an exquisite note, but you didn’t write it. It has the salient points, but none of the mental work to create it. AI scribes subvert the valuable work of synthesis. That was the critical part of Dr. Weed’s discovery: writing problem-oriented notes helped us think better.

Kaiser Permanente

Writing allows for the friction that helps us process what is going on with a patient. It allows for the discovery of diagnoses and prompts plans. When I was an intern, one of my attendings would hand write notes, succinctly showing what he had observed and was thinking. He’d sketch diagrams in the chart, for example, to help illustrate how we’d work though the toxic, metabolic, and infectious etiologies of acute liver failure. Sublime.

The act of writing also helps remind us there is a person attached to these words. Like a handwritten sympathy card, it is intimate, human. Even using our EMR, I’d still often type sentences that help tell the patient’s story. “Her sister just died. Utterly devastated. I’ll forward chart to Bob (her PCP) to check in on her.” Or: “Scratch golfer wants to know why he is getting so many SCCs now. ‘Like bankruptcy, gradually then suddenly,’ I explained. I think I broke through.”

Since we’ve concluded the purpose of a note is mostly to capture data, AI scribes are a godsend. They do so with remarkable quality and efficiency. We’ll just have to remember if the diagnosis is unclear, then it might help to write the note out yourself. And even when done by the AI machine, we might add human touches now and again lest there be no art left in what we do.

“For sale. Sun hat. Never worn.”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

CHICAGO — Circulating tumor DNA (ctDNA) can predict relapse risk in some cases of early, high-risk breast cancer, but it’s too soon to use it to guide adjuvant therapy decisions, according to a study presented at the American Society of Clinical Oncology annual meeting.

Detectable ctDNA is “highly prognostic of worse outcomes, particularly in patients who [remain] persistently positive,” but the correlation isn’t perfect, said lead investigator Sherene Loi, MMBS, PhD, a breast cancer specialist at the Peter MacCallum Cancer Centre in Melbourne, Australia.

Although less likely, relapses also occurred in the study among women without ctDNA elevation. Conversely, there were women with elevated ctDNA who did not relapse, she said. The study was a subanalysis of the monarchE trial of adjuvant abemaciclib, a CDK 4/6 inhibitor.

Eventually, “we would like to use” ctDNA to guide adjuvant treatment decisions, but the research isn’t there yet, Dr. Loi said. It’s possible, for instance, that persistently detectable ctDNA indicates early treatment failure and the need for treatment intensification. Future research should tackle the issue.

Study discussant Francois-Clement Bidard, MD, PhD, a breast cancer specialist at Institut Curie, Paris, agreed that ctDNA isn’t ready for primetime in adjuvant early, high-risk breast cancer.

“There is no clinical evidence to suggest that there is clinical utility in this setting. There are several trials that are ongoing,” he said, but for now “you shouldn’t,” for example, “use ctDNA to de-escalate adjuvant CDK4/6 [inhibitors]. It could be in the future that we could have data on this, but at the moment, [the] clear clinical message [is] no way.”

At 5-year follow-up, the monarchE trial found a 7.6% invasive disease-free survival (IDFS) improvement when abemaciclib was added to the first 2 years of endocrine therapy in women with HR+, HER2-, node positive, high-risk early breast cancer. The combination is now a standard adjuvant option for the disease.

The ctDNA study focused on a subset of 910 subjects with adequate ctDNA testing to run the analysis. The study population was also selected to be enriched for overall IDFS events (27% versus 18% across the trial’s 5,637 subjects). An IDFS event was defined as a local, regional, contralateral or distant invasive recurrence; a new primary tumor; or death from any cause.

Testing was performed using the Signatera ctDNA assay. Baseline samples were taken after completion of adjuvant chemotherapy, then again at 3, 6, or 24 months.

Overall, ctDNA detection was infrequent. Just 8% of patients were positive at baseline and 17% were positive at any point during the trial. Even so, ctDNA detection at any point was adversely prognostic.

Patients who were ctDNA positive at baseline were more likely to experience an IDFS event, compared with those who were ctDNA negative at baseline (80% at 4 years follow-up versus 23%).

Similarly, those who remained positive or became positive during testing were more likely to experience an IDFS event compared with those who became negative or remained negative throughout testing.

For instance, all 34 patients who were positive at baseline and remained positive had an IDFS event by year 4, versus just 40% who started positive but then cleared their ctDNA.

Among women who were negative at baseline and remained negative, 13% had an IDFS event versus 89% who started negative but then turned positive. Subjects who turned positive also had the shortest time to an IDFS event, a median of 7 months.

Among women who recurred, those who were ctDNA negative tended to have local, regional, or contralateral recurrences, while ctDNA positive patients tended to have distant recurrences.

The finding “really highlights that ctDNA antedates the metastatic clinical relapse. What the ctDNA is telling you is that the metastatic process has been completed, and metastases are about to grow,” Dr. Bidard said.

The work was funded by Eli Lilly, maker of abemaciclib, with collaboration from Natera, maker of the Signatera assay. Dr. Loi is an adviser and researcher for Lilly, among other industry ties. Dr. Bidard is a speaker and consultant for Lilly, among other ties.

CHICAGO — Circulating tumor DNA (ctDNA) can predict relapse risk in some cases of early, high-risk breast cancer, but it’s too soon to use it to guide adjuvant therapy decisions, according to a study presented at the American Society of Clinical Oncology annual meeting.

Detectable ctDNA is “highly prognostic of worse outcomes, particularly in patients who [remain] persistently positive,” but the correlation isn’t perfect, said lead investigator Sherene Loi, MMBS, PhD, a breast cancer specialist at the Peter MacCallum Cancer Centre in Melbourne, Australia.

Although less likely, relapses also occurred in the study among women without ctDNA elevation. Conversely, there were women with elevated ctDNA who did not relapse, she said. The study was a subanalysis of the monarchE trial of adjuvant abemaciclib, a CDK 4/6 inhibitor.

Eventually, “we would like to use” ctDNA to guide adjuvant treatment decisions, but the research isn’t there yet, Dr. Loi said. It’s possible, for instance, that persistently detectable ctDNA indicates early treatment failure and the need for treatment intensification. Future research should tackle the issue.

Study discussant Francois-Clement Bidard, MD, PhD, a breast cancer specialist at Institut Curie, Paris, agreed that ctDNA isn’t ready for primetime in adjuvant early, high-risk breast cancer.

“There is no clinical evidence to suggest that there is clinical utility in this setting. There are several trials that are ongoing,” he said, but for now “you shouldn’t,” for example, “use ctDNA to de-escalate adjuvant CDK4/6 [inhibitors]. It could be in the future that we could have data on this, but at the moment, [the] clear clinical message [is] no way.”

At 5-year follow-up, the monarchE trial found a 7.6% invasive disease-free survival (IDFS) improvement when abemaciclib was added to the first 2 years of endocrine therapy in women with HR+, HER2-, node positive, high-risk early breast cancer. The combination is now a standard adjuvant option for the disease.

The ctDNA study focused on a subset of 910 subjects with adequate ctDNA testing to run the analysis. The study population was also selected to be enriched for overall IDFS events (27% versus 18% across the trial’s 5,637 subjects). An IDFS event was defined as a local, regional, contralateral or distant invasive recurrence; a new primary tumor; or death from any cause.

Testing was performed using the Signatera ctDNA assay. Baseline samples were taken after completion of adjuvant chemotherapy, then again at 3, 6, or 24 months.

Overall, ctDNA detection was infrequent. Just 8% of patients were positive at baseline and 17% were positive at any point during the trial. Even so, ctDNA detection at any point was adversely prognostic.

Patients who were ctDNA positive at baseline were more likely to experience an IDFS event, compared with those who were ctDNA negative at baseline (80% at 4 years follow-up versus 23%).

Similarly, those who remained positive or became positive during testing were more likely to experience an IDFS event compared with those who became negative or remained negative throughout testing.

For instance, all 34 patients who were positive at baseline and remained positive had an IDFS event by year 4, versus just 40% who started positive but then cleared their ctDNA.

Among women who were negative at baseline and remained negative, 13% had an IDFS event versus 89% who started negative but then turned positive. Subjects who turned positive also had the shortest time to an IDFS event, a median of 7 months.

Among women who recurred, those who were ctDNA negative tended to have local, regional, or contralateral recurrences, while ctDNA positive patients tended to have distant recurrences.

The finding “really highlights that ctDNA antedates the metastatic clinical relapse. What the ctDNA is telling you is that the metastatic process has been completed, and metastases are about to grow,” Dr. Bidard said.

The work was funded by Eli Lilly, maker of abemaciclib, with collaboration from Natera, maker of the Signatera assay. Dr. Loi is an adviser and researcher for Lilly, among other industry ties. Dr. Bidard is a speaker and consultant for Lilly, among other ties.

CHICAGO — Circulating tumor DNA (ctDNA) can predict relapse risk in some cases of early, high-risk breast cancer, but it’s too soon to use it to guide adjuvant therapy decisions, according to a study presented at the American Society of Clinical Oncology annual meeting.

Detectable ctDNA is “highly prognostic of worse outcomes, particularly in patients who [remain] persistently positive,” but the correlation isn’t perfect, said lead investigator Sherene Loi, MMBS, PhD, a breast cancer specialist at the Peter MacCallum Cancer Centre in Melbourne, Australia.

Although less likely, relapses also occurred in the study among women without ctDNA elevation. Conversely, there were women with elevated ctDNA who did not relapse, she said. The study was a subanalysis of the monarchE trial of adjuvant abemaciclib, a CDK 4/6 inhibitor.

Eventually, “we would like to use” ctDNA to guide adjuvant treatment decisions, but the research isn’t there yet, Dr. Loi said. It’s possible, for instance, that persistently detectable ctDNA indicates early treatment failure and the need for treatment intensification. Future research should tackle the issue.

Study discussant Francois-Clement Bidard, MD, PhD, a breast cancer specialist at Institut Curie, Paris, agreed that ctDNA isn’t ready for primetime in adjuvant early, high-risk breast cancer.

“There is no clinical evidence to suggest that there is clinical utility in this setting. There are several trials that are ongoing,” he said, but for now “you shouldn’t,” for example, “use ctDNA to de-escalate adjuvant CDK4/6 [inhibitors]. It could be in the future that we could have data on this, but at the moment, [the] clear clinical message [is] no way.”

At 5-year follow-up, the monarchE trial found a 7.6% invasive disease-free survival (IDFS) improvement when abemaciclib was added to the first 2 years of endocrine therapy in women with HR+, HER2-, node positive, high-risk early breast cancer. The combination is now a standard adjuvant option for the disease.

The ctDNA study focused on a subset of 910 subjects with adequate ctDNA testing to run the analysis. The study population was also selected to be enriched for overall IDFS events (27% versus 18% across the trial’s 5,637 subjects). An IDFS event was defined as a local, regional, contralateral or distant invasive recurrence; a new primary tumor; or death from any cause.

Testing was performed using the Signatera ctDNA assay. Baseline samples were taken after completion of adjuvant chemotherapy, then again at 3, 6, or 24 months.

Overall, ctDNA detection was infrequent. Just 8% of patients were positive at baseline and 17% were positive at any point during the trial. Even so, ctDNA detection at any point was adversely prognostic.

Patients who were ctDNA positive at baseline were more likely to experience an IDFS event, compared with those who were ctDNA negative at baseline (80% at 4 years follow-up versus 23%).

Similarly, those who remained positive or became positive during testing were more likely to experience an IDFS event compared with those who became negative or remained negative throughout testing.

For instance, all 34 patients who were positive at baseline and remained positive had an IDFS event by year 4, versus just 40% who started positive but then cleared their ctDNA.

Among women who were negative at baseline and remained negative, 13% had an IDFS event versus 89% who started negative but then turned positive. Subjects who turned positive also had the shortest time to an IDFS event, a median of 7 months.

Among women who recurred, those who were ctDNA negative tended to have local, regional, or contralateral recurrences, while ctDNA positive patients tended to have distant recurrences.

The finding “really highlights that ctDNA antedates the metastatic clinical relapse. What the ctDNA is telling you is that the metastatic process has been completed, and metastases are about to grow,” Dr. Bidard said.

The work was funded by Eli Lilly, maker of abemaciclib, with collaboration from Natera, maker of the Signatera assay. Dr. Loi is an adviser and researcher for Lilly, among other industry ties. Dr. Bidard is a speaker and consultant for Lilly, among other ties.

This transcript has been edited for clarity. 

Rachel S. Rubin, MD: I have an interesting topic for you — kind of shocking, actually. Some of you may have read a story earlier this year in The New York Times about the alarming rise among young people of choking or strangulation during sex. I spoke recently with Dr. Debby Herbenick about this concerning and violent trend. Dr. Herbenick is a well-known sexuality researcher and professor at the Indiana University School of Public Health. Welcome, Dr. Herbenick. Can you tell us about your research into this new trend?

Debby Herbenick, PhD: This is some of the most important research that I’ve done. I’ve been studying sexual behaviors and trends for about 14 years in terms of nationally representative studies that we do. Over time, we noticed a trend of increasing prevalence of rough sex practices. 

Now, there’s always been a lot of sexual diversity in the world throughout history. But the main trend that we have focused on in recent years that is important for everyone in medicine to know about is this rapid increase — actually, a really big increase — in what people call “sexual choking,” even though it’s a form of strangulation. The increase is mostly seen in teenagers and young adults. 

We’ve done US nationally representative surveys as well as college campus representative surveys. We find that consistently across four campus representative surveys that 64% of women report having ever been choked during sex, and around 1 in 3 women (aged 18-24 years) throughout the whole country report having been choked during their most recent sexual activity with another person. They call it choking, but because it involves usually one hand — sometimes two hands or a forearm or an object, like a belt or a cord to tie around the neck — it is technically strangulation, because it’s external pressure to the neck to reduce or stop airflow or blood flow. 

Dr. Rubin: These numbers are staggering, right? Everyone listening now is taking care of someone who has been strangled as a form of sexual pleasure. What does this mean from a safety perspective? And as doctors who are working these patients up for migraines and other health problems, what is the research showing? 

Dr. Herbenick: We certainly are seeing people report recurrent headaches and ringing in the ears. There are things we’ve just barely scratched the surface on. Those of us working in this space believe that for anybody coming in for an unexplained stroke (for example, under age 50), you might consider some imaging to see if they have a dissection. We are hearing about people who, when you really probe to find out whether they’ve had pressure on the neck, they report that indeed that they have. So, we have to be thinking about neurologic symptoms. We know that they’re experiencing these at a pretty high rate. 

For people who are engaging in these practices, they should know about the health risks, but we find that most don’t. They may have heard that if it’s really intense high pressure, that in rare cases people can die, but most have never heard of anything in between. So, they’re not necessarily connecting their voice hoarseness, or the recurrent headaches or the sensitivity to light they are having, to an experience of being choked. We need to be paying attention to neurologic symptoms. 

Most physicians I speak with at conferences say that where they feel like they can step into this conversation is through anticipatory guidance and letting their patients know that they may have heard about this trend, and a lot of people are talking about the health consequences, and I want to share some information with you — not coming at it from a place of shame or judgment, but providing some information so that [patients] actually get some medical facts about this that could be lifesaving. 

Dr. Rubin: I see such a big gap in my medical training. I was taught to say, “Hey, do you smoke, do you drink, do you do drugs? Do you have sex? Men, women, or both?”And that’s it. And then maybe use birth control, and don’t get an STD, thinking about herpes, syphilis, gonorrhea, and chlamydia. We weren’t really trained to talk to patients about what kind of sex they are having, or how to talk to patients in a way that is open-minded but also safety-conscious and how the concept of safe sex is more than wear a condom and use birth control.

This idea of rough sex practices and how to talk to teenagers — maybe our pediatricians should be talking about this. Where do we start in terms of how to bring up these conversations and with what level of detail? 

Dr. Herbenick: We find that some young people are already being asked about some of the effects that might be showing on their bodies. It might be that their provider notices some bruising, or marks on their bodies from other types of rough sex practices like hitting and spanking. So that could be an entry point there. Choking is far more prevalent than slapping, so if you’re seeing some marks on the body, then it’s also a good time to ask about other practices they might be engaging in, especially higher risk ones like choking or strangulation. It’s offering some information and even saying, “Look, I’m not here to shame or judge you. I just want you to have some information about this” and giving them an opportunity to ask questions, too. 

We have found that almost nobody talks with their nurse or doctor, even if they have symptoms after being choked or strangled during sex. Just 1% of women with choking-related symptoms, 7% of men, and far fewer trans and nonbinary young people report talking with a nurse or doctor, mostly because they say it doesn’t seem like a big deal. The symptoms got better quickly. Sometimes they’re afraid of being shamed for their sexual behavior, and that’s why they say they don’t talk with somebody. 

They need some type of open-door anticipatory guidance as a way forward. Not everyone is comfortable directly asking whether a patient is engaging in this, but at least letting people know that you’ve heard of this behavior and providing some medical facts can give us a step forward with creating these conversations. 

Dr. Rubin: Can you tell us where is this research going in terms of next steps? Other things that you’re looking at? And what are you excited about? 

Dr. Herbenick: I’m excited about some work I did with a collaborator and colleague of mine, Dr. Keisuke Kawata, that he led a couple of years ago. He’s a neuroscientist. We were looking at potential cumulative effects on the brain. Now we’re taking some of that research into its next steps. We’re also doing more focused studies on other health consequences and hopefully finding out how we can test different educational messages and get people to learn more fact-based information about this, and then see if that is effective in prevention. 

Dr. Rubin: It sounds like a public health campaign is really needed about how to get the word out there about the health consequences of these activities. We’re asking people often enough. In my clinic, I try to keep it open-ended — tell me what sex looks like. What does it look like, and what do you want it to look like? Because I see a lot of people with problems, but if they don’t bring it to me, I don’t necessarily bring it up to them. Until I heard your lecture, and I thought, oh my gosh, I’m not even asking the right questions. Are you hopeful that there will be more public health messaging out there? 

Dr. Herbenick: I am. Years ago, when the child and adolescent choking game became a thing, the Centers for Disease Control and Prevention (CDC) issued reports about it and warnings to parents. And this is a far, far higher prevalence than that ever was. So, I would love to see organizations like the CDC and medical groups getting involved and educating their members and making statements. This is really impacting a huge generation of girls and women, because when it happens during sex between women and men, the choking is mostly happening to the girls and women. It’s also prevalent among sexual minority individuals. But we are talking about this whole generation of young women and what’s happening to their bodies and their brain health. We really need to step into this conversation. 

Dr. Rubin: Very few of us are sexual medicine–trained physicians, and very few of us feel confident and comfortable talking about sexual health issues. But people are getting hurt. People are having real consequences of these behaviors because of our lack of education, knowledge, and even discussion around it. So thank you for doing this research, because had you not done this research, we wouldn’t have found out that 64% of people are engaging in these types of activities. That is not rare.

Dr. Rubin is an assistant clinical professor, Department of Urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity. 

Rachel S. Rubin, MD: I have an interesting topic for you — kind of shocking, actually. Some of you may have read a story earlier this year in The New York Times about the alarming rise among young people of choking or strangulation during sex. I spoke recently with Dr. Debby Herbenick about this concerning and violent trend. Dr. Herbenick is a well-known sexuality researcher and professor at the Indiana University School of Public Health. Welcome, Dr. Herbenick. Can you tell us about your research into this new trend?

Debby Herbenick, PhD: This is some of the most important research that I’ve done. I’ve been studying sexual behaviors and trends for about 14 years in terms of nationally representative studies that we do. Over time, we noticed a trend of increasing prevalence of rough sex practices. 

Now, there’s always been a lot of sexual diversity in the world throughout history. But the main trend that we have focused on in recent years that is important for everyone in medicine to know about is this rapid increase — actually, a really big increase — in what people call “sexual choking,” even though it’s a form of strangulation. The increase is mostly seen in teenagers and young adults. 

We’ve done US nationally representative surveys as well as college campus representative surveys. We find that consistently across four campus representative surveys that 64% of women report having ever been choked during sex, and around 1 in 3 women (aged 18-24 years) throughout the whole country report having been choked during their most recent sexual activity with another person. They call it choking, but because it involves usually one hand — sometimes two hands or a forearm or an object, like a belt or a cord to tie around the neck — it is technically strangulation, because it’s external pressure to the neck to reduce or stop airflow or blood flow. 

Dr. Rubin: These numbers are staggering, right? Everyone listening now is taking care of someone who has been strangled as a form of sexual pleasure. What does this mean from a safety perspective? And as doctors who are working these patients up for migraines and other health problems, what is the research showing? 

Dr. Herbenick: We certainly are seeing people report recurrent headaches and ringing in the ears. There are things we’ve just barely scratched the surface on. Those of us working in this space believe that for anybody coming in for an unexplained stroke (for example, under age 50), you might consider some imaging to see if they have a dissection. We are hearing about people who, when you really probe to find out whether they’ve had pressure on the neck, they report that indeed that they have. So, we have to be thinking about neurologic symptoms. We know that they’re experiencing these at a pretty high rate. 

For people who are engaging in these practices, they should know about the health risks, but we find that most don’t. They may have heard that if it’s really intense high pressure, that in rare cases people can die, but most have never heard of anything in between. So, they’re not necessarily connecting their voice hoarseness, or the recurrent headaches or the sensitivity to light they are having, to an experience of being choked. We need to be paying attention to neurologic symptoms. 

Most physicians I speak with at conferences say that where they feel like they can step into this conversation is through anticipatory guidance and letting their patients know that they may have heard about this trend, and a lot of people are talking about the health consequences, and I want to share some information with you — not coming at it from a place of shame or judgment, but providing some information so that [patients] actually get some medical facts about this that could be lifesaving. 

Dr. Rubin: I see such a big gap in my medical training. I was taught to say, “Hey, do you smoke, do you drink, do you do drugs? Do you have sex? Men, women, or both?”And that’s it. And then maybe use birth control, and don’t get an STD, thinking about herpes, syphilis, gonorrhea, and chlamydia. We weren’t really trained to talk to patients about what kind of sex they are having, or how to talk to patients in a way that is open-minded but also safety-conscious and how the concept of safe sex is more than wear a condom and use birth control.

This idea of rough sex practices and how to talk to teenagers — maybe our pediatricians should be talking about this. Where do we start in terms of how to bring up these conversations and with what level of detail? 

Dr. Herbenick: We find that some young people are already being asked about some of the effects that might be showing on their bodies. It might be that their provider notices some bruising, or marks on their bodies from other types of rough sex practices like hitting and spanking. So that could be an entry point there. Choking is far more prevalent than slapping, so if you’re seeing some marks on the body, then it’s also a good time to ask about other practices they might be engaging in, especially higher risk ones like choking or strangulation. It’s offering some information and even saying, “Look, I’m not here to shame or judge you. I just want you to have some information about this” and giving them an opportunity to ask questions, too. 

We have found that almost nobody talks with their nurse or doctor, even if they have symptoms after being choked or strangled during sex. Just 1% of women with choking-related symptoms, 7% of men, and far fewer trans and nonbinary young people report talking with a nurse or doctor, mostly because they say it doesn’t seem like a big deal. The symptoms got better quickly. Sometimes they’re afraid of being shamed for their sexual behavior, and that’s why they say they don’t talk with somebody. 

They need some type of open-door anticipatory guidance as a way forward. Not everyone is comfortable directly asking whether a patient is engaging in this, but at least letting people know that you’ve heard of this behavior and providing some medical facts can give us a step forward with creating these conversations. 

Dr. Rubin: Can you tell us where is this research going in terms of next steps? Other things that you’re looking at? And what are you excited about? 

Dr. Herbenick: I’m excited about some work I did with a collaborator and colleague of mine, Dr. Keisuke Kawata, that he led a couple of years ago. He’s a neuroscientist. We were looking at potential cumulative effects on the brain. Now we’re taking some of that research into its next steps. We’re also doing more focused studies on other health consequences and hopefully finding out how we can test different educational messages and get people to learn more fact-based information about this, and then see if that is effective in prevention. 

Dr. Rubin: It sounds like a public health campaign is really needed about how to get the word out there about the health consequences of these activities. We’re asking people often enough. In my clinic, I try to keep it open-ended — tell me what sex looks like. What does it look like, and what do you want it to look like? Because I see a lot of people with problems, but if they don’t bring it to me, I don’t necessarily bring it up to them. Until I heard your lecture, and I thought, oh my gosh, I’m not even asking the right questions. Are you hopeful that there will be more public health messaging out there? 

Dr. Herbenick: I am. Years ago, when the child and adolescent choking game became a thing, the Centers for Disease Control and Prevention (CDC) issued reports about it and warnings to parents. And this is a far, far higher prevalence than that ever was. So, I would love to see organizations like the CDC and medical groups getting involved and educating their members and making statements. This is really impacting a huge generation of girls and women, because when it happens during sex between women and men, the choking is mostly happening to the girls and women. It’s also prevalent among sexual minority individuals. But we are talking about this whole generation of young women and what’s happening to their bodies and their brain health. We really need to step into this conversation. 

Dr. Rubin: Very few of us are sexual medicine–trained physicians, and very few of us feel confident and comfortable talking about sexual health issues. But people are getting hurt. People are having real consequences of these behaviors because of our lack of education, knowledge, and even discussion around it. So thank you for doing this research, because had you not done this research, we wouldn’t have found out that 64% of people are engaging in these types of activities. That is not rare.

Dr. Rubin is an assistant clinical professor, Department of Urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity. 

Rachel S. Rubin, MD: I have an interesting topic for you — kind of shocking, actually. Some of you may have read a story earlier this year in The New York Times about the alarming rise among young people of choking or strangulation during sex. I spoke recently with Dr. Debby Herbenick about this concerning and violent trend. Dr. Herbenick is a well-known sexuality researcher and professor at the Indiana University School of Public Health. Welcome, Dr. Herbenick. Can you tell us about your research into this new trend?

Debby Herbenick, PhD: This is some of the most important research that I’ve done. I’ve been studying sexual behaviors and trends for about 14 years in terms of nationally representative studies that we do. Over time, we noticed a trend of increasing prevalence of rough sex practices. 

Now, there’s always been a lot of sexual diversity in the world throughout history. But the main trend that we have focused on in recent years that is important for everyone in medicine to know about is this rapid increase — actually, a really big increase — in what people call “sexual choking,” even though it’s a form of strangulation. The increase is mostly seen in teenagers and young adults. 

We’ve done US nationally representative surveys as well as college campus representative surveys. We find that consistently across four campus representative surveys that 64% of women report having ever been choked during sex, and around 1 in 3 women (aged 18-24 years) throughout the whole country report having been choked during their most recent sexual activity with another person. They call it choking, but because it involves usually one hand — sometimes two hands or a forearm or an object, like a belt or a cord to tie around the neck — it is technically strangulation, because it’s external pressure to the neck to reduce or stop airflow or blood flow. 

Dr. Rubin: These numbers are staggering, right? Everyone listening now is taking care of someone who has been strangled as a form of sexual pleasure. What does this mean from a safety perspective? And as doctors who are working these patients up for migraines and other health problems, what is the research showing? 

Dr. Herbenick: We certainly are seeing people report recurrent headaches and ringing in the ears. There are things we’ve just barely scratched the surface on. Those of us working in this space believe that for anybody coming in for an unexplained stroke (for example, under age 50), you might consider some imaging to see if they have a dissection. We are hearing about people who, when you really probe to find out whether they’ve had pressure on the neck, they report that indeed that they have. So, we have to be thinking about neurologic symptoms. We know that they’re experiencing these at a pretty high rate. 

For people who are engaging in these practices, they should know about the health risks, but we find that most don’t. They may have heard that if it’s really intense high pressure, that in rare cases people can die, but most have never heard of anything in between. So, they’re not necessarily connecting their voice hoarseness, or the recurrent headaches or the sensitivity to light they are having, to an experience of being choked. We need to be paying attention to neurologic symptoms. 

Most physicians I speak with at conferences say that where they feel like they can step into this conversation is through anticipatory guidance and letting their patients know that they may have heard about this trend, and a lot of people are talking about the health consequences, and I want to share some information with you — not coming at it from a place of shame or judgment, but providing some information so that [patients] actually get some medical facts about this that could be lifesaving. 

Dr. Rubin: I see such a big gap in my medical training. I was taught to say, “Hey, do you smoke, do you drink, do you do drugs? Do you have sex? Men, women, or both?”And that’s it. And then maybe use birth control, and don’t get an STD, thinking about herpes, syphilis, gonorrhea, and chlamydia. We weren’t really trained to talk to patients about what kind of sex they are having, or how to talk to patients in a way that is open-minded but also safety-conscious and how the concept of safe sex is more than wear a condom and use birth control.

This idea of rough sex practices and how to talk to teenagers — maybe our pediatricians should be talking about this. Where do we start in terms of how to bring up these conversations and with what level of detail? 

Dr. Herbenick: We find that some young people are already being asked about some of the effects that might be showing on their bodies. It might be that their provider notices some bruising, or marks on their bodies from other types of rough sex practices like hitting and spanking. So that could be an entry point there. Choking is far more prevalent than slapping, so if you’re seeing some marks on the body, then it’s also a good time to ask about other practices they might be engaging in, especially higher risk ones like choking or strangulation. It’s offering some information and even saying, “Look, I’m not here to shame or judge you. I just want you to have some information about this” and giving them an opportunity to ask questions, too. 

We have found that almost nobody talks with their nurse or doctor, even if they have symptoms after being choked or strangled during sex. Just 1% of women with choking-related symptoms, 7% of men, and far fewer trans and nonbinary young people report talking with a nurse or doctor, mostly because they say it doesn’t seem like a big deal. The symptoms got better quickly. Sometimes they’re afraid of being shamed for their sexual behavior, and that’s why they say they don’t talk with somebody. 

They need some type of open-door anticipatory guidance as a way forward. Not everyone is comfortable directly asking whether a patient is engaging in this, but at least letting people know that you’ve heard of this behavior and providing some medical facts can give us a step forward with creating these conversations. 

Dr. Rubin: Can you tell us where is this research going in terms of next steps? Other things that you’re looking at? And what are you excited about? 

Dr. Herbenick: I’m excited about some work I did with a collaborator and colleague of mine, Dr. Keisuke Kawata, that he led a couple of years ago. He’s a neuroscientist. We were looking at potential cumulative effects on the brain. Now we’re taking some of that research into its next steps. We’re also doing more focused studies on other health consequences and hopefully finding out how we can test different educational messages and get people to learn more fact-based information about this, and then see if that is effective in prevention. 

Dr. Rubin: It sounds like a public health campaign is really needed about how to get the word out there about the health consequences of these activities. We’re asking people often enough. In my clinic, I try to keep it open-ended — tell me what sex looks like. What does it look like, and what do you want it to look like? Because I see a lot of people with problems, but if they don’t bring it to me, I don’t necessarily bring it up to them. Until I heard your lecture, and I thought, oh my gosh, I’m not even asking the right questions. Are you hopeful that there will be more public health messaging out there? 

Dr. Herbenick: I am. Years ago, when the child and adolescent choking game became a thing, the Centers for Disease Control and Prevention (CDC) issued reports about it and warnings to parents. And this is a far, far higher prevalence than that ever was. So, I would love to see organizations like the CDC and medical groups getting involved and educating their members and making statements. This is really impacting a huge generation of girls and women, because when it happens during sex between women and men, the choking is mostly happening to the girls and women. It’s also prevalent among sexual minority individuals. But we are talking about this whole generation of young women and what’s happening to their bodies and their brain health. We really need to step into this conversation. 

Dr. Rubin: Very few of us are sexual medicine–trained physicians, and very few of us feel confident and comfortable talking about sexual health issues. But people are getting hurt. People are having real consequences of these behaviors because of our lack of education, knowledge, and even discussion around it. So thank you for doing this research, because had you not done this research, we wouldn’t have found out that 64% of people are engaging in these types of activities. That is not rare.

Dr. Rubin is an assistant clinical professor, Department of Urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

TOPLINE:

The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.

METHODOLOGY:

• Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
• Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
• The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
• The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
• A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).

TAKEAWAY:

• Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
• The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
• Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
• False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).

IN PRACTICE:

This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.

SOURCE:

The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.

The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option. 
 

DISCLOSURES:

Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.

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

TOPLINE:

The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.

METHODOLOGY:

• Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
• Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
• The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
• The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
• A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).

TAKEAWAY:

• Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
• The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
• Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
• False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).

IN PRACTICE:

This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.

SOURCE:

The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.

The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option. 
 

DISCLOSURES:

Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.

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

TOPLINE:

The transvaginal ultrasonography triage strategy is unreliable for diagnosing endometrial cancer in high-risk Black women, with a significant risk for false-negative results at different endometrial thickness thresholds.

METHODOLOGY:

• Poor performance of transvaginal ultrasonography-measured endometrial thickness as a diagnostic triage strategy for endometrial cancer may contribute to racial disparity in stage at diagnosis between Black and White women.
• Researchers assessed the false-negative probability using transvaginal ultrasonography-measured endometrial thickness thresholds as triage for endometrial cancer in 1494 Black women (median age, 46 years) who underwent hysterectomy.
• The researchers focused on endometrial thickness measurements recorded within 24 months before hysterectomy, as well as demographic and clinical data.
• The endometrial thickness thresholds were defined as < 3 mm, < 4 mm, and < 5 mm, with the rest grouped as ≥ 5 mm, consistent with guidelines.
• A total of 210 women had endometrial cancer. The most common presenting symptoms were fibroids (78%), vaginal bleeding (71%), and pelvic pain (57%).

TAKEAWAY:

• Twenty-four cases of endometrial cancer were below the 5-mm endometrial thickness threshold that would trigger biopsy, resulting overall in 11.4% of endometrial cancer cases potentially missed.
• The false-negative probability was 9.5% (20 cases) at the < 4-mm threshold and 3.8% (8 cases) at the < 3-mm threshold.
• Classic risk factors for endometrial cancer (postmenopausal bleeding, age ≥ 50 years, and BMI > 40) did not result in improved performance of the endometrial thickness triage strategy.
• False-negative probability was also similar among those with fibroids (12%) but higher in the setting of partial endometrial thickness visibility (26%) and pelvic pain (15%).

IN PRACTICE:

This study reveals a “concerning error rate for a triage strategy that would terminate further workup and provide false reassurance to both patients and physicians.” The results contribute to “an increasing body of work questioning the wisdom of the (transvaginal ultrasonography) triage strategy. It may be the case that the (transvaginal ultrasonography) triage for endometrial biopsy is no longer a preferred strategy in the setting of increasing endometrial cancer rates for all. For Black patients with concerning symptoms, tissue biopsy is recommended to avoid misdiagnosis of endometrial cancer,” the researchers concluded.

SOURCE:

The study, with first author Kemi M. Doll, MD, Fred Hutchinson Cancer Center, University of Washington, Seattle, was published online in JAMA Oncology.

LIMITATIONS:

The study did not include cases where transvaginal ultrasonography reports omitted endometrial thickness measurements or reported nonvisible endometrial thickness, possibly underestimating the failure rate of the transvaginal ultrasonography triage strategy.

The sample did not include endometrial cancer cases that were not treated with hysterectomy, which may occur in young women with grade 1 endometrial cancer, those medically incapable of undergoing surgery, and those with disease so advanced that surgery is no longer an option. 
 

DISCLOSURES:

Funding was provided by Kuni Discovery Grants for Cancer Research: Advancing Innovation and by a grant from the National Institutes of Health. Dr. Doll reported receiving investigator-initiated research grants from the Patient Centered Outcomes Research Institute, American Association of Cancer Research, and Merck.

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

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.