Commentary

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Danielle Kiefer ([email protected]), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Danielle Kiefer ([email protected]), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Danielle Kiefer ([email protected]), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

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

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

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

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

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

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with skin barrier impairment and immune system dysregulation.¹ Development of AD in young children can present challenges in determining appropriate treatment regimens. Natural remedies for AD often are promoted on social media over traditional treatments, including topical corticosteroids (TCSs), which can contribute to corticophobia.² Dermatologists play a critical role not only in optimizing topical therapy but also addressing patient interest in natural approaches to AD, including diet-related questions. This article outlines the role of diet and probiotics in pediatric AD and reviews the topical treatments currently approved for this patient population.

Diet and Probiotics

With a growing focus on natural therapies for AD, dietary interventions have come to the forefront. A prevalent theme among patients and their families is addressing gut health and allergic triggers. Broad elimination diets have not shown clinical benefit in patients with AD regardless of age,³ and in children, they may result in nutritional deficiencies, poor growth, and increased risk for IgE-mediated food allergies.⁴ If a true food allergy is identified based on positive IgE and an acute clinical reaction, elimination of the allergen may provide some benefit.⁵

The link between gut microbiota and skin health has driven an interest in the role of probiotics in the treatment of pediatric AD. A meta-analysis of 20 articles concluded that, whether administered to infants or breastfeeding mothers, use of probiotics overall led to a significant reduction in AD risk in infants (P=.001). Lactobacillus and mixed strains were effective.⁶ While broad elimination diets are not used to treat AD, probiotic supplementation can be considered for prevention of AD.

Topical Corticosteroids

Topical corticosteroids are the cornerstone of AD treatment; however, corticophobia among patients is on the rise, leading to poor adherence and suboptimal control of AD.⁷ Mild cutaneous adverse effects (AEs) including skin atrophy, striae, and telangiectasias may occur. Rarely, systemic AEs occur due to absorption of TCSs into the bloodstream, mainly with application of potent steroids over large body surface areas or under occlusion.⁸ When the optimal potency of a TCS is chosen and used appropriately, incidence of AEs from TCS use is very low.⁹

Counseling parents about risk factors that can lead to AEs during treatment with TCSs and formulating regimens that minimize these risks while maintaining efficacy increases adherence and outcomes. Pulse maintenance dosing of TCSs typically involves application 1 to 2 times weekly to areas of the skin that are prone to frequent outbreaks. Pulse maintenance dosing can reduce the incidence of AD flares while also decreasing the total amount of topical medication needed as compared to the reactive approach alone, thereby reducing risk for AEs.⁸

Steroid-Sparing Topical Treatments

Although TCSs are considered first-line agents, recently there has been an advent of steroid-sparing topical agents approved by the US Food and Drug Administration (FDA) for pediatric patients with AD, including topical calcineurin inhibitors (TCIs), phosphodiesterase 4 inhibitors, a Janus kinase inhibitor, and aryl hydrocarbon receptor agonists. Offering steroid-sparing agents in these patients can help ease parental anxiety regarding TCS overuse.

Topical Calcineurin Inhibitors—Pimecrolimus cream 1% and tacrolimus ointment 0.03% are approved for patients aged 2 years and older and have anti-inflammatory and antipruritic effects equivalent to low-potency TCS. Tacrolimus ­ointment 0.1% is approved for patients aged 16 years and older with similar efficacy to a midpotency TCSs. Pimecrolimus cream 1% and tacrolimus ointment 0.03% often are used off-label in ­children younger than 2 years, as supported by clinical trials showing their safety and efficacy.¹⁰ 

Topical calcineurin inhibitors can replace or supplement TCSs, making TCIs a desirable option for avoidance of steroid-related AEs. The addition of a TCI to spot treatment or a pulse regimen in a young patient can reassure them and their caregivers that the provider is proactively reducing the risk of TCS overuse. The largest barrier to TCI use is the FDA’s black box warning based on the oral formulation of tacrolimus, citing a potential increased risk for lymphoma and skin cancer; however, there is no evidence for substantial systemic absorption of topical pimecrolimus or tacrolimus.¹¹ Large task-force reviews have found no association between TCI use and development of malignancy.^12,13 Based on the current data, counseling patients and their caregivers that this risk primarily is theoretical may help them more confidently integrate TCIs into their treatment regimen. Burning and tingling may occur in a minority of pediatric patients using TCIs for AD. Applying the medication to open wounds or inflamed skin increases the risk for stinging, but pretreatment with a short course of TCSs before transitioning to a TCI may boost tolerance.¹⁴ 

Phosphodiesterase 4 Inhibitors—Crisaborole ointment 2%, a phosphodiesterase 4 inhibitor, is approved for children aged 3 months and older with mild to moderate AD. Its use has been more limited than TCSs and TCIs, as local irritation including stinging and burning can occur in up to 50% of patients.¹⁵ One study comparing crisaborole 2% with tacrolimus 0.03% revealed greater improvement with tacrolimus.¹⁶ A second phosphodiesterase 4 inhibitor approved for once-daily use in children aged 6 years and older with mild to moderate AD is roflumilast cream 0.15%. Roflumilast reduces eczema severity and pruritus, with AEs also limited to application-site stinging and burning.¹⁷ 

Janus Kinase Inhibitor—Ruxolitinib cream 1.5%, a Janus kinase inhibitor, has been approved by the FDA since 2023 for twice-daily use in children aged 12 years and older with AD. Similar to TCIs, ruxolitinib cream carries a black box warning. Short-term safety data on ruxolitinib cream have revealed low levels of ruxolitinib concentration in plasma¹⁸; however, long-term studies on topical Janus kinase inhibitors for AD in pediatric and adult populations are lacking. To reduce the risk for systemic absorption, recommendations include limiting usage to 60 g per week and limiting treatment to less than 20% of the body surface area.¹⁹ Ruxolitinib has efficacy similar to or possibly superior to triamcinolone 0.1%.²⁰ Ruxolitinib is emerging as a promising nonsteroidal option that potentially is highly efficacious and well tolerated without cutaneous AEs.  

Aryl Hydrocarbon Receptor Agonist—Tapinarof cream 1% is an aryl hydrocarbon receptor agonist that has been approved by the FDA since 2024 for children aged 2 years and older as a once-daily treatment for moderate to severe AD. Adverse events include folliculitis, nasopharyngitis, and headache, which are mostly mild or moderate.²¹

Final Thoughts

Topical management of pediatric AD includes traditional therapy with TCSs and newer steroid-sparing agents, which can help address corticophobia. Anticipatory guidance regarding the safety and long-term effects of individual therapies is critical to ensuring patient adherence to treatment regimens. Probiotics may help prevent pediatric AD, but future studies are needed to determine their role in treatment.

Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with skin barrier impairment and immune system dysregulation.¹ Development of AD in young children can present challenges in determining appropriate treatment regimens. Natural remedies for AD often are promoted on social media over traditional treatments, including topical corticosteroids (TCSs), which can contribute to corticophobia.² Dermatologists play a critical role not only in optimizing topical therapy but also addressing patient interest in natural approaches to AD, including diet-related questions. This article outlines the role of diet and probiotics in pediatric AD and reviews the topical treatments currently approved for this patient population.

Diet and Probiotics

With a growing focus on natural therapies for AD, dietary interventions have come to the forefront. A prevalent theme among patients and their families is addressing gut health and allergic triggers. Broad elimination diets have not shown clinical benefit in patients with AD regardless of age,³ and in children, they may result in nutritional deficiencies, poor growth, and increased risk for IgE-mediated food allergies.⁴ If a true food allergy is identified based on positive IgE and an acute clinical reaction, elimination of the allergen may provide some benefit.⁵

The link between gut microbiota and skin health has driven an interest in the role of probiotics in the treatment of pediatric AD. A meta-analysis of 20 articles concluded that, whether administered to infants or breastfeeding mothers, use of probiotics overall led to a significant reduction in AD risk in infants (P=.001). Lactobacillus and mixed strains were effective.⁶ While broad elimination diets are not used to treat AD, probiotic supplementation can be considered for prevention of AD.

Topical Corticosteroids

Topical corticosteroids are the cornerstone of AD treatment; however, corticophobia among patients is on the rise, leading to poor adherence and suboptimal control of AD.⁷ Mild cutaneous adverse effects (AEs) including skin atrophy, striae, and telangiectasias may occur. Rarely, systemic AEs occur due to absorption of TCSs into the bloodstream, mainly with application of potent steroids over large body surface areas or under occlusion.⁸ When the optimal potency of a TCS is chosen and used appropriately, incidence of AEs from TCS use is very low.⁹

Counseling parents about risk factors that can lead to AEs during treatment with TCSs and formulating regimens that minimize these risks while maintaining efficacy increases adherence and outcomes. Pulse maintenance dosing of TCSs typically involves application 1 to 2 times weekly to areas of the skin that are prone to frequent outbreaks. Pulse maintenance dosing can reduce the incidence of AD flares while also decreasing the total amount of topical medication needed as compared to the reactive approach alone, thereby reducing risk for AEs.⁸

Steroid-Sparing Topical Treatments

Although TCSs are considered first-line agents, recently there has been an advent of steroid-sparing topical agents approved by the US Food and Drug Administration (FDA) for pediatric patients with AD, including topical calcineurin inhibitors (TCIs), phosphodiesterase 4 inhibitors, a Janus kinase inhibitor, and aryl hydrocarbon receptor agonists. Offering steroid-sparing agents in these patients can help ease parental anxiety regarding TCS overuse.

Topical Calcineurin Inhibitors—Pimecrolimus cream 1% and tacrolimus ointment 0.03% are approved for patients aged 2 years and older and have anti-inflammatory and antipruritic effects equivalent to low-potency TCS. Tacrolimus ­ointment 0.1% is approved for patients aged 16 years and older with similar efficacy to a midpotency TCSs. Pimecrolimus cream 1% and tacrolimus ointment 0.03% often are used off-label in ­children younger than 2 years, as supported by clinical trials showing their safety and efficacy.¹⁰ 

Topical calcineurin inhibitors can replace or supplement TCSs, making TCIs a desirable option for avoidance of steroid-related AEs. The addition of a TCI to spot treatment or a pulse regimen in a young patient can reassure them and their caregivers that the provider is proactively reducing the risk of TCS overuse. The largest barrier to TCI use is the FDA’s black box warning based on the oral formulation of tacrolimus, citing a potential increased risk for lymphoma and skin cancer; however, there is no evidence for substantial systemic absorption of topical pimecrolimus or tacrolimus.¹¹ Large task-force reviews have found no association between TCI use and development of malignancy.^12,13 Based on the current data, counseling patients and their caregivers that this risk primarily is theoretical may help them more confidently integrate TCIs into their treatment regimen. Burning and tingling may occur in a minority of pediatric patients using TCIs for AD. Applying the medication to open wounds or inflamed skin increases the risk for stinging, but pretreatment with a short course of TCSs before transitioning to a TCI may boost tolerance.¹⁴ 

Phosphodiesterase 4 Inhibitors—Crisaborole ointment 2%, a phosphodiesterase 4 inhibitor, is approved for children aged 3 months and older with mild to moderate AD. Its use has been more limited than TCSs and TCIs, as local irritation including stinging and burning can occur in up to 50% of patients.¹⁵ One study comparing crisaborole 2% with tacrolimus 0.03% revealed greater improvement with tacrolimus.¹⁶ A second phosphodiesterase 4 inhibitor approved for once-daily use in children aged 6 years and older with mild to moderate AD is roflumilast cream 0.15%. Roflumilast reduces eczema severity and pruritus, with AEs also limited to application-site stinging and burning.¹⁷ 

Janus Kinase Inhibitor—Ruxolitinib cream 1.5%, a Janus kinase inhibitor, has been approved by the FDA since 2023 for twice-daily use in children aged 12 years and older with AD. Similar to TCIs, ruxolitinib cream carries a black box warning. Short-term safety data on ruxolitinib cream have revealed low levels of ruxolitinib concentration in plasma¹⁸; however, long-term studies on topical Janus kinase inhibitors for AD in pediatric and adult populations are lacking. To reduce the risk for systemic absorption, recommendations include limiting usage to 60 g per week and limiting treatment to less than 20% of the body surface area.¹⁹ Ruxolitinib has efficacy similar to or possibly superior to triamcinolone 0.1%.²⁰ Ruxolitinib is emerging as a promising nonsteroidal option that potentially is highly efficacious and well tolerated without cutaneous AEs.  

Aryl Hydrocarbon Receptor Agonist—Tapinarof cream 1% is an aryl hydrocarbon receptor agonist that has been approved by the FDA since 2024 for children aged 2 years and older as a once-daily treatment for moderate to severe AD. Adverse events include folliculitis, nasopharyngitis, and headache, which are mostly mild or moderate.²¹

Final Thoughts

Topical management of pediatric AD includes traditional therapy with TCSs and newer steroid-sparing agents, which can help address corticophobia. Anticipatory guidance regarding the safety and long-term effects of individual therapies is critical to ensuring patient adherence to treatment regimens. Probiotics may help prevent pediatric AD, but future studies are needed to determine their role in treatment.

Atopic dermatitis (AD) is a chronic inflammatory skin condition associated with skin barrier impairment and immune system dysregulation.¹ Development of AD in young children can present challenges in determining appropriate treatment regimens. Natural remedies for AD often are promoted on social media over traditional treatments, including topical corticosteroids (TCSs), which can contribute to corticophobia.² Dermatologists play a critical role not only in optimizing topical therapy but also addressing patient interest in natural approaches to AD, including diet-related questions. This article outlines the role of diet and probiotics in pediatric AD and reviews the topical treatments currently approved for this patient population.

Diet and Probiotics

With a growing focus on natural therapies for AD, dietary interventions have come to the forefront. A prevalent theme among patients and their families is addressing gut health and allergic triggers. Broad elimination diets have not shown clinical benefit in patients with AD regardless of age,³ and in children, they may result in nutritional deficiencies, poor growth, and increased risk for IgE-mediated food allergies.⁴ If a true food allergy is identified based on positive IgE and an acute clinical reaction, elimination of the allergen may provide some benefit.⁵

The link between gut microbiota and skin health has driven an interest in the role of probiotics in the treatment of pediatric AD. A meta-analysis of 20 articles concluded that, whether administered to infants or breastfeeding mothers, use of probiotics overall led to a significant reduction in AD risk in infants (P=.001). Lactobacillus and mixed strains were effective.⁶ While broad elimination diets are not used to treat AD, probiotic supplementation can be considered for prevention of AD.

Topical Corticosteroids

Topical corticosteroids are the cornerstone of AD treatment; however, corticophobia among patients is on the rise, leading to poor adherence and suboptimal control of AD.⁷ Mild cutaneous adverse effects (AEs) including skin atrophy, striae, and telangiectasias may occur. Rarely, systemic AEs occur due to absorption of TCSs into the bloodstream, mainly with application of potent steroids over large body surface areas or under occlusion.⁸ When the optimal potency of a TCS is chosen and used appropriately, incidence of AEs from TCS use is very low.⁹

Counseling parents about risk factors that can lead to AEs during treatment with TCSs and formulating regimens that minimize these risks while maintaining efficacy increases adherence and outcomes. Pulse maintenance dosing of TCSs typically involves application 1 to 2 times weekly to areas of the skin that are prone to frequent outbreaks. Pulse maintenance dosing can reduce the incidence of AD flares while also decreasing the total amount of topical medication needed as compared to the reactive approach alone, thereby reducing risk for AEs.⁸

Steroid-Sparing Topical Treatments

Although TCSs are considered first-line agents, recently there has been an advent of steroid-sparing topical agents approved by the US Food and Drug Administration (FDA) for pediatric patients with AD, including topical calcineurin inhibitors (TCIs), phosphodiesterase 4 inhibitors, a Janus kinase inhibitor, and aryl hydrocarbon receptor agonists. Offering steroid-sparing agents in these patients can help ease parental anxiety regarding TCS overuse.

Topical Calcineurin Inhibitors—Pimecrolimus cream 1% and tacrolimus ointment 0.03% are approved for patients aged 2 years and older and have anti-inflammatory and antipruritic effects equivalent to low-potency TCS. Tacrolimus ­ointment 0.1% is approved for patients aged 16 years and older with similar efficacy to a midpotency TCSs. Pimecrolimus cream 1% and tacrolimus ointment 0.03% often are used off-label in ­children younger than 2 years, as supported by clinical trials showing their safety and efficacy.¹⁰ 

Topical calcineurin inhibitors can replace or supplement TCSs, making TCIs a desirable option for avoidance of steroid-related AEs. The addition of a TCI to spot treatment or a pulse regimen in a young patient can reassure them and their caregivers that the provider is proactively reducing the risk of TCS overuse. The largest barrier to TCI use is the FDA’s black box warning based on the oral formulation of tacrolimus, citing a potential increased risk for lymphoma and skin cancer; however, there is no evidence for substantial systemic absorption of topical pimecrolimus or tacrolimus.¹¹ Large task-force reviews have found no association between TCI use and development of malignancy.^12,13 Based on the current data, counseling patients and their caregivers that this risk primarily is theoretical may help them more confidently integrate TCIs into their treatment regimen. Burning and tingling may occur in a minority of pediatric patients using TCIs for AD. Applying the medication to open wounds or inflamed skin increases the risk for stinging, but pretreatment with a short course of TCSs before transitioning to a TCI may boost tolerance.¹⁴ 

Phosphodiesterase 4 Inhibitors—Crisaborole ointment 2%, a phosphodiesterase 4 inhibitor, is approved for children aged 3 months and older with mild to moderate AD. Its use has been more limited than TCSs and TCIs, as local irritation including stinging and burning can occur in up to 50% of patients.¹⁵ One study comparing crisaborole 2% with tacrolimus 0.03% revealed greater improvement with tacrolimus.¹⁶ A second phosphodiesterase 4 inhibitor approved for once-daily use in children aged 6 years and older with mild to moderate AD is roflumilast cream 0.15%. Roflumilast reduces eczema severity and pruritus, with AEs also limited to application-site stinging and burning.¹⁷ 

Janus Kinase Inhibitor—Ruxolitinib cream 1.5%, a Janus kinase inhibitor, has been approved by the FDA since 2023 for twice-daily use in children aged 12 years and older with AD. Similar to TCIs, ruxolitinib cream carries a black box warning. Short-term safety data on ruxolitinib cream have revealed low levels of ruxolitinib concentration in plasma¹⁸; however, long-term studies on topical Janus kinase inhibitors for AD in pediatric and adult populations are lacking. To reduce the risk for systemic absorption, recommendations include limiting usage to 60 g per week and limiting treatment to less than 20% of the body surface area.¹⁹ Ruxolitinib has efficacy similar to or possibly superior to triamcinolone 0.1%.²⁰ Ruxolitinib is emerging as a promising nonsteroidal option that potentially is highly efficacious and well tolerated without cutaneous AEs.  

Aryl Hydrocarbon Receptor Agonist—Tapinarof cream 1% is an aryl hydrocarbon receptor agonist that has been approved by the FDA since 2024 for children aged 2 years and older as a once-daily treatment for moderate to severe AD. Adverse events include folliculitis, nasopharyngitis, and headache, which are mostly mild or moderate.²¹

Final Thoughts

Topical management of pediatric AD includes traditional therapy with TCSs and newer steroid-sparing agents, which can help address corticophobia. Anticipatory guidance regarding the safety and long-term effects of individual therapies is critical to ensuring patient adherence to treatment regimens. Probiotics may help prevent pediatric AD, but future studies are needed to determine their role in treatment.

Hi, everyone. I’m Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

The receding of the pandemic and the understandable desire to return to normalcy has made COVID-19 vaccines a lower priority for many of our patients. However, family physicians should keep in mind that from October 1, 2024, to September 6, 2025, COVID-19 was responsible for an estimated 3.2 to 4.6 million outpatient visits, 360,000 to 520,000 hospitalizations, and 42,000 to 60,000 deaths.

In a previous commentary, I discussed the worsening disconnect between the evidence supporting the effectiveness and safety of vaccinations and increasing reluctance of patients and parents to receive them, fueled by misinformation from federal health agencies and the packing of the Advisory Committee on Immunization Practices (ACIP) with vaccine skeptics. Since then, Secretary of Health and Human Services (HHS), Robert F. Kennedy, Jr, has fired Dr Susan Monarez, his handpicked director of the CDC. This caused three senior CDC officials to resign in protest and precipitated further turmoil at the embattled agency. 

The FDA has approved 3 updated COVID-19 vaccines targeted to currently circulating strains: an mRNA vaccine from Moderna (Spikevax) for those aged 6 months or older; an mRNA vaccine from Pfizer/BioNTech (Comirnaty) for those aged ≥ 5 years; and a protein subunit vaccine from Novavax (Nuvaxovid) for those aged ≥ 12 years. However, approvals restricting the scope of these approvals to certain high-risk groups, combined with the ACIP’s recent decision to not explicitly recommend them for any group, have complicated access for many patients.

Medical groups, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists (ACOG), have published their own recommendations (Table). Of note, in opposition to the FDA and ACIP, the AAP and AAFP strongly recommend routine vaccination for children aged 6 to 23 months because they have the highest risk for hospitalization. The AAFP and ACOG both recommend COVID-19 vaccination in pregnancy to protect the pregnant patient and provide passive antibody protection to their infants up to 6 months of age. The Vaccine Integrity Project’s review of 12 safety studies published since June 2024 found that mRNA vaccines were not associated with increases in any adverse maternal or infant outcomes and had a possible protective effect against preterm birth.

In my previous commentary, 70% of Medscape readers indicated that they would follow vaccination recommendations from AAP even if they differed from CDC guidance. Administering vaccines outside of FDA labeling indications (i.e., “off label”) typically requires a physician’s prescription, which will almost certainly reduce COVID-19 vaccine uptake in children and pregnant patients, given that most people received these shots in pharmacies during the 2024-25 season. CVS and Walgreens, the country’s two largest pharmacy chains, are requiring physician prescriptions or waiting for ACIP guidance to make the new vaccines available in many states. However, an increasing number of states have implemented executive orders or passed legislation to permit pharmacists to provide vaccines to anyone who wants them. For example, the Pennsylvania State Board of Pharmacy voted unanimously to issue guidance that would allow pharmacists to administer any vaccines recommended by AAFP, AAP, or ACOG.

Erosion of vaccine uptake could easily worsen the burden of illness for our patients and the health system. Navigating the unnecessarily complex landscape of COVID-19 vaccines will be challenging, but it remains worthwhile.
 

Kenneth W. Lin, MD, MPH, Associate Director, Department of Family Medicine, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: UpToDate; American Academy of Family Physicians; Archdiocese of Washington; Association of Prevention Teaching and Research.

A version of this article appeared on Medscape.com.

Hi, everyone. I’m Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

The receding of the pandemic and the understandable desire to return to normalcy has made COVID-19 vaccines a lower priority for many of our patients. However, family physicians should keep in mind that from October 1, 2024, to September 6, 2025, COVID-19 was responsible for an estimated 3.2 to 4.6 million outpatient visits, 360,000 to 520,000 hospitalizations, and 42,000 to 60,000 deaths.

In a previous commentary, I discussed the worsening disconnect between the evidence supporting the effectiveness and safety of vaccinations and increasing reluctance of patients and parents to receive them, fueled by misinformation from federal health agencies and the packing of the Advisory Committee on Immunization Practices (ACIP) with vaccine skeptics. Since then, Secretary of Health and Human Services (HHS), Robert F. Kennedy, Jr, has fired Dr Susan Monarez, his handpicked director of the CDC. This caused three senior CDC officials to resign in protest and precipitated further turmoil at the embattled agency. 

The FDA has approved 3 updated COVID-19 vaccines targeted to currently circulating strains: an mRNA vaccine from Moderna (Spikevax) for those aged 6 months or older; an mRNA vaccine from Pfizer/BioNTech (Comirnaty) for those aged ≥ 5 years; and a protein subunit vaccine from Novavax (Nuvaxovid) for those aged ≥ 12 years. However, approvals restricting the scope of these approvals to certain high-risk groups, combined with the ACIP’s recent decision to not explicitly recommend them for any group, have complicated access for many patients.

Medical groups, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists (ACOG), have published their own recommendations (Table). Of note, in opposition to the FDA and ACIP, the AAP and AAFP strongly recommend routine vaccination for children aged 6 to 23 months because they have the highest risk for hospitalization. The AAFP and ACOG both recommend COVID-19 vaccination in pregnancy to protect the pregnant patient and provide passive antibody protection to their infants up to 6 months of age. The Vaccine Integrity Project’s review of 12 safety studies published since June 2024 found that mRNA vaccines were not associated with increases in any adverse maternal or infant outcomes and had a possible protective effect against preterm birth.

In my previous commentary, 70% of Medscape readers indicated that they would follow vaccination recommendations from AAP even if they differed from CDC guidance. Administering vaccines outside of FDA labeling indications (i.e., “off label”) typically requires a physician’s prescription, which will almost certainly reduce COVID-19 vaccine uptake in children and pregnant patients, given that most people received these shots in pharmacies during the 2024-25 season. CVS and Walgreens, the country’s two largest pharmacy chains, are requiring physician prescriptions or waiting for ACIP guidance to make the new vaccines available in many states. However, an increasing number of states have implemented executive orders or passed legislation to permit pharmacists to provide vaccines to anyone who wants them. For example, the Pennsylvania State Board of Pharmacy voted unanimously to issue guidance that would allow pharmacists to administer any vaccines recommended by AAFP, AAP, or ACOG.

Erosion of vaccine uptake could easily worsen the burden of illness for our patients and the health system. Navigating the unnecessarily complex landscape of COVID-19 vaccines will be challenging, but it remains worthwhile.
 

Kenneth W. Lin, MD, MPH, Associate Director, Department of Family Medicine, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: UpToDate; American Academy of Family Physicians; Archdiocese of Washington; Association of Prevention Teaching and Research.

A version of this article appeared on Medscape.com.

Hi, everyone. I’m Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

The receding of the pandemic and the understandable desire to return to normalcy has made COVID-19 vaccines a lower priority for many of our patients. However, family physicians should keep in mind that from October 1, 2024, to September 6, 2025, COVID-19 was responsible for an estimated 3.2 to 4.6 million outpatient visits, 360,000 to 520,000 hospitalizations, and 42,000 to 60,000 deaths.

In a previous commentary, I discussed the worsening disconnect between the evidence supporting the effectiveness and safety of vaccinations and increasing reluctance of patients and parents to receive them, fueled by misinformation from federal health agencies and the packing of the Advisory Committee on Immunization Practices (ACIP) with vaccine skeptics. Since then, Secretary of Health and Human Services (HHS), Robert F. Kennedy, Jr, has fired Dr Susan Monarez, his handpicked director of the CDC. This caused three senior CDC officials to resign in protest and precipitated further turmoil at the embattled agency. 

The FDA has approved 3 updated COVID-19 vaccines targeted to currently circulating strains: an mRNA vaccine from Moderna (Spikevax) for those aged 6 months or older; an mRNA vaccine from Pfizer/BioNTech (Comirnaty) for those aged ≥ 5 years; and a protein subunit vaccine from Novavax (Nuvaxovid) for those aged ≥ 12 years. However, approvals restricting the scope of these approvals to certain high-risk groups, combined with the ACIP’s recent decision to not explicitly recommend them for any group, have complicated access for many patients.

Medical groups, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists (ACOG), have published their own recommendations (Table). Of note, in opposition to the FDA and ACIP, the AAP and AAFP strongly recommend routine vaccination for children aged 6 to 23 months because they have the highest risk for hospitalization. The AAFP and ACOG both recommend COVID-19 vaccination in pregnancy to protect the pregnant patient and provide passive antibody protection to their infants up to 6 months of age. The Vaccine Integrity Project’s review of 12 safety studies published since June 2024 found that mRNA vaccines were not associated with increases in any adverse maternal or infant outcomes and had a possible protective effect against preterm birth.

In my previous commentary, 70% of Medscape readers indicated that they would follow vaccination recommendations from AAP even if they differed from CDC guidance. Administering vaccines outside of FDA labeling indications (i.e., “off label”) typically requires a physician’s prescription, which will almost certainly reduce COVID-19 vaccine uptake in children and pregnant patients, given that most people received these shots in pharmacies during the 2024-25 season. CVS and Walgreens, the country’s two largest pharmacy chains, are requiring physician prescriptions or waiting for ACIP guidance to make the new vaccines available in many states. However, an increasing number of states have implemented executive orders or passed legislation to permit pharmacists to provide vaccines to anyone who wants them. For example, the Pennsylvania State Board of Pharmacy voted unanimously to issue guidance that would allow pharmacists to administer any vaccines recommended by AAFP, AAP, or ACOG.

Erosion of vaccine uptake could easily worsen the burden of illness for our patients and the health system. Navigating the unnecessarily complex landscape of COVID-19 vaccines will be challenging, but it remains worthwhile.
 

Kenneth W. Lin, MD, MPH, Associate Director, Department of Family Medicine, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: UpToDate; American Academy of Family Physicians; Archdiocese of Washington; Association of Prevention Teaching and Research.

A version of this article appeared on Medscape.com.

In this Practical AI column, we’ve explored everything from large language models to the nuances of trial matching, but one of the most immediate and impactful applications of AI is unfolding right now in breast imaging. For oncologists, this isn’t an abstract future — with new screening guidelines, dense-breast mandates, and a shrinking radiology workforce, it’s the imaging reports and patient questions landing in your clinic today.

Here is what oncologists need to know, and how to put it to work for their patients.

 

Why AI in Mammography Matters

More than 200 million women undergo breast cancer screening each year. In the US alone, 10% of the 40 million women screened annually require additional diagnostic imaging, and 4%–5% of these women are eventually diagnosed with breast cancer.

Two major shifts are redefining breast cancer screening in the US: The US Preventive Services Task Force (USPSTF) now recommends biennial screening from age 40 to 74 years, and notifying patients of breast density is a federal requirement as of September 10, 2024. That means more mammograms, more patient questions, and more downstream oncology decisions. Patients will increasingly ask about “dense” breast results and what to do next. Add a national radiologist shortage into the mix, and the pressure on timely callbacks, biopsies, and treatment planning will only grow.

 

Can AI Help Without Compromising Care?

The short answer is yes. With AI, we may be able to transform these rate-limiting steps into opportunities for earlier detection, decentralized screening, and smarter triage and save hundreds of thousands of women from an unnecessary diagnostic procedure, if implemented deliberately.

Don’t Confuse Today’s AI With Yesterday’s CAD 

Think of older computer-aided detection (CAD) like a 1990s chemotherapy drug: It sometimes helped, but it came with significant toxicity and rarely delivered consistent survival benefits. Today’s deep-learning AI is closer to targeted therapy — trained on millions of “trial participants” (mammograms), more precise, and applied in specific contexts where it adds value. If you once dismissed CAD as noise, it’s time to revisit what AI can now offer.

The role of AI is broader than drawing boxes. It provides second readings, worklist triage, risk prediction, density assessment, and decision support. FDA has cleared several AI tools for both 2D and digital breast tomosynthesis (DBT), which include iCAD ProFound (DBT), ScreenPoint Transpara (2D/DBT), and Lunit INSIGHT DBT. 

Some of the strongest evidence for AI in mammography is as a second reader during screening. Large trials show that AI plus one radiologist can match reading from two radiologists, cutting workload by about 40%. For example, the MASAI randomized trial showed that AI-supported screening achieved similar cancer detection but cut human screen-reading workload about 44% vs standard double reading (39,996 vs 40,024 participants). The primary interval cancer outcomes are maturing, but the safety analysis is reassuring.

Reducing second reads and arbitration time are important for clinicians because it frees capacity for callbacks and diagnostic workups. This will be especially key given that screening now starts at age 40. That will mean about 21 to 22 million more women are newly eligible, translating to about 10 to 11 million additional mammograms each year under biennial screening.

Another important area where AI can make its mark in mammography is triage and time to diagnosis. The results from a randomized implementation study showed that AI-prioritized worklists accelerated time to additional imaging and biopsy diagnosis without harming efficiency for others — exactly the kind of outcome patients feel.

Multiple studies have demonstrated improved diagnostic performance and shorter reading times when AI supports DBT interpretation, which is important because DBT can otherwise be time intensive.

We are also seeing rapid advancement in risk-based screening, moving beyond a single dense vs not dense approach. Deep-learning risk models, such as Mirai, predict 1- to 5-year breast cancer risk directly from the mammogram, and these tools are now being assessed prospectively to guide supplemental MRI. Cost-effectiveness modeling supports risk-stratified intervals vs one-size-fits-all schedules.

Finally, automated density tools, such as Transpara Density and Volpara, offer objective, reproducible volumetric measures that map to the Breast Imaging-Reporting and Data System, which is useful for Mammography Quality Standards Act-required reporting and as inputs to risk calculators.

While early evidence suggests AI may help surface future or interval cancers earlier, including more invasive tumors, the definitive impacts on interval cancer rates and mortality require longitudinal follow-up, which is now in progress.

 

Pitfalls to Watch For

Bias is real. Studies show false-positive differences by race, age, and density. AI can even infer racial identity from images, potentially amplifying disparities. Performance can also shift by vendor, demographics, and prevalence.

A Radiology study of 4855 DBT exams showed that an algorithm produced more false-positive case scores in Black patients and older patients (aged 71-80 years) patients and in women with extremely dense breasts. This can happen because AI can infer proxies for race directly from images, even when humans cannot, and this can propagate disparities if not addressed. External validations and reviews emphasize that performance can shift with device manufacturer, demographics, and prevalence, which is why all tools need to undergo local validation and calibration. 

Here’s a pragmatic adoption checklist before going live with an AI tool.

• Confirm FDA clearance: Verify the name and version of the algorithm, imaging modes (2D vs DBT), and operating points. Confirm 510(k) numbers.
• Local validation: Test on your patient mix and vendor stack (Hologic, GE, Siemens, Fuji). Compare this to your baseline recall rate, positive predictive value of recall (PPV1), cancer detection rate, and reading time. Commit to recalibration if drift occurs.
• Equity plan: Monitor false-positive and negative false-rates by age, race/ethnicity, and density; document corrective actions if disparities emerge. (This isn’t optional.)
• Workflow clarity: Is AI a second reader, an additional reader, or a triage tool? Who arbitrates discordance? What’s the escalation path for high-risk or interval cancer-like patterns?
• Regulatory strategy: Confirm whether the vendor has (or will file) a Predetermined Change Control Plan so models can be updated safely without repeated submissions. Also confirm how you’ll be notified about performance-relevant changes.
• Data governance: Audit logs of AI outputs, retention, protected health information handling, and the patient communication policy for AI-assisted reads.

After going live, set up a quarterly dashboard. It should include cancer detection rate per 1000 patients, recall rate, PPV1, interval cancer rate (as it matures), reading time, and turnaround time to diagnostic imaging or biopsy — all stratified by age, race/ethnicity, and density.

Here, I dissect what this discussion means through the lens of Moravec’s paradox (machines excel at what clinicians find hard, and vice versa) and offer a possible playbook for putting these tools to work.

 

What to Tell Patients

When speaking with patients, emphasize that a radiologist still reads their mammogram. AI helps with consistency and efficiency; it doesn’t replace human oversight. Patients with dense breasts should still expect a standard notice; discussion of individualized risk factors, such as family history, genetics, and prior biopsies; and consideration of supplemental imaging if risk warrants. But it’s also important to tell these patients that while dense breasts are common, they do not automatically mean high cancer risk.

As for screening schedules, remind patients that screening is at least biennial from 40 to 74 years of age per the USPSTF guidelines; however, specialty groups may recommend starting on an annual schedule at 40.

 

What You Can Implement Now

There are multiple practical use cases you can introduce now. One is to use AI as a second reader or an additional reader safety net to preserve detection while reducing human workload. This helps your breast center absorb screening expansion to age 40 without diluting quality. Another is to turn on AI triage to shorten the time to callback and biopsy for the few who need it most — patients notice and appreciate faster answers. You can also begin adopting automated density plus risk models to move beyond “dense/not dense.” For selected patients, AI-informed risk can justify MRI or tailored intervals. 

Here’s a quick cheat sheet (for your next leadership or tumor-board meeting).

 

Do:

• Use AI as a second or additional reader or triage tool, not as a black box.
• Track cancer detection rate, recall, PPV1, interval cancers, and reading time, stratified by age, race, and breast density.
• Pair automated density with AI risk to personalize screening and supplemental imaging.
• Enroll patients in future clinical trials, such as PRISM, the first large-scale randomized controlled trial of AI for screening mammography. This US-based, $16 million, seven-site study is funded by the Patient-Centered Outcomes Research Institute.

Don’t:

• Assume “AI = CAD.” The 2015 CAD story is over; modern deep learning systems are different and require different oversight.
• Go live without a local validation and equity plan or without clarity on software updates.
• Forget to remind patients that screening starts at age 40, and dense breast notifications are now universal. Use the visit to discuss risk, supplemental imaging, and why a human still directs their care.

The Bottom Line

AI won’t replace radiologists or read mammograms for us — just as PET scans didn’t replace oncologists and stethoscopes didn’t make cardiologists obsolete. What it will do is catch what the tired human eye might miss, shave days off anxious waiting, and turn breast density into data instead of doubt. For oncologists, that means staging sooner, enrolling smarter, and spending more time talking with patients instead of chasing callbacks.

In short, AI may not take the picture, but it helps us frame the story, making it sharper, faster, and with fewer blind spots. By pairing this powerful technology with rigorous, equity-focused local validation and transparent governance under the FDA’s emerging Predetermined Change Control Plan framework, we can realize the tangible benefits of practical AI for our patients without widening disparities. 

Now, during Breast Cancer Awareness Month, how about we add on AI to that pink ribbon — how cool would that be?

Thoughts? Drop me a line at [email protected]. Let’s keep the conversation — and pink ribbons — going.

Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical AI officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as Systemwide Chief of Hematology and Oncology at St. Luke’s University Health Network, where he maintains a connection to patient care by attending to patients 2 days a week.

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

In this Practical AI column, we’ve explored everything from large language models to the nuances of trial matching, but one of the most immediate and impactful applications of AI is unfolding right now in breast imaging. For oncologists, this isn’t an abstract future — with new screening guidelines, dense-breast mandates, and a shrinking radiology workforce, it’s the imaging reports and patient questions landing in your clinic today.

Here is what oncologists need to know, and how to put it to work for their patients.

 

Why AI in Mammography Matters

More than 200 million women undergo breast cancer screening each year. In the US alone, 10% of the 40 million women screened annually require additional diagnostic imaging, and 4%–5% of these women are eventually diagnosed with breast cancer.

Two major shifts are redefining breast cancer screening in the US: The US Preventive Services Task Force (USPSTF) now recommends biennial screening from age 40 to 74 years, and notifying patients of breast density is a federal requirement as of September 10, 2024. That means more mammograms, more patient questions, and more downstream oncology decisions. Patients will increasingly ask about “dense” breast results and what to do next. Add a national radiologist shortage into the mix, and the pressure on timely callbacks, biopsies, and treatment planning will only grow.

 

Can AI Help Without Compromising Care?

The short answer is yes. With AI, we may be able to transform these rate-limiting steps into opportunities for earlier detection, decentralized screening, and smarter triage and save hundreds of thousands of women from an unnecessary diagnostic procedure, if implemented deliberately.

Don’t Confuse Today’s AI With Yesterday’s CAD 

Think of older computer-aided detection (CAD) like a 1990s chemotherapy drug: It sometimes helped, but it came with significant toxicity and rarely delivered consistent survival benefits. Today’s deep-learning AI is closer to targeted therapy — trained on millions of “trial participants” (mammograms), more precise, and applied in specific contexts where it adds value. If you once dismissed CAD as noise, it’s time to revisit what AI can now offer.

The role of AI is broader than drawing boxes. It provides second readings, worklist triage, risk prediction, density assessment, and decision support. FDA has cleared several AI tools for both 2D and digital breast tomosynthesis (DBT), which include iCAD ProFound (DBT), ScreenPoint Transpara (2D/DBT), and Lunit INSIGHT DBT. 

Some of the strongest evidence for AI in mammography is as a second reader during screening. Large trials show that AI plus one radiologist can match reading from two radiologists, cutting workload by about 40%. For example, the MASAI randomized trial showed that AI-supported screening achieved similar cancer detection but cut human screen-reading workload about 44% vs standard double reading (39,996 vs 40,024 participants). The primary interval cancer outcomes are maturing, but the safety analysis is reassuring.

Reducing second reads and arbitration time are important for clinicians because it frees capacity for callbacks and diagnostic workups. This will be especially key given that screening now starts at age 40. That will mean about 21 to 22 million more women are newly eligible, translating to about 10 to 11 million additional mammograms each year under biennial screening.

Another important area where AI can make its mark in mammography is triage and time to diagnosis. The results from a randomized implementation study showed that AI-prioritized worklists accelerated time to additional imaging and biopsy diagnosis without harming efficiency for others — exactly the kind of outcome patients feel.

Multiple studies have demonstrated improved diagnostic performance and shorter reading times when AI supports DBT interpretation, which is important because DBT can otherwise be time intensive.

We are also seeing rapid advancement in risk-based screening, moving beyond a single dense vs not dense approach. Deep-learning risk models, such as Mirai, predict 1- to 5-year breast cancer risk directly from the mammogram, and these tools are now being assessed prospectively to guide supplemental MRI. Cost-effectiveness modeling supports risk-stratified intervals vs one-size-fits-all schedules.

Finally, automated density tools, such as Transpara Density and Volpara, offer objective, reproducible volumetric measures that map to the Breast Imaging-Reporting and Data System, which is useful for Mammography Quality Standards Act-required reporting and as inputs to risk calculators.

While early evidence suggests AI may help surface future or interval cancers earlier, including more invasive tumors, the definitive impacts on interval cancer rates and mortality require longitudinal follow-up, which is now in progress.

 

Pitfalls to Watch For

Bias is real. Studies show false-positive differences by race, age, and density. AI can even infer racial identity from images, potentially amplifying disparities. Performance can also shift by vendor, demographics, and prevalence.

A Radiology study of 4855 DBT exams showed that an algorithm produced more false-positive case scores in Black patients and older patients (aged 71-80 years) patients and in women with extremely dense breasts. This can happen because AI can infer proxies for race directly from images, even when humans cannot, and this can propagate disparities if not addressed. External validations and reviews emphasize that performance can shift with device manufacturer, demographics, and prevalence, which is why all tools need to undergo local validation and calibration. 

Here’s a pragmatic adoption checklist before going live with an AI tool.

• Confirm FDA clearance: Verify the name and version of the algorithm, imaging modes (2D vs DBT), and operating points. Confirm 510(k) numbers.
• Local validation: Test on your patient mix and vendor stack (Hologic, GE, Siemens, Fuji). Compare this to your baseline recall rate, positive predictive value of recall (PPV1), cancer detection rate, and reading time. Commit to recalibration if drift occurs.
• Equity plan: Monitor false-positive and negative false-rates by age, race/ethnicity, and density; document corrective actions if disparities emerge. (This isn’t optional.)
• Workflow clarity: Is AI a second reader, an additional reader, or a triage tool? Who arbitrates discordance? What’s the escalation path for high-risk or interval cancer-like patterns?
• Regulatory strategy: Confirm whether the vendor has (or will file) a Predetermined Change Control Plan so models can be updated safely without repeated submissions. Also confirm how you’ll be notified about performance-relevant changes.
• Data governance: Audit logs of AI outputs, retention, protected health information handling, and the patient communication policy for AI-assisted reads.

After going live, set up a quarterly dashboard. It should include cancer detection rate per 1000 patients, recall rate, PPV1, interval cancer rate (as it matures), reading time, and turnaround time to diagnostic imaging or biopsy — all stratified by age, race/ethnicity, and density.

Here, I dissect what this discussion means through the lens of Moravec’s paradox (machines excel at what clinicians find hard, and vice versa) and offer a possible playbook for putting these tools to work.

 

What to Tell Patients

When speaking with patients, emphasize that a radiologist still reads their mammogram. AI helps with consistency and efficiency; it doesn’t replace human oversight. Patients with dense breasts should still expect a standard notice; discussion of individualized risk factors, such as family history, genetics, and prior biopsies; and consideration of supplemental imaging if risk warrants. But it’s also important to tell these patients that while dense breasts are common, they do not automatically mean high cancer risk.

As for screening schedules, remind patients that screening is at least biennial from 40 to 74 years of age per the USPSTF guidelines; however, specialty groups may recommend starting on an annual schedule at 40.

 

What You Can Implement Now

There are multiple practical use cases you can introduce now. One is to use AI as a second reader or an additional reader safety net to preserve detection while reducing human workload. This helps your breast center absorb screening expansion to age 40 without diluting quality. Another is to turn on AI triage to shorten the time to callback and biopsy for the few who need it most — patients notice and appreciate faster answers. You can also begin adopting automated density plus risk models to move beyond “dense/not dense.” For selected patients, AI-informed risk can justify MRI or tailored intervals. 

Here’s a quick cheat sheet (for your next leadership or tumor-board meeting).

 

Do:

• Use AI as a second or additional reader or triage tool, not as a black box.
• Track cancer detection rate, recall, PPV1, interval cancers, and reading time, stratified by age, race, and breast density.
• Pair automated density with AI risk to personalize screening and supplemental imaging.
• Enroll patients in future clinical trials, such as PRISM, the first large-scale randomized controlled trial of AI for screening mammography. This US-based, $16 million, seven-site study is funded by the Patient-Centered Outcomes Research Institute.

Don’t:

• Assume “AI = CAD.” The 2015 CAD story is over; modern deep learning systems are different and require different oversight.
• Go live without a local validation and equity plan or without clarity on software updates.
• Forget to remind patients that screening starts at age 40, and dense breast notifications are now universal. Use the visit to discuss risk, supplemental imaging, and why a human still directs their care.

The Bottom Line

AI won’t replace radiologists or read mammograms for us — just as PET scans didn’t replace oncologists and stethoscopes didn’t make cardiologists obsolete. What it will do is catch what the tired human eye might miss, shave days off anxious waiting, and turn breast density into data instead of doubt. For oncologists, that means staging sooner, enrolling smarter, and spending more time talking with patients instead of chasing callbacks.

In short, AI may not take the picture, but it helps us frame the story, making it sharper, faster, and with fewer blind spots. By pairing this powerful technology with rigorous, equity-focused local validation and transparent governance under the FDA’s emerging Predetermined Change Control Plan framework, we can realize the tangible benefits of practical AI for our patients without widening disparities. 

Now, during Breast Cancer Awareness Month, how about we add on AI to that pink ribbon — how cool would that be?

Thoughts? Drop me a line at [email protected]. Let’s keep the conversation — and pink ribbons — going.

Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical AI officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as Systemwide Chief of Hematology and Oncology at St. Luke’s University Health Network, where he maintains a connection to patient care by attending to patients 2 days a week.

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

In this Practical AI column, we’ve explored everything from large language models to the nuances of trial matching, but one of the most immediate and impactful applications of AI is unfolding right now in breast imaging. For oncologists, this isn’t an abstract future — with new screening guidelines, dense-breast mandates, and a shrinking radiology workforce, it’s the imaging reports and patient questions landing in your clinic today.

Here is what oncologists need to know, and how to put it to work for their patients.

 

Why AI in Mammography Matters

More than 200 million women undergo breast cancer screening each year. In the US alone, 10% of the 40 million women screened annually require additional diagnostic imaging, and 4%–5% of these women are eventually diagnosed with breast cancer.

Two major shifts are redefining breast cancer screening in the US: The US Preventive Services Task Force (USPSTF) now recommends biennial screening from age 40 to 74 years, and notifying patients of breast density is a federal requirement as of September 10, 2024. That means more mammograms, more patient questions, and more downstream oncology decisions. Patients will increasingly ask about “dense” breast results and what to do next. Add a national radiologist shortage into the mix, and the pressure on timely callbacks, biopsies, and treatment planning will only grow.

 

Can AI Help Without Compromising Care?

The short answer is yes. With AI, we may be able to transform these rate-limiting steps into opportunities for earlier detection, decentralized screening, and smarter triage and save hundreds of thousands of women from an unnecessary diagnostic procedure, if implemented deliberately.

Don’t Confuse Today’s AI With Yesterday’s CAD 

Think of older computer-aided detection (CAD) like a 1990s chemotherapy drug: It sometimes helped, but it came with significant toxicity and rarely delivered consistent survival benefits. Today’s deep-learning AI is closer to targeted therapy — trained on millions of “trial participants” (mammograms), more precise, and applied in specific contexts where it adds value. If you once dismissed CAD as noise, it’s time to revisit what AI can now offer.

The role of AI is broader than drawing boxes. It provides second readings, worklist triage, risk prediction, density assessment, and decision support. FDA has cleared several AI tools for both 2D and digital breast tomosynthesis (DBT), which include iCAD ProFound (DBT), ScreenPoint Transpara (2D/DBT), and Lunit INSIGHT DBT. 

Some of the strongest evidence for AI in mammography is as a second reader during screening. Large trials show that AI plus one radiologist can match reading from two radiologists, cutting workload by about 40%. For example, the MASAI randomized trial showed that AI-supported screening achieved similar cancer detection but cut human screen-reading workload about 44% vs standard double reading (39,996 vs 40,024 participants). The primary interval cancer outcomes are maturing, but the safety analysis is reassuring.

Reducing second reads and arbitration time are important for clinicians because it frees capacity for callbacks and diagnostic workups. This will be especially key given that screening now starts at age 40. That will mean about 21 to 22 million more women are newly eligible, translating to about 10 to 11 million additional mammograms each year under biennial screening.

Another important area where AI can make its mark in mammography is triage and time to diagnosis. The results from a randomized implementation study showed that AI-prioritized worklists accelerated time to additional imaging and biopsy diagnosis without harming efficiency for others — exactly the kind of outcome patients feel.

Multiple studies have demonstrated improved diagnostic performance and shorter reading times when AI supports DBT interpretation, which is important because DBT can otherwise be time intensive.

We are also seeing rapid advancement in risk-based screening, moving beyond a single dense vs not dense approach. Deep-learning risk models, such as Mirai, predict 1- to 5-year breast cancer risk directly from the mammogram, and these tools are now being assessed prospectively to guide supplemental MRI. Cost-effectiveness modeling supports risk-stratified intervals vs one-size-fits-all schedules.

Finally, automated density tools, such as Transpara Density and Volpara, offer objective, reproducible volumetric measures that map to the Breast Imaging-Reporting and Data System, which is useful for Mammography Quality Standards Act-required reporting and as inputs to risk calculators.

While early evidence suggests AI may help surface future or interval cancers earlier, including more invasive tumors, the definitive impacts on interval cancer rates and mortality require longitudinal follow-up, which is now in progress.

 

Pitfalls to Watch For

Bias is real. Studies show false-positive differences by race, age, and density. AI can even infer racial identity from images, potentially amplifying disparities. Performance can also shift by vendor, demographics, and prevalence.

A Radiology study of 4855 DBT exams showed that an algorithm produced more false-positive case scores in Black patients and older patients (aged 71-80 years) patients and in women with extremely dense breasts. This can happen because AI can infer proxies for race directly from images, even when humans cannot, and this can propagate disparities if not addressed. External validations and reviews emphasize that performance can shift with device manufacturer, demographics, and prevalence, which is why all tools need to undergo local validation and calibration. 

Here’s a pragmatic adoption checklist before going live with an AI tool.

• Confirm FDA clearance: Verify the name and version of the algorithm, imaging modes (2D vs DBT), and operating points. Confirm 510(k) numbers.
• Local validation: Test on your patient mix and vendor stack (Hologic, GE, Siemens, Fuji). Compare this to your baseline recall rate, positive predictive value of recall (PPV1), cancer detection rate, and reading time. Commit to recalibration if drift occurs.
• Equity plan: Monitor false-positive and negative false-rates by age, race/ethnicity, and density; document corrective actions if disparities emerge. (This isn’t optional.)
• Workflow clarity: Is AI a second reader, an additional reader, or a triage tool? Who arbitrates discordance? What’s the escalation path for high-risk or interval cancer-like patterns?
• Regulatory strategy: Confirm whether the vendor has (or will file) a Predetermined Change Control Plan so models can be updated safely without repeated submissions. Also confirm how you’ll be notified about performance-relevant changes.
• Data governance: Audit logs of AI outputs, retention, protected health information handling, and the patient communication policy for AI-assisted reads.

After going live, set up a quarterly dashboard. It should include cancer detection rate per 1000 patients, recall rate, PPV1, interval cancer rate (as it matures), reading time, and turnaround time to diagnostic imaging or biopsy — all stratified by age, race/ethnicity, and density.

Here, I dissect what this discussion means through the lens of Moravec’s paradox (machines excel at what clinicians find hard, and vice versa) and offer a possible playbook for putting these tools to work.

 

What to Tell Patients

When speaking with patients, emphasize that a radiologist still reads their mammogram. AI helps with consistency and efficiency; it doesn’t replace human oversight. Patients with dense breasts should still expect a standard notice; discussion of individualized risk factors, such as family history, genetics, and prior biopsies; and consideration of supplemental imaging if risk warrants. But it’s also important to tell these patients that while dense breasts are common, they do not automatically mean high cancer risk.

As for screening schedules, remind patients that screening is at least biennial from 40 to 74 years of age per the USPSTF guidelines; however, specialty groups may recommend starting on an annual schedule at 40.

 

What You Can Implement Now

There are multiple practical use cases you can introduce now. One is to use AI as a second reader or an additional reader safety net to preserve detection while reducing human workload. This helps your breast center absorb screening expansion to age 40 without diluting quality. Another is to turn on AI triage to shorten the time to callback and biopsy for the few who need it most — patients notice and appreciate faster answers. You can also begin adopting automated density plus risk models to move beyond “dense/not dense.” For selected patients, AI-informed risk can justify MRI or tailored intervals. 

Here’s a quick cheat sheet (for your next leadership or tumor-board meeting).

 

Do:

• Use AI as a second or additional reader or triage tool, not as a black box.
• Track cancer detection rate, recall, PPV1, interval cancers, and reading time, stratified by age, race, and breast density.
• Pair automated density with AI risk to personalize screening and supplemental imaging.
• Enroll patients in future clinical trials, such as PRISM, the first large-scale randomized controlled trial of AI for screening mammography. This US-based, $16 million, seven-site study is funded by the Patient-Centered Outcomes Research Institute.

Don’t:

• Assume “AI = CAD.” The 2015 CAD story is over; modern deep learning systems are different and require different oversight.
• Go live without a local validation and equity plan or without clarity on software updates.
• Forget to remind patients that screening starts at age 40, and dense breast notifications are now universal. Use the visit to discuss risk, supplemental imaging, and why a human still directs their care.

The Bottom Line

AI won’t replace radiologists or read mammograms for us — just as PET scans didn’t replace oncologists and stethoscopes didn’t make cardiologists obsolete. What it will do is catch what the tired human eye might miss, shave days off anxious waiting, and turn breast density into data instead of doubt. For oncologists, that means staging sooner, enrolling smarter, and spending more time talking with patients instead of chasing callbacks.

In short, AI may not take the picture, but it helps us frame the story, making it sharper, faster, and with fewer blind spots. By pairing this powerful technology with rigorous, equity-focused local validation and transparent governance under the FDA’s emerging Predetermined Change Control Plan framework, we can realize the tangible benefits of practical AI for our patients without widening disparities. 

Now, during Breast Cancer Awareness Month, how about we add on AI to that pink ribbon — how cool would that be?

Thoughts? Drop me a line at [email protected]. Let’s keep the conversation — and pink ribbons — going.

Arturo Loaiza-Bonilla, MD, MSEd, is the co-founder and chief medical AI officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr Loaiza-Bonilla serves as Systemwide Chief of Hematology and Oncology at St. Luke’s University Health Network, where he maintains a connection to patient care by attending to patients 2 days a week.

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