Breast Cancer

In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.

The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.

“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.

While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.

“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
 

Estimating the pandemic’s impact on cancer care

While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.

There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.

But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”

With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.

A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.

“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.

Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.

While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.

More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks. 
 

Will COVID-19 exacerbate racial disparities in cancer?

Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.

“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.

There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.

“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”

But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”

In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.

“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”

To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages  to “specific populations, cultural groups and languages”.

But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”

“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”

Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.

“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
 

Building trust

All the panelists agreed that building trust with the public will be key to getting cancer care back on track.  

“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.

For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.

“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”

Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.

Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”

This article first appeared on Medscape.com.

In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.

The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.

“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.

While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.

“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
 

Estimating the pandemic’s impact on cancer care

While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.

There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.

But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”

With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.

A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.

“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.

Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.

While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.

More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks. 
 

Will COVID-19 exacerbate racial disparities in cancer?

Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.

“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.

There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.

“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”

But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”

In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.

“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”

To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages  to “specific populations, cultural groups and languages”.

But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”

“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”

Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.

“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
 

Building trust

All the panelists agreed that building trust with the public will be key to getting cancer care back on track.  

“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.

For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.

“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”

Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.

Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”

This article first appeared on Medscape.com.

In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.

The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.

“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.

While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.

“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
 

Estimating the pandemic’s impact on cancer care

While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.

There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.

But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”

With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.

A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.

“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.

Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.

While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.

More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks. 
 

Will COVID-19 exacerbate racial disparities in cancer?

Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.

“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.

There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.

“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”

But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”

In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.

“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”

To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages  to “specific populations, cultural groups and languages”.

But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”

“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”

Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.

“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
 

Building trust

All the panelists agreed that building trust with the public will be key to getting cancer care back on track.  

“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.

For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.

“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”

Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.

Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”

This article first appeared on Medscape.com.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the baseline exam, according to a review of nearly 1.6 million screenings.

At baseline, DBT improved recall and cancer detection rates for all women. On subsequent exams, differences in screening performance between DBT and DM varied by age and density subgroups. However, there were no significant differences in recall or cancer detection rates among women with extremely dense breasts in any age group.

Kathryn Lowry, MD, of the University of Washington in Seattle, and colleagues reported these findings in JAMA Network Open.

“Our findings suggest that density likely should not be used as a criterion to triage use of DBT for routine screening in settings where DBT is not universally available, as has been reported in physician surveys,” the authors wrote. “The largest absolute improvements of DBT screening were achieved on the baseline screening examination, suggesting that women presenting for their first screening examination are particularly important to prioritize for DBT,” regardless of breast density or age.
 

Study details

Dr. Lowry and colleagues reviewed 1,584,079 screenings in women aged 40-79 years. The exams were done from January 2010 to April 2018 at Breast Cancer Surveillance Consortium facilities across the United States.

Sixty-five percent of the exams were in White, non-Hispanic women, 25.2% were in women younger than 50 years, and 42.4% were in women with heterogeneously dense or extremely dense breasts. Subjects had no history of breast cancer, mastectomy, or breast augmentation.

The investigators compared the performance of 1,273,492 DMs with 310,587 DBTs across the four Breast Imaging Reporting and Database System density types: almost entirely fatty, scattered fibroglandular density, heterogeneously dense, and extremely dense.

Findings were adjusted for race, family breast cancer history, and other potential confounders.
 

Recall and cancer detection rates

At baseline, recall and cancer detection rates were better with DBT than with DM, regardless of breast density subtype or patient age.

For instance, in women aged 50-59 years, screening recalls per 1,000 exams dropped from 241 with DM to 204 with DBT (relative risk, 0.84; 95% confidence interval, 0.73-0.98). Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT (RR, 1.50; 95% CI, 1.10-2.08).

On follow-up exams, recall rates were lower with DBT for women with scattered fibroglandular density and heterogeneously dense breasts in all age groups, as well as in women with almost entirely fatty breasts aged 50-79 years.

“By contrast, there were no significant differences in recall rates in women with extremely dense breasts in any age group,” the authors wrote.

Cancer detection rates on follow-up exams varied by age and breast density.

Cancer detection rates were higher with DBT than with DM in women with heterogeneously dense breasts in all age groups and in women with scattered fibroglandular density at 50-59 years of age and 60-79 years of age. However, cancer detection rates were not significantly different with DBT or DM for women with almost entirely fatty breasts or extremely dense breasts of any age.
 

Implications and next steps

Dr. Lowry and colleagues noted that use of DBT has increased steadily since it was approved by the Food and Drug Administration in 2011, driven by studies demonstrating, among other things, earlier detection of invasive cancers.

The problem has been that previous investigations “largely dichotomized dense (heterogeneously dense and extremely dense) and nondense (almost entirely fat and scattered fibroglandular densities) categories,” the authors wrote. Therefore, the nuance of benefit across density subtypes hasn’t been clear.

The finding that “screening benefits of DBT differ for women with heterogeneously dense breasts [versus] extremely dense breasts is especially important in the current landscape of density legislation and demand for supplemental screening tests beyond mammography. To date, most state mandates and ... proposed federal legislation have uniformly grouped women with heterogeneously dense breasts and those with extremely dense breasts as a single population,” the authors wrote.

As the new findings suggest, “there are important differences in performance that may not be appreciated by combining density categories,” the authors added.

The results “suggest that women with extremely dense breast tissue may benefit more from additional screening than women with heterogeneously dense breasts who undergo tomosynthesis mammography,” Catherine Tuite, MD, of Fox Chase Cancer Center in Philadelphia, and colleagues wrote in a related editorial.

“Research to determine density and risk-specific outcomes for supplemental screening methods, such as magnetic resonance imaging ... molecular breast imaging, or ultrasonography is necessary to understand which screening method beyond DBT is best for average-risk women with heterogeneous or extremely dense breasts,” the editorialists wrote.

This research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. Dr. Lowry reported grants from GE Healthcare outside the submitted work. The editorialists didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.

In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the baseline exam, according to a review of nearly 1.6 million screenings.

At baseline, DBT improved recall and cancer detection rates for all women. On subsequent exams, differences in screening performance between DBT and DM varied by age and density subgroups. However, there were no significant differences in recall or cancer detection rates among women with extremely dense breasts in any age group.

Kathryn Lowry, MD, of the University of Washington in Seattle, and colleagues reported these findings in JAMA Network Open.

“Our findings suggest that density likely should not be used as a criterion to triage use of DBT for routine screening in settings where DBT is not universally available, as has been reported in physician surveys,” the authors wrote. “The largest absolute improvements of DBT screening were achieved on the baseline screening examination, suggesting that women presenting for their first screening examination are particularly important to prioritize for DBT,” regardless of breast density or age.
 

Study details

Dr. Lowry and colleagues reviewed 1,584,079 screenings in women aged 40-79 years. The exams were done from January 2010 to April 2018 at Breast Cancer Surveillance Consortium facilities across the United States.

Sixty-five percent of the exams were in White, non-Hispanic women, 25.2% were in women younger than 50 years, and 42.4% were in women with heterogeneously dense or extremely dense breasts. Subjects had no history of breast cancer, mastectomy, or breast augmentation.

The investigators compared the performance of 1,273,492 DMs with 310,587 DBTs across the four Breast Imaging Reporting and Database System density types: almost entirely fatty, scattered fibroglandular density, heterogeneously dense, and extremely dense.

Findings were adjusted for race, family breast cancer history, and other potential confounders.
 

Recall and cancer detection rates

At baseline, recall and cancer detection rates were better with DBT than with DM, regardless of breast density subtype or patient age.

For instance, in women aged 50-59 years, screening recalls per 1,000 exams dropped from 241 with DM to 204 with DBT (relative risk, 0.84; 95% confidence interval, 0.73-0.98). Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT (RR, 1.50; 95% CI, 1.10-2.08).

On follow-up exams, recall rates were lower with DBT for women with scattered fibroglandular density and heterogeneously dense breasts in all age groups, as well as in women with almost entirely fatty breasts aged 50-79 years.

“By contrast, there were no significant differences in recall rates in women with extremely dense breasts in any age group,” the authors wrote.

Cancer detection rates on follow-up exams varied by age and breast density.

Cancer detection rates were higher with DBT than with DM in women with heterogeneously dense breasts in all age groups and in women with scattered fibroglandular density at 50-59 years of age and 60-79 years of age. However, cancer detection rates were not significantly different with DBT or DM for women with almost entirely fatty breasts or extremely dense breasts of any age.
 

Implications and next steps

Dr. Lowry and colleagues noted that use of DBT has increased steadily since it was approved by the Food and Drug Administration in 2011, driven by studies demonstrating, among other things, earlier detection of invasive cancers.

The problem has been that previous investigations “largely dichotomized dense (heterogeneously dense and extremely dense) and nondense (almost entirely fat and scattered fibroglandular densities) categories,” the authors wrote. Therefore, the nuance of benefit across density subtypes hasn’t been clear.

The finding that “screening benefits of DBT differ for women with heterogeneously dense breasts [versus] extremely dense breasts is especially important in the current landscape of density legislation and demand for supplemental screening tests beyond mammography. To date, most state mandates and ... proposed federal legislation have uniformly grouped women with heterogeneously dense breasts and those with extremely dense breasts as a single population,” the authors wrote.

As the new findings suggest, “there are important differences in performance that may not be appreciated by combining density categories,” the authors added.

The results “suggest that women with extremely dense breast tissue may benefit more from additional screening than women with heterogeneously dense breasts who undergo tomosynthesis mammography,” Catherine Tuite, MD, of Fox Chase Cancer Center in Philadelphia, and colleagues wrote in a related editorial.

“Research to determine density and risk-specific outcomes for supplemental screening methods, such as magnetic resonance imaging ... molecular breast imaging, or ultrasonography is necessary to understand which screening method beyond DBT is best for average-risk women with heterogeneous or extremely dense breasts,” the editorialists wrote.

This research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. Dr. Lowry reported grants from GE Healthcare outside the submitted work. The editorialists didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.

In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the baseline exam, according to a review of nearly 1.6 million screenings.

At baseline, DBT improved recall and cancer detection rates for all women. On subsequent exams, differences in screening performance between DBT and DM varied by age and density subgroups. However, there were no significant differences in recall or cancer detection rates among women with extremely dense breasts in any age group.

Kathryn Lowry, MD, of the University of Washington in Seattle, and colleagues reported these findings in JAMA Network Open.

“Our findings suggest that density likely should not be used as a criterion to triage use of DBT for routine screening in settings where DBT is not universally available, as has been reported in physician surveys,” the authors wrote. “The largest absolute improvements of DBT screening were achieved on the baseline screening examination, suggesting that women presenting for their first screening examination are particularly important to prioritize for DBT,” regardless of breast density or age.
 

Study details

Dr. Lowry and colleagues reviewed 1,584,079 screenings in women aged 40-79 years. The exams were done from January 2010 to April 2018 at Breast Cancer Surveillance Consortium facilities across the United States.

Sixty-five percent of the exams were in White, non-Hispanic women, 25.2% were in women younger than 50 years, and 42.4% were in women with heterogeneously dense or extremely dense breasts. Subjects had no history of breast cancer, mastectomy, or breast augmentation.

The investigators compared the performance of 1,273,492 DMs with 310,587 DBTs across the four Breast Imaging Reporting and Database System density types: almost entirely fatty, scattered fibroglandular density, heterogeneously dense, and extremely dense.

Findings were adjusted for race, family breast cancer history, and other potential confounders.
 

Recall and cancer detection rates

At baseline, recall and cancer detection rates were better with DBT than with DM, regardless of breast density subtype or patient age.

For instance, in women aged 50-59 years, screening recalls per 1,000 exams dropped from 241 with DM to 204 with DBT (relative risk, 0.84; 95% confidence interval, 0.73-0.98). Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT (RR, 1.50; 95% CI, 1.10-2.08).

On follow-up exams, recall rates were lower with DBT for women with scattered fibroglandular density and heterogeneously dense breasts in all age groups, as well as in women with almost entirely fatty breasts aged 50-79 years.

“By contrast, there were no significant differences in recall rates in women with extremely dense breasts in any age group,” the authors wrote.

Cancer detection rates on follow-up exams varied by age and breast density.

Cancer detection rates were higher with DBT than with DM in women with heterogeneously dense breasts in all age groups and in women with scattered fibroglandular density at 50-59 years of age and 60-79 years of age. However, cancer detection rates were not significantly different with DBT or DM for women with almost entirely fatty breasts or extremely dense breasts of any age.
 

Implications and next steps

Dr. Lowry and colleagues noted that use of DBT has increased steadily since it was approved by the Food and Drug Administration in 2011, driven by studies demonstrating, among other things, earlier detection of invasive cancers.

The problem has been that previous investigations “largely dichotomized dense (heterogeneously dense and extremely dense) and nondense (almost entirely fat and scattered fibroglandular densities) categories,” the authors wrote. Therefore, the nuance of benefit across density subtypes hasn’t been clear.

The finding that “screening benefits of DBT differ for women with heterogeneously dense breasts [versus] extremely dense breasts is especially important in the current landscape of density legislation and demand for supplemental screening tests beyond mammography. To date, most state mandates and ... proposed federal legislation have uniformly grouped women with heterogeneously dense breasts and those with extremely dense breasts as a single population,” the authors wrote.

As the new findings suggest, “there are important differences in performance that may not be appreciated by combining density categories,” the authors added.

The results “suggest that women with extremely dense breast tissue may benefit more from additional screening than women with heterogeneously dense breasts who undergo tomosynthesis mammography,” Catherine Tuite, MD, of Fox Chase Cancer Center in Philadelphia, and colleagues wrote in a related editorial.

“Research to determine density and risk-specific outcomes for supplemental screening methods, such as magnetic resonance imaging ... molecular breast imaging, or ultrasonography is necessary to understand which screening method beyond DBT is best for average-risk women with heterogeneous or extremely dense breasts,” the editorialists wrote.

This research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. Dr. Lowry reported grants from GE Healthcare outside the submitted work. The editorialists didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.

EXPERT COMMENTARY

Although recommending screening mammograms continues to represent the standard of care, studies from the United States and abroad have questioned their value.^1-3

In the June issue of JAMA Network Open, Australian investigators assessed the relative impacts of mammography screening and adjuvant therapy on breast cancer mortality, using data from population-based studies from 1982 through 2013.⁴ In recent decades, screening has increased substantially among Australian women.

Details of the study

Burton and Stevenson identified 76,630 women included in the Victorian Cancer Registry with invasive breast cancer in the state of Victoria, where women aged 50 to 69 are offered biennial screening.⁴ During the study’s time period, the use of adjuvant tamoxifen and chemotherapy increased substantially.

In the 31-year period assessed in this study, breast cancer mortality declined considerably. During the same period, however, the incidence of advanced breast cancer doubled.

These findings from Australia parallel those from the United States, Holland, and Norway, where the incidence of advanced breast cancer was stable or increased after screening mammography was introduced.^1-3

According to Burton and Stevenson, the increased incidence of advanced cancer clarifies that screening mammography is not responsible for declining breast cancer mortality, but all of the decline in mortality can be attributed to increased uptake of adjuvant therapy.

The authors concluded that since screening mammography does not reduce breast cancer mortality, state-sponsored screens should be discontinued.

Study strengths and limitations

Relevant data for this study were obtained from large population-based surveys for premenopausal and postmenopausal women with breast cancer.

The authors noted, however, that this analysis of observational data examining time trends across the study period can show only associations among breast cancer mortality, mammography screening participation, and adjuvant therapy uptake, and that causality can only be inferred.

The study in perspective

Although some will view the findings and recommendations of these Australian authors with skepticism or even hostility, I view their findings as good news—we have improved the treatment of breast cancer so dramatically that the benefits of finding early tumors with screening mammography have become attenuated.

Although it is challenging given the time constraints of office visits, I try to engage in shared decision making with my patients regarding when to start and how often to have screening mammography. ●

EXPERT COMMENTARY

Although recommending screening mammograms continues to represent the standard of care, studies from the United States and abroad have questioned their value.^1-3

In the June issue of JAMA Network Open, Australian investigators assessed the relative impacts of mammography screening and adjuvant therapy on breast cancer mortality, using data from population-based studies from 1982 through 2013.⁴ In recent decades, screening has increased substantially among Australian women.

Details of the study

Burton and Stevenson identified 76,630 women included in the Victorian Cancer Registry with invasive breast cancer in the state of Victoria, where women aged 50 to 69 are offered biennial screening.⁴ During the study’s time period, the use of adjuvant tamoxifen and chemotherapy increased substantially.

In the 31-year period assessed in this study, breast cancer mortality declined considerably. During the same period, however, the incidence of advanced breast cancer doubled.

These findings from Australia parallel those from the United States, Holland, and Norway, where the incidence of advanced breast cancer was stable or increased after screening mammography was introduced.^1-3

According to Burton and Stevenson, the increased incidence of advanced cancer clarifies that screening mammography is not responsible for declining breast cancer mortality, but all of the decline in mortality can be attributed to increased uptake of adjuvant therapy.

The authors concluded that since screening mammography does not reduce breast cancer mortality, state-sponsored screens should be discontinued.

Study strengths and limitations

Relevant data for this study were obtained from large population-based surveys for premenopausal and postmenopausal women with breast cancer.

The authors noted, however, that this analysis of observational data examining time trends across the study period can show only associations among breast cancer mortality, mammography screening participation, and adjuvant therapy uptake, and that causality can only be inferred.

The study in perspective

Although some will view the findings and recommendations of these Australian authors with skepticism or even hostility, I view their findings as good news—we have improved the treatment of breast cancer so dramatically that the benefits of finding early tumors with screening mammography have become attenuated.

Although it is challenging given the time constraints of office visits, I try to engage in shared decision making with my patients regarding when to start and how often to have screening mammography. ●

EXPERT COMMENTARY

Although recommending screening mammograms continues to represent the standard of care, studies from the United States and abroad have questioned their value.^1-3

In the June issue of JAMA Network Open, Australian investigators assessed the relative impacts of mammography screening and adjuvant therapy on breast cancer mortality, using data from population-based studies from 1982 through 2013.⁴ In recent decades, screening has increased substantially among Australian women.

Details of the study

Burton and Stevenson identified 76,630 women included in the Victorian Cancer Registry with invasive breast cancer in the state of Victoria, where women aged 50 to 69 are offered biennial screening.⁴ During the study’s time period, the use of adjuvant tamoxifen and chemotherapy increased substantially.

In the 31-year period assessed in this study, breast cancer mortality declined considerably. During the same period, however, the incidence of advanced breast cancer doubled.

These findings from Australia parallel those from the United States, Holland, and Norway, where the incidence of advanced breast cancer was stable or increased after screening mammography was introduced.^1-3

According to Burton and Stevenson, the increased incidence of advanced cancer clarifies that screening mammography is not responsible for declining breast cancer mortality, but all of the decline in mortality can be attributed to increased uptake of adjuvant therapy.

The authors concluded that since screening mammography does not reduce breast cancer mortality, state-sponsored screens should be discontinued.

Study strengths and limitations

Relevant data for this study were obtained from large population-based surveys for premenopausal and postmenopausal women with breast cancer.

The authors noted, however, that this analysis of observational data examining time trends across the study period can show only associations among breast cancer mortality, mammography screening participation, and adjuvant therapy uptake, and that causality can only be inferred.

The study in perspective

Although some will view the findings and recommendations of these Australian authors with skepticism or even hostility, I view their findings as good news—we have improved the treatment of breast cancer so dramatically that the benefits of finding early tumors with screening mammography have become attenuated.

Although it is challenging given the time constraints of office visits, I try to engage in shared decision making with my patients regarding when to start and how often to have screening mammography. ●

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

The history of mammography provides a powerful example of the connection between social factors and the rise of a medical technology. It is also an object lesson in the profound difficulties that the medical community faces when trying to evaluate and embrace new discoveries in such a complex area as cancer diagnosis and treatment, especially when tied to issues of sex-based bias and gender identity. Given its profound ties to women’s lives and women’s bodies, mammography holds a unique place in the history of cancer. Part 1 will examine the technological imperatives driving mammography forward, and part 2 will address the social factors that promoted and inhibited the developing technology.

All that glitters

Innovations in technology have contributed so greatly to the progress of medical science in saving and improving patients’ lives that the lure of new technology and the desire to see it succeed and to embrace it has become profound.

Public domain

In a debate on the adoption of new technologies, Michael Rosen, MD, a surgeon at the Cleveland Clinic, Ohio, pointed out the inherent risks in the life cycle of medical technology: “The stages of surgical innovation have been well described as moving from the generation of a hypothesis with an early promising report to being accepted conclusively as a new standard without formal testing. As the life cycle continues and comparative effectiveness data begin to emerge slowly through appropriately designed trials, the procedure or device is often ultimately abandoned.”¹

The history of mammography bears out this grim warning in example after example as an object lesson, revealing not only the difficulties involved in the development of new medical technologies, but also the profound problems involved in validating the effectiveness and appropriateness of a new technology from its inception to the present.
 

A modern failure?

In fact, one of the more modern developments in mammography technology – digital imaging – has recently been called into question with regard to its effectiveness in saving lives, even as the technology continues to spread throughout the medical community.

A recent meta-analysis has shown that there is little or no improvement in outcomes of breast cancer screening when using digital analysis and screening mammograms vs. traditional film recording.

The meta-analysis assessed 24 studies with a combined total of 16,583,743 screening examinations (10,968,843 film and 5,614,900 digital). The study found that the difference in cancer detection rate using digital rather than film screening showed an increase of only 0.51 detections per 1,000 screens.

The researchers concluded “that while digital mammography is beneficial for medical facilities due to easier storage and handling of images, these results suggest the transition from film to digital mammography has not resulted in health benefits for screened women.”²

In fact, the researchers added that “This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.”²

None of the nine main randomized clinical trials that were used to determine the effectiveness of mammography screening from the 1960s to the 1990s used digital or 3-D digital mammography (digital breast tomosynthesis or DBT). The earliest trial used direct-exposure film mammography and the others relied upon screen-film mammography.³ And yet the assumptions of the validity of the new digital technologies were predicated on the generalized acceptance of the validity of screening derived from these studies, and a corollary assumption that any technological improvement in the quality of the image must inherently be an improvement of the overall results of screening.

The failure of new technologies to meet expectations is a sobering corrective to the high hopes of researchers, practitioners, and patient groups alike, and is perhaps destined to contribute more to the parallel history of controversy and distrust concerning the risk/benefits of mammography that has been a media and scientific mainstay.

Too often the history of medical technology has found disappointment at the end of the road for new discoveries. But although the disappointing results of digital screening might be considered a failure in the progress of mammography, it is likely just another pause on the road of this technology, the history of which has been rocky from the start.
 

The need for a new way of looking

The rationale behind the original and continuing development of mammography is a simple one, common to all cancer screening methods – the belief that the earlier the detection of a cancer, the more likely it is to be treated effectively with the therapeutic regimens at hand. While there is some controversy regarding the cost-benefit ratio of screening, especially when therapies for breast cancer are not perfect and vary widely in expense and availability globally, the driving belief has been that mammography provides an outcomes benefit in allowing early surgical and chemoradiation therapy with a curative intent.

There were two main driving forces behind the early development of mammography. The first was the highly lethal nature of breast cancer, especially when it was caught too late and had spread too far to benefit from the only available option at the time – surgery. The second was the severity of the surgical treatment, the only therapeutic option at the time, and the distressing number of women who faced the radical mastectomy procedure pioneered by physicians William Stewart Halsted (1852-1922) at Johns Hopkins University, Baltimore, and Willy Meyer (1858-1932) in New York.

In 1894, in an era when the development of anesthetics and antisepsis made ever more difficult surgical procedures possible without inevitably killing the patient, both men separately published their results of a highly extensive operation that consisted of removal of the breast, chest muscles, and axillary lymph nodes.

As long as there was no presurgical method of determining the extent of a breast cancer’s spread, much less an ability to visually distinguish malignant from benign growths, this “better safe than sorry” approach became the default approach of an increasing number of surgeons, and the drastic solution of radical mastectomy was increasingly applied universally.

But in 1895, with the discovery of x-rays, medical science recognized a nearly miraculous technology for visualizing the inside of the body, and radioactive materials were also routinely used in medical therapies, by both legitimate practitioners and hucksters.

However, in the very early days, the users of x-rays were unaware that large radiation doses could have serious biological effects and had no way of determining radiation field strength and accumulating dosage.

In fact, early calibration of x-ray tubes was based on the amount of skin reddening (erythema) produced when the operator placed a hand directly in the x-ray beam.

It was in this environment that, within only a few decades, the new x-rays, especially with the development of improvements in mammography imaging, were able in many cases to identify smaller, more curable breast cancers. This eventually allowed surgeons to develop and use less extensive operations than the highly disfiguring radical mastectomy that was simultaneously dreaded for its invasiveness and embraced for its life-saving potential.⁴
 

Pioneering era

United States. Public Health Service

The technological history of mammography was thus driven by the quest for better imaging and reproducibility in order to further the hopes of curative surgical approaches.

In 1913, the German surgeon Albert Salomon (1883-1976) was the first to detect breast cancer using x-rays, but its clinical use was not established, as the images published in his “Beiträge zur pathologie und klinik der mammakarzinome (Contributions to the pathology and clinic of breast cancers)” were photographs of postsurgical breast specimens that illustrated the anatomy and spread of breast cancer tumors but were not adapted to presurgical screening.

After Salomon’s work was published in 1913, there was no new mammography literature published until 1927, when German surgeon Otto Kleinschmidt (1880-1948) published a report describing the world’s first authentic mammography, which he attributed to his mentor, the plastic surgeon Erwin Payr (1871-1946).⁵

Public Domain

This was followed soon after in 1930 by the work of radiologist Stafford L. Warren (1896-1981), of the University of Rochester (N.Y.), who published a paper on the use of standard roentgenograms for the in vivo preoperative assessment of breast malignancies. His technique involved the use of a stereoscopic system with a grid mechanism and intensifying screens to amplify the image. Breast compression was not involved in his mammogram technique. “Dr. Warren claimed to be correct 92% of the time when using this technique to predict malignancy.”⁵

His study of 119 women with a histopathologic diagnosis (61 benign and 58 malignant) demonstrated the feasibility of the technique for routine use and “created a surge of interest.”⁶

But the technology of the time proved difficult to use, and the results difficult to reproduce from laboratory to laboratory, and ultimately did not gain wide acceptance. Among Warren’s other claims to fame, he was a participant in the Manhattan Project and was a member of the teams sent to assess radiation damage in Hiroshima and Nagasaki after the dropping of the atomic bombs.

And in fact, future developments in mammography and all other x-ray screening techniques included attempts to minimize radiation exposure; such attempts were driven, in part, by the tragic impact of atomic bomb radiation and the medical studies carried out on the survivors.
 

An image more deadly than the disease

Further improvements in mammography technique occurred through the 1930s and 1940s, including better visualization of the mammary ducts based upon the pioneering studies of Emil Ries, MD, in Chicago, who, along with Nymphus Frederick Hicken, MD (1900-1998), reported on the use of contrast mammography (also known as ductography or galactography). On a side note, Dr. Hicken was responsible for introducing the terms mammogram and mammography in 1937.

Problems with ductography, which involved the injection of a radiographically opaque contrast agent into the nipple, occurred when the early contrast agents, such as oil-based lipiodol, proved to be toxic and capable of causing abscesses.⁷This advance led to the development of other agents, and among the most popular at the time was one that would prove deadly to many.

Thorotrast, first used in 1928, was widely embraced because of its lack of immediately noticeable side effects and the high-quality contrast it provided. Thorotrast was a suspension of radioactive thorium dioxide particles, which gained popularity for use as a radiological imaging agent from the 1930s to 1950s throughout the world, being used in an estimated 2-10 million radiographic exams, primarily for neurosurgery.

In the 1920s and 1930s, world governments had begun to recognize the dangers of radiation exposure, especially among workers, but thorotrast was a unique case because, unbeknownst to most practitioners at the time, thorium dioxide was retained in the body for the lifetime of the patient, with 70% deposited in the liver, 20% in the spleen, and the remaining in the bony medulla and in the peripheral lymph nodes.

Nineteen years after the first use of thorotrast, the first case of a human malignant tumor attributed to its exposure was reported. “Besides the liver neoplasm cases, aplastic anemia, leukemia and an impressive incidence of chromosome aberrations were registered in exposed individuals.”⁸

Despite its widespread adoption elsewhere, especially in Japan, the use of thorotrast never became popular in the United States, in part because in 1932 and 1937, warnings were issued by the American Medical Association to restrict its use.⁹

There was a shift to the use of iodinated hydrophilic molecules as contrast agents for conventional x-ray, computed tomography, and fluoroscopy procedures.⁹ However, it was discovered that these agents, too, have their own risks and dangerous side effects. They can cause severe adverse effects, including allergies, cardiovascular diseases, and nephrotoxicity in some patients.
 

Slow adoption and limited results

Between 1930 and 1950, Dr. Warren, Jacob Gershon-Cohen, MD (1899-1971) of Philadelphia, and radiologist Raul Leborgne of Uruguay “spread the gospel of mammography as an adjunct to physical examination for the diagnosis of breast cancer.”⁴ The latter also developed the breast compression technique to produce better quality images and lower the radiation exposure needed, and described the differences that could be visualized between benign and malign microcalcifications.

But despite the introduction of improvements such as double-emulsion film and breast compression to produce higher-quality images, “mammographic films often remained dark and hazy. Moreover, the new techniques, while improving the images, were not easily reproduced by other investigators and clinicians,” and therefore were still not widely adopted.⁴

Little noticeable effect of mammography

Although the technology existed and had its popularizers, mammography had little impact on an epidemiological level.

There was no major change in the mean maximum breast cancer tumor diameter and node positivity rate detected over the 20 years from 1929 to 1948.10 However, starting in the late 1940s, the American Cancer Society began public education campaigns and early detection education, and thereafter, there was a 3% decline in mean maximum diameter of tumor size seen every 10 years until 1968.

“We have interpreted this as the effect of public education and professional education about early detection through television, print media, and professional publications that began in 1947 because no other event was known to occur that would affect cancer detection beginning in the late 1940s.”¹⁰

However, the early detection methods at the time were self-examination and clinical examination for lumps, with mammography remaining a relatively limited tool until its general acceptance broadened a few decades later.
 

Robert Egan, “Father of Mammography,” et al.

United States. Public Health Service

The broad acceptance of mammography as a screening tool and its impacts on a broad population level resulted in large part from the work of Robert L. Egan, MD (1921-2001) in the late 1950s and 1960s.

Dr. Egan’s work was inspired in 1956 by a presentation by a visiting fellow, Jean Pierre Batiani, who brought a mammogram clearly showing a breast cancer from his institution, the Curie Foundation in Paris. The image had been made using very low kilowattage, high tube currents, and fine-grain film.

Dr. Egan, then a resident in radiology, was given the task by the head of his department of reproducing the results.

In 1959, Dr. Egan, then at the University of Texas MD Anderson Cancer Center, Houston, published a combined technique that used a high-milliamperage–low-voltage technique, a fine-grain intensifying screen, and single-emulsion films for mammography, thereby decreasing the radiation exposure significantly from previous x-ray techniques and improving the visualization and reproducibility of screening.

By 1960, Dr. Egan reported on 1,000 mammography cases at MD Anderson, demonstrating the ability of proper screening to detect unsuspected cancers and to limit mastectomies on benign masses. Of 245 breast cancers ultimately confirmed by biopsy, 238 were discovered by mammography, 19 of which were in women whose physical examinations had revealed no breast pathology. One of the cancers was only 8 mm in diameter when sectioned at biopsy.

Dr. Egan’s findings prompted an investigation by the Cancer Control Program (CCP) of the U.S. Public Health Service and led to a study jointly conducted by the National Cancer Institute and MD Anderson Hospital and the CCP, which involved 24 institutions and 1,500 patients.

“The results showed a 21% false-negative rate and a 79% true-positive rate for screening studies using Egan’s technique. This was a milestone for women’s imaging in the United States. Screening mammography was off to a tentative start.”⁵

“Egan was the man who developed a smooth-riding automobile compared to a Model T. He put mammography on the map and made it an intelligible, reproducible study. In short, he was the father of modern mammography,” according to his professor, mentor, and fellow mammography pioneer Gerald Dodd, MD (Emory School of Medicine website biography).

In 1964 Dr. Egan published his definitive book, “Mammography,” and in 1965 he hosted a 30-minute audiovisual presentation describing in detail his technique.¹¹

The use of mammography was further powered by improved methods of preoperative needle localization, pioneered by Richard H. Gold, MD, in 1963 at Jefferson Medical College, Philadelphia, which eased obtaining a tissue diagnosis for any suspicious lesions detected in the mammogram. Dr. Gold performed needle localization of nonpalpable, mammographically visible lesions before biopsy, which allowed surgical resection of a smaller volume of breast tissue than was possible before.

Throughout the era, there were also incremental improvements in mammography machines and an increase in the number of commercial manufacturers.

Xeroradiography, an imaging technique adapted from xerographic photocopying, was seen as a major improvement over direct film imaging, and the technology became popular throughout the 1970s based on the research of John N. Wolfe, MD (1923-1993), who worked closely with the Xerox Corporation to improve the breast imaging process.⁶ However, this technology had all the same problems associated with running an office copying machine, including paper jams and toner issues, and the worst aspect was the high dose of radiation required. For this reason, it would quickly be superseded by the use of screen-film mammography, which eventually completely replaced the use of both xeromammography and direct-exposure film mammography.
 

The march of mammography

National Cancer Insitute/Bill Branson

A series of nine randomized clinical trials (RCTs) between the 1960s and 1990s formed the foundation of the clinical use of mammography. These studies enrolled more than 600,000 women in the United States, Canada, the United Kingdom, and Sweden. The nine main RCTs of breast cancer screening were the Health Insurance Plan of Greater New York (HIP) trial, the Edinburgh trial, the Canadian National Breast Screening Study, the Canadian National Breast Screening Study 2, the United Kingdom Age trial, the Stockholm trial, the Malmö Mammographic Screening Trial, the Gothenburg trial, and the Swedish Two-County Study.³

These trials incorporated improvements in the technology as it developed, as seen in the fact that the earliest, the HIP trial, used direct-exposure film mammography and the other trials used screen-film mammography.3

Meta-analyses of the major nine screening trials indicated that reduced breast cancer mortality with screening was dependent on age. In particular, the results for women aged 40-49 years and 50-59 years showed only borderline statistical significance, and they varied depending on how cases were accrued in individual trials. “Assuming that differences actually exist, the absolute breast cancer mortality reduction per 10,000 women screened for 10 years ranged from 3 for age 39-49 years; 5-8 for age 50-59 years; and 12-21 for age 60-69 years.”3 In addition the estimates for women aged 70-74 years were limited by low numbers of events in trials that had smaller numbers of women in this age group.

However, at the time, the studies had a profound influence on increasing the popularity and spread of mammography.

As mammographies became more common, standardization became an important issue and a Mammography Accreditation Program began in 1987. Originally a voluntary program, it became mandatory with the Mammography Quality Standards Act of 1992, which required all U.S. mammography facilities to become accredited and certified.

In 1986, the American College of Radiology proposed its Breast Imaging Reporting and Data System (BI-RADS) initiative to enable standardized reporting of mammography; the first report was released in 1993.

BI-RADS is now on its fifth edition and has addressed the use of mammography, breast ultrasonography, and breast magnetic resonance imaging, developing standardized auditing approaches for all three techniques of breast cancer imaging.6
 

The digital era and beyond

With the dawn of the 21st century, the era of digital breast cancer screening began.

The screen-film mammography (SFM) technique employed throughout the 1980s and 1990s had significant advantages over earlier x-ray films for producing more vivid images of dense breast tissues. The next technology, digital mammography, was introduced in the late 20th century, and the first system was approved by the U.S. FDA in 2000.

One of the key benefits touted for digital mammograms is the fact that the radiologist can manipulate the contrast of the images, which allows for masses to be identified that might otherwise not be visible on standard film.

However, the recent meta-analysis discussed in the introduction calls such benefits into question, and a new controversy is likely to ensue on the question of the effectiveness of digital mammography on overall clinical outcomes.

But the technology continues to evolve.

“There has been a continuous and substantial technical development from SFM to full-field digital mammography and very recently also the introduction of digital breast tomosynthesis (DBT). This technical evolution calls for new evidence regarding the performance of screening using new mammography technologies, and the evidence needed to translate new technologies into screening practice,” according to an updated assessment by the U.S. Preventive Services Task Force.¹²

DBT was approved by the Food and Drug Administration in 2011. The technology involves the creation of a series of images, which are assembled into a 3-D–like image of breast slices. Traditional digital mammography creates a 2-D image of a flattened breast, and the radiologist must peer through the layers to find abnormalities. DBT uses a computer algorithm to reconstruct multiple low-dose digital images of the breast that can be displayed individually or in cinematic mode.¹³

Early trials showed a significant benefit of DBT in detecting new and smaller breast cancers, compared with standard digital mammography.

In women in their 40s, DBT found 1.7 more cancers than digital mammography for every 1,000 exams of women with normal breast tissue. In addition, 16.3% of women in this age group who were screened using digital mammography received callbacks, versus 11.7% of those screened using DBT. For younger women with dense breasts, the advantage of DBT was even greater, with 2.27 more cancers found for every 1,000 women screened. Whether such results will lead to clinically improved outcomes remains a question. “It can still miss cancers. Also, like traditional mammography, DBT might not reduce deaths from tumors that are very aggressive and fast-growing. And some women will still be called back unnecessarily for false-positive results.”¹⁴

But such technological advances further the hopes of researchers and patients alike.
 

Conclusion

Medical technology is driven both by advances in science and by the demands of patients and physicians for improved outcomes. The history of mammography, for example, is tied to the scientific advancements in x-ray technology, which allowed physicians for the first time to peer inside a living body without a scalpel at hand. But mammography was also an outgrowth of the profound need of the surgeon to identify cancerous masses in the breast at an early-enough stage to attempt a cure, while simultaneously minimizing the radical nature of the surgery required.

And while seeing is believing, the need to see and verify what was seen in order to make life-and-death decisions drove the demand for improvements in the technology of mammography throughout most of the 20th century and beyond.

The tortuous path from the early and continuing snafus with contrast agents to the apparent failure of the promise of digital technology serves as a continuing reminder of the hopes and perils that developing medical technologies present. It will be interesting to see if further refinements to mammography, such as DBT, will enhance the technology enough to have a major impact on countless women’s lives, or if new developments in magnetic resonance imaging and ultrasound make traditional mammography a relic of the past.

Part 2 of this history will present the social dynamics intimately involved with the rise and promulgation of mammography and how social need and public fears and controversies affected its development and spread as much, if not more, than technological innovation.

This article could only touch upon the myriad of details and technologies involved in the history of mammography, and I urge interested readers to check out the relevant references for far more in-depth and fascinating stories from its complex and controversial past.

mlesney@mdedge.com

References

1. Felix EL, Rosen M, Earle D. “Curbing Our Enthusiasm for Surgical Innovation: Is It a Good Thing or Bad Thing?” The Great Debates, General Surgery News, 2018 Oct 17

2. J Natl Cancer Inst. 2020 Jun 23. doi: 10.1093/jnci/djaa080.

3. Nelson H et al. Screening for Breast Cancer: A Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation. Evidence Synthesis No. 124. (Rockville, Md.: U.S. Agency for Healthcare Research and Quality, 2016 Jan, pp. 29-49)4. Lerner, BH. “To See Today With the Eyes of Tomorrow: A History of Screening Mammography,” background paper for Patlak M et al., Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer (Washington: National Academies Press, 2001).

5. Grady I, Hansen P. Chapter 28: Mammography in “Kuerer’s Breast Surgical Oncology”(New York: McGaw-Hill Medical, 2010)

6. Radiology. 2014 Nov;273(2 Suppl):S23-44.

7. Bassett LW, Kim CH. (2003) Chapter 1: Ductography in Dershaw DD (eds) “Imaging-Guided Interventional Breast Techniques” (New York: Springer, 2003, pp. 1-30).

8. Cuperschmid EM, Ribeiro de Campos TP. 2009 International Nuclear Atlantic Conference, Rio de Janeiro, Sept 27–Oct 2, 2009

9. Bioscience Microflora. 2000;19(2):107-16.

10. Cady B. New era in breast cancer. Impact of screening on disease presentation. Surg Oncol Clin N Am. 1997 Apr;6(2):195-202.

11. Egan R. “Mammography Technique.” Audiovisual presentation. (Washington: U.S. Public Health Service, 1965).

12. Zackrisson S, Houssami N. Chapter 13: Evolution of Mammography Screening: From Film Screen to Digital Breast Tomosynthesis in “Breast Cancer Screening: An Examination of Scientific Evidence” (Cambridge, Mass.: Academic Press, 2016, pp. 323-46).13. Melnikow J et al. Screening for breast cancer with digital breast tomosynthesis. Evidence Synthesis No. 125 (Rockville, Md.: U.S. Agency for Healthcare Research and Quality, 2016 Jan).

14. Newer breast screening technology may spot more cancers. Harvard Women’s Health Watch online, June 2019.

Mark Lesney is the editor of Hematology News and the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has worked as a writer/editor for the American Chemical Society, and has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.

The history of mammography provides a powerful example of the connection between social factors and the rise of a medical technology. It is also an object lesson in the profound difficulties that the medical community faces when trying to evaluate and embrace new discoveries in such a complex area as cancer diagnosis and treatment, especially when tied to issues of sex-based bias and gender identity. Given its profound ties to women’s lives and women’s bodies, mammography holds a unique place in the history of cancer. Part 1 will examine the technological imperatives driving mammography forward, and part 2 will address the social factors that promoted and inhibited the developing technology.

All that glitters

Innovations in technology have contributed so greatly to the progress of medical science in saving and improving patients’ lives that the lure of new technology and the desire to see it succeed and to embrace it has become profound.

Public domain

In a debate on the adoption of new technologies, Michael Rosen, MD, a surgeon at the Cleveland Clinic, Ohio, pointed out the inherent risks in the life cycle of medical technology: “The stages of surgical innovation have been well described as moving from the generation of a hypothesis with an early promising report to being accepted conclusively as a new standard without formal testing. As the life cycle continues and comparative effectiveness data begin to emerge slowly through appropriately designed trials, the procedure or device is often ultimately abandoned.”¹

The history of mammography bears out this grim warning in example after example as an object lesson, revealing not only the difficulties involved in the development of new medical technologies, but also the profound problems involved in validating the effectiveness and appropriateness of a new technology from its inception to the present.
 

A modern failure?

In fact, one of the more modern developments in mammography technology – digital imaging – has recently been called into question with regard to its effectiveness in saving lives, even as the technology continues to spread throughout the medical community.

A recent meta-analysis has shown that there is little or no improvement in outcomes of breast cancer screening when using digital analysis and screening mammograms vs. traditional film recording.

The meta-analysis assessed 24 studies with a combined total of 16,583,743 screening examinations (10,968,843 film and 5,614,900 digital). The study found that the difference in cancer detection rate using digital rather than film screening showed an increase of only 0.51 detections per 1,000 screens.

The researchers concluded “that while digital mammography is beneficial for medical facilities due to easier storage and handling of images, these results suggest the transition from film to digital mammography has not resulted in health benefits for screened women.”²

In fact, the researchers added that “This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.”²

None of the nine main randomized clinical trials that were used to determine the effectiveness of mammography screening from the 1960s to the 1990s used digital or 3-D digital mammography (digital breast tomosynthesis or DBT). The earliest trial used direct-exposure film mammography and the others relied upon screen-film mammography.³ And yet the assumptions of the validity of the new digital technologies were predicated on the generalized acceptance of the validity of screening derived from these studies, and a corollary assumption that any technological improvement in the quality of the image must inherently be an improvement of the overall results of screening.

The failure of new technologies to meet expectations is a sobering corrective to the high hopes of researchers, practitioners, and patient groups alike, and is perhaps destined to contribute more to the parallel history of controversy and distrust concerning the risk/benefits of mammography that has been a media and scientific mainstay.

Too often the history of medical technology has found disappointment at the end of the road for new discoveries. But although the disappointing results of digital screening might be considered a failure in the progress of mammography, it is likely just another pause on the road of this technology, the history of which has been rocky from the start.
 

The need for a new way of looking

The rationale behind the original and continuing development of mammography is a simple one, common to all cancer screening methods – the belief that the earlier the detection of a cancer, the more likely it is to be treated effectively with the therapeutic regimens at hand. While there is some controversy regarding the cost-benefit ratio of screening, especially when therapies for breast cancer are not perfect and vary widely in expense and availability globally, the driving belief has been that mammography provides an outcomes benefit in allowing early surgical and chemoradiation therapy with a curative intent.

There were two main driving forces behind the early development of mammography. The first was the highly lethal nature of breast cancer, especially when it was caught too late and had spread too far to benefit from the only available option at the time – surgery. The second was the severity of the surgical treatment, the only therapeutic option at the time, and the distressing number of women who faced the radical mastectomy procedure pioneered by physicians William Stewart Halsted (1852-1922) at Johns Hopkins University, Baltimore, and Willy Meyer (1858-1932) in New York.

In 1894, in an era when the development of anesthetics and antisepsis made ever more difficult surgical procedures possible without inevitably killing the patient, both men separately published their results of a highly extensive operation that consisted of removal of the breast, chest muscles, and axillary lymph nodes.

As long as there was no presurgical method of determining the extent of a breast cancer’s spread, much less an ability to visually distinguish malignant from benign growths, this “better safe than sorry” approach became the default approach of an increasing number of surgeons, and the drastic solution of radical mastectomy was increasingly applied universally.

But in 1895, with the discovery of x-rays, medical science recognized a nearly miraculous technology for visualizing the inside of the body, and radioactive materials were also routinely used in medical therapies, by both legitimate practitioners and hucksters.

However, in the very early days, the users of x-rays were unaware that large radiation doses could have serious biological effects and had no way of determining radiation field strength and accumulating dosage.

In fact, early calibration of x-ray tubes was based on the amount of skin reddening (erythema) produced when the operator placed a hand directly in the x-ray beam.

It was in this environment that, within only a few decades, the new x-rays, especially with the development of improvements in mammography imaging, were able in many cases to identify smaller, more curable breast cancers. This eventually allowed surgeons to develop and use less extensive operations than the highly disfiguring radical mastectomy that was simultaneously dreaded for its invasiveness and embraced for its life-saving potential.⁴
 

Pioneering era

United States. Public Health Service

The technological history of mammography was thus driven by the quest for better imaging and reproducibility in order to further the hopes of curative surgical approaches.

In 1913, the German surgeon Albert Salomon (1883-1976) was the first to detect breast cancer using x-rays, but its clinical use was not established, as the images published in his “Beiträge zur pathologie und klinik der mammakarzinome (Contributions to the pathology and clinic of breast cancers)” were photographs of postsurgical breast specimens that illustrated the anatomy and spread of breast cancer tumors but were not adapted to presurgical screening.

After Salomon’s work was published in 1913, there was no new mammography literature published until 1927, when German surgeon Otto Kleinschmidt (1880-1948) published a report describing the world’s first authentic mammography, which he attributed to his mentor, the plastic surgeon Erwin Payr (1871-1946).⁵

Public Domain

This was followed soon after in 1930 by the work of radiologist Stafford L. Warren (1896-1981), of the University of Rochester (N.Y.), who published a paper on the use of standard roentgenograms for the in vivo preoperative assessment of breast malignancies. His technique involved the use of a stereoscopic system with a grid mechanism and intensifying screens to amplify the image. Breast compression was not involved in his mammogram technique. “Dr. Warren claimed to be correct 92% of the time when using this technique to predict malignancy.”⁵

His study of 119 women with a histopathologic diagnosis (61 benign and 58 malignant) demonstrated the feasibility of the technique for routine use and “created a surge of interest.”⁶

But the technology of the time proved difficult to use, and the results difficult to reproduce from laboratory to laboratory, and ultimately did not gain wide acceptance. Among Warren’s other claims to fame, he was a participant in the Manhattan Project and was a member of the teams sent to assess radiation damage in Hiroshima and Nagasaki after the dropping of the atomic bombs.

And in fact, future developments in mammography and all other x-ray screening techniques included attempts to minimize radiation exposure; such attempts were driven, in part, by the tragic impact of atomic bomb radiation and the medical studies carried out on the survivors.
 

An image more deadly than the disease

Further improvements in mammography technique occurred through the 1930s and 1940s, including better visualization of the mammary ducts based upon the pioneering studies of Emil Ries, MD, in Chicago, who, along with Nymphus Frederick Hicken, MD (1900-1998), reported on the use of contrast mammography (also known as ductography or galactography). On a side note, Dr. Hicken was responsible for introducing the terms mammogram and mammography in 1937.

Problems with ductography, which involved the injection of a radiographically opaque contrast agent into the nipple, occurred when the early contrast agents, such as oil-based lipiodol, proved to be toxic and capable of causing abscesses.⁷This advance led to the development of other agents, and among the most popular at the time was one that would prove deadly to many.

Thorotrast, first used in 1928, was widely embraced because of its lack of immediately noticeable side effects and the high-quality contrast it provided. Thorotrast was a suspension of radioactive thorium dioxide particles, which gained popularity for use as a radiological imaging agent from the 1930s to 1950s throughout the world, being used in an estimated 2-10 million radiographic exams, primarily for neurosurgery.

In the 1920s and 1930s, world governments had begun to recognize the dangers of radiation exposure, especially among workers, but thorotrast was a unique case because, unbeknownst to most practitioners at the time, thorium dioxide was retained in the body for the lifetime of the patient, with 70% deposited in the liver, 20% in the spleen, and the remaining in the bony medulla and in the peripheral lymph nodes.

Nineteen years after the first use of thorotrast, the first case of a human malignant tumor attributed to its exposure was reported. “Besides the liver neoplasm cases, aplastic anemia, leukemia and an impressive incidence of chromosome aberrations were registered in exposed individuals.”⁸

Despite its widespread adoption elsewhere, especially in Japan, the use of thorotrast never became popular in the United States, in part because in 1932 and 1937, warnings were issued by the American Medical Association to restrict its use.⁹

There was a shift to the use of iodinated hydrophilic molecules as contrast agents for conventional x-ray, computed tomography, and fluoroscopy procedures.⁹ However, it was discovered that these agents, too, have their own risks and dangerous side effects. They can cause severe adverse effects, including allergies, cardiovascular diseases, and nephrotoxicity in some patients.
 

Slow adoption and limited results

Between 1930 and 1950, Dr. Warren, Jacob Gershon-Cohen, MD (1899-1971) of Philadelphia, and radiologist Raul Leborgne of Uruguay “spread the gospel of mammography as an adjunct to physical examination for the diagnosis of breast cancer.”⁴ The latter also developed the breast compression technique to produce better quality images and lower the radiation exposure needed, and described the differences that could be visualized between benign and malign microcalcifications.

But despite the introduction of improvements such as double-emulsion film and breast compression to produce higher-quality images, “mammographic films often remained dark and hazy. Moreover, the new techniques, while improving the images, were not easily reproduced by other investigators and clinicians,” and therefore were still not widely adopted.⁴

Little noticeable effect of mammography

Although the technology existed and had its popularizers, mammography had little impact on an epidemiological level.

There was no major change in the mean maximum breast cancer tumor diameter and node positivity rate detected over the 20 years from 1929 to 1948.10 However, starting in the late 1940s, the American Cancer Society began public education campaigns and early detection education, and thereafter, there was a 3% decline in mean maximum diameter of tumor size seen every 10 years until 1968.

“We have interpreted this as the effect of public education and professional education about early detection through television, print media, and professional publications that began in 1947 because no other event was known to occur that would affect cancer detection beginning in the late 1940s.”¹⁰

However, the early detection methods at the time were self-examination and clinical examination for lumps, with mammography remaining a relatively limited tool until its general acceptance broadened a few decades later.
 

Robert Egan, “Father of Mammography,” et al.

United States. Public Health Service

The broad acceptance of mammography as a screening tool and its impacts on a broad population level resulted in large part from the work of Robert L. Egan, MD (1921-2001) in the late 1950s and 1960s.

Dr. Egan’s work was inspired in 1956 by a presentation by a visiting fellow, Jean Pierre Batiani, who brought a mammogram clearly showing a breast cancer from his institution, the Curie Foundation in Paris. The image had been made using very low kilowattage, high tube currents, and fine-grain film.

Dr. Egan, then a resident in radiology, was given the task by the head of his department of reproducing the results.

In 1959, Dr. Egan, then at the University of Texas MD Anderson Cancer Center, Houston, published a combined technique that used a high-milliamperage–low-voltage technique, a fine-grain intensifying screen, and single-emulsion films for mammography, thereby decreasing the radiation exposure significantly from previous x-ray techniques and improving the visualization and reproducibility of screening.

By 1960, Dr. Egan reported on 1,000 mammography cases at MD Anderson, demonstrating the ability of proper screening to detect unsuspected cancers and to limit mastectomies on benign masses. Of 245 breast cancers ultimately confirmed by biopsy, 238 were discovered by mammography, 19 of which were in women whose physical examinations had revealed no breast pathology. One of the cancers was only 8 mm in diameter when sectioned at biopsy.

Dr. Egan’s findings prompted an investigation by the Cancer Control Program (CCP) of the U.S. Public Health Service and led to a study jointly conducted by the National Cancer Institute and MD Anderson Hospital and the CCP, which involved 24 institutions and 1,500 patients.

“The results showed a 21% false-negative rate and a 79% true-positive rate for screening studies using Egan’s technique. This was a milestone for women’s imaging in the United States. Screening mammography was off to a tentative start.”⁵

“Egan was the man who developed a smooth-riding automobile compared to a Model T. He put mammography on the map and made it an intelligible, reproducible study. In short, he was the father of modern mammography,” according to his professor, mentor, and fellow mammography pioneer Gerald Dodd, MD (Emory School of Medicine website biography).

In 1964 Dr. Egan published his definitive book, “Mammography,” and in 1965 he hosted a 30-minute audiovisual presentation describing in detail his technique.¹¹

The use of mammography was further powered by improved methods of preoperative needle localization, pioneered by Richard H. Gold, MD, in 1963 at Jefferson Medical College, Philadelphia, which eased obtaining a tissue diagnosis for any suspicious lesions detected in the mammogram. Dr. Gold performed needle localization of nonpalpable, mammographically visible lesions before biopsy, which allowed surgical resection of a smaller volume of breast tissue than was possible before.

Throughout the era, there were also incremental improvements in mammography machines and an increase in the number of commercial manufacturers.

Xeroradiography, an imaging technique adapted from xerographic photocopying, was seen as a major improvement over direct film imaging, and the technology became popular throughout the 1970s based on the research of John N. Wolfe, MD (1923-1993), who worked closely with the Xerox Corporation to improve the breast imaging process.⁶ However, this technology had all the same problems associated with running an office copying machine, including paper jams and toner issues, and the worst aspect was the high dose of radiation required. For this reason, it would quickly be superseded by the use of screen-film mammography, which eventually completely replaced the use of both xeromammography and direct-exposure film mammography.
 

The march of mammography

National Cancer Insitute/Bill Branson

A series of nine randomized clinical trials (RCTs) between the 1960s and 1990s formed the foundation of the clinical use of mammography. These studies enrolled more than 600,000 women in the United States, Canada, the United Kingdom, and Sweden. The nine main RCTs of breast cancer screening were the Health Insurance Plan of Greater New York (HIP) trial, the Edinburgh trial, the Canadian National Breast Screening Study, the Canadian National Breast Screening Study 2, the United Kingdom Age trial, the Stockholm trial, the Malmö Mammographic Screening Trial, the Gothenburg trial, and the Swedish Two-County Study.³

These trials incorporated improvements in the technology as it developed, as seen in the fact that the earliest, the HIP trial, used direct-exposure film mammography and the other trials used screen-film mammography.3

Meta-analyses of the major nine screening trials indicated that reduced breast cancer mortality with screening was dependent on age. In particular, the results for women aged 40-49 years and 50-59 years showed only borderline statistical significance, and they varied depending on how cases were accrued in individual trials. “Assuming that differences actually exist, the absolute breast cancer mortality reduction per 10,000 women screened for 10 years ranged from 3 for age 39-49 years; 5-8 for age 50-59 years; and 12-21 for age 60-69 years.”3 In addition the estimates for women aged 70-74 years were limited by low numbers of events in trials that had smaller numbers of women in this age group.

However, at the time, the studies had a profound influence on increasing the popularity and spread of mammography.

As mammographies became more common, standardization became an important issue and a Mammography Accreditation Program began in 1987. Originally a voluntary program, it became mandatory with the Mammography Quality Standards Act of 1992, which required all U.S. mammography facilities to become accredited and certified.

In 1986, the American College of Radiology proposed its Breast Imaging Reporting and Data System (BI-RADS) initiative to enable standardized reporting of mammography; the first report was released in 1993.

BI-RADS is now on its fifth edition and has addressed the use of mammography, breast ultrasonography, and breast magnetic resonance imaging, developing standardized auditing approaches for all three techniques of breast cancer imaging.6
 

The digital era and beyond

With the dawn of the 21st century, the era of digital breast cancer screening began.

The screen-film mammography (SFM) technique employed throughout the 1980s and 1990s had significant advantages over earlier x-ray films for producing more vivid images of dense breast tissues. The next technology, digital mammography, was introduced in the late 20th century, and the first system was approved by the U.S. FDA in 2000.

One of the key benefits touted for digital mammograms is the fact that the radiologist can manipulate the contrast of the images, which allows for masses to be identified that might otherwise not be visible on standard film.

However, the recent meta-analysis discussed in the introduction calls such benefits into question, and a new controversy is likely to ensue on the question of the effectiveness of digital mammography on overall clinical outcomes.

But the technology continues to evolve.

“There has been a continuous and substantial technical development from SFM to full-field digital mammography and very recently also the introduction of digital breast tomosynthesis (DBT). This technical evolution calls for new evidence regarding the performance of screening using new mammography technologies, and the evidence needed to translate new technologies into screening practice,” according to an updated assessment by the U.S. Preventive Services Task Force.¹²

DBT was approved by the Food and Drug Administration in 2011. The technology involves the creation of a series of images, which are assembled into a 3-D–like image of breast slices. Traditional digital mammography creates a 2-D image of a flattened breast, and the radiologist must peer through the layers to find abnormalities. DBT uses a computer algorithm to reconstruct multiple low-dose digital images of the breast that can be displayed individually or in cinematic mode.¹³

Early trials showed a significant benefit of DBT in detecting new and smaller breast cancers, compared with standard digital mammography.

In women in their 40s, DBT found 1.7 more cancers than digital mammography for every 1,000 exams of women with normal breast tissue. In addition, 16.3% of women in this age group who were screened using digital mammography received callbacks, versus 11.7% of those screened using DBT. For younger women with dense breasts, the advantage of DBT was even greater, with 2.27 more cancers found for every 1,000 women screened. Whether such results will lead to clinically improved outcomes remains a question. “It can still miss cancers. Also, like traditional mammography, DBT might not reduce deaths from tumors that are very aggressive and fast-growing. And some women will still be called back unnecessarily for false-positive results.”¹⁴

But such technological advances further the hopes of researchers and patients alike.
 

Conclusion

Medical technology is driven both by advances in science and by the demands of patients and physicians for improved outcomes. The history of mammography, for example, is tied to the scientific advancements in x-ray technology, which allowed physicians for the first time to peer inside a living body without a scalpel at hand. But mammography was also an outgrowth of the profound need of the surgeon to identify cancerous masses in the breast at an early-enough stage to attempt a cure, while simultaneously minimizing the radical nature of the surgery required.

And while seeing is believing, the need to see and verify what was seen in order to make life-and-death decisions drove the demand for improvements in the technology of mammography throughout most of the 20th century and beyond.

The tortuous path from the early and continuing snafus with contrast agents to the apparent failure of the promise of digital technology serves as a continuing reminder of the hopes and perils that developing medical technologies present. It will be interesting to see if further refinements to mammography, such as DBT, will enhance the technology enough to have a major impact on countless women’s lives, or if new developments in magnetic resonance imaging and ultrasound make traditional mammography a relic of the past.

Part 2 of this history will present the social dynamics intimately involved with the rise and promulgation of mammography and how social need and public fears and controversies affected its development and spread as much, if not more, than technological innovation.

This article could only touch upon the myriad of details and technologies involved in the history of mammography, and I urge interested readers to check out the relevant references for far more in-depth and fascinating stories from its complex and controversial past.

mlesney@mdedge.com

References

1. Felix EL, Rosen M, Earle D. “Curbing Our Enthusiasm for Surgical Innovation: Is It a Good Thing or Bad Thing?” The Great Debates, General Surgery News, 2018 Oct 17

2. J Natl Cancer Inst. 2020 Jun 23. doi: 10.1093/jnci/djaa080.

3. Nelson H et al. Screening for Breast Cancer: A Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation. Evidence Synthesis No. 124. (Rockville, Md.: U.S. Agency for Healthcare Research and Quality, 2016 Jan, pp. 29-49)4. Lerner, BH. “To See Today With the Eyes of Tomorrow: A History of Screening Mammography,” background paper for Patlak M et al., Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer (Washington: National Academies Press, 2001).

5. Grady I, Hansen P. Chapter 28: Mammography in “Kuerer’s Breast Surgical Oncology”(New York: McGaw-Hill Medical, 2010)

6. Radiology. 2014 Nov;273(2 Suppl):S23-44.

7. Bassett LW, Kim CH. (2003) Chapter 1: Ductography in Dershaw DD (eds) “Imaging-Guided Interventional Breast Techniques” (New York: Springer, 2003, pp. 1-30).

8. Cuperschmid EM, Ribeiro de Campos TP. 2009 International Nuclear Atlantic Conference, Rio de Janeiro, Sept 27–Oct 2, 2009

9. Bioscience Microflora. 2000;19(2):107-16.

10. Cady B. New era in breast cancer. Impact of screening on disease presentation. Surg Oncol Clin N Am. 1997 Apr;6(2):195-202.

11. Egan R. “Mammography Technique.” Audiovisual presentation. (Washington: U.S. Public Health Service, 1965).

12. Zackrisson S, Houssami N. Chapter 13: Evolution of Mammography Screening: From Film Screen to Digital Breast Tomosynthesis in “Breast Cancer Screening: An Examination of Scientific Evidence” (Cambridge, Mass.: Academic Press, 2016, pp. 323-46).13. Melnikow J et al. Screening for breast cancer with digital breast tomosynthesis. Evidence Synthesis No. 125 (Rockville, Md.: U.S. Agency for Healthcare Research and Quality, 2016 Jan).

14. Newer breast screening technology may spot more cancers. Harvard Women’s Health Watch online, June 2019.

Mark Lesney is the editor of Hematology News and the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has worked as a writer/editor for the American Chemical Society, and has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.

The history of mammography provides a powerful example of the connection between social factors and the rise of a medical technology. It is also an object lesson in the profound difficulties that the medical community faces when trying to evaluate and embrace new discoveries in such a complex area as cancer diagnosis and treatment, especially when tied to issues of sex-based bias and gender identity. Given its profound ties to women’s lives and women’s bodies, mammography holds a unique place in the history of cancer. Part 1 will examine the technological imperatives driving mammography forward, and part 2 will address the social factors that promoted and inhibited the developing technology.

All that glitters

Innovations in technology have contributed so greatly to the progress of medical science in saving and improving patients’ lives that the lure of new technology and the desire to see it succeed and to embrace it has become profound.

Public domain

In a debate on the adoption of new technologies, Michael Rosen, MD, a surgeon at the Cleveland Clinic, Ohio, pointed out the inherent risks in the life cycle of medical technology: “The stages of surgical innovation have been well described as moving from the generation of a hypothesis with an early promising report to being accepted conclusively as a new standard without formal testing. As the life cycle continues and comparative effectiveness data begin to emerge slowly through appropriately designed trials, the procedure or device is often ultimately abandoned.”¹

The history of mammography bears out this grim warning in example after example as an object lesson, revealing not only the difficulties involved in the development of new medical technologies, but also the profound problems involved in validating the effectiveness and appropriateness of a new technology from its inception to the present.
 

A modern failure?

In fact, one of the more modern developments in mammography technology – digital imaging – has recently been called into question with regard to its effectiveness in saving lives, even as the technology continues to spread throughout the medical community.

A recent meta-analysis has shown that there is little or no improvement in outcomes of breast cancer screening when using digital analysis and screening mammograms vs. traditional film recording.

The meta-analysis assessed 24 studies with a combined total of 16,583,743 screening examinations (10,968,843 film and 5,614,900 digital). The study found that the difference in cancer detection rate using digital rather than film screening showed an increase of only 0.51 detections per 1,000 screens.

The researchers concluded “that while digital mammography is beneficial for medical facilities due to easier storage and handling of images, these results suggest the transition from film to digital mammography has not resulted in health benefits for screened women.”²

In fact, the researchers added that “This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.”²

None of the nine main randomized clinical trials that were used to determine the effectiveness of mammography screening from the 1960s to the 1990s used digital or 3-D digital mammography (digital breast tomosynthesis or DBT). The earliest trial used direct-exposure film mammography and the others relied upon screen-film mammography.³ And yet the assumptions of the validity of the new digital technologies were predicated on the generalized acceptance of the validity of screening derived from these studies, and a corollary assumption that any technological improvement in the quality of the image must inherently be an improvement of the overall results of screening.

The failure of new technologies to meet expectations is a sobering corrective to the high hopes of researchers, practitioners, and patient groups alike, and is perhaps destined to contribute more to the parallel history of controversy and distrust concerning the risk/benefits of mammography that has been a media and scientific mainstay.

Too often the history of medical technology has found disappointment at the end of the road for new discoveries. But although the disappointing results of digital screening might be considered a failure in the progress of mammography, it is likely just another pause on the road of this technology, the history of which has been rocky from the start.
 

The need for a new way of looking

The rationale behind the original and continuing development of mammography is a simple one, common to all cancer screening methods – the belief that the earlier the detection of a cancer, the more likely it is to be treated effectively with the therapeutic regimens at hand. While there is some controversy regarding the cost-benefit ratio of screening, especially when therapies for breast cancer are not perfect and vary widely in expense and availability globally, the driving belief has been that mammography provides an outcomes benefit in allowing early surgical and chemoradiation therapy with a curative intent.

There were two main driving forces behind the early development of mammography. The first was the highly lethal nature of breast cancer, especially when it was caught too late and had spread too far to benefit from the only available option at the time – surgery. The second was the severity of the surgical treatment, the only therapeutic option at the time, and the distressing number of women who faced the radical mastectomy procedure pioneered by physicians William Stewart Halsted (1852-1922) at Johns Hopkins University, Baltimore, and Willy Meyer (1858-1932) in New York.

In 1894, in an era when the development of anesthetics and antisepsis made ever more difficult surgical procedures possible without inevitably killing the patient, both men separately published their results of a highly extensive operation that consisted of removal of the breast, chest muscles, and axillary lymph nodes.

As long as there was no presurgical method of determining the extent of a breast cancer’s spread, much less an ability to visually distinguish malignant from benign growths, this “better safe than sorry” approach became the default approach of an increasing number of surgeons, and the drastic solution of radical mastectomy was increasingly applied universally.

But in 1895, with the discovery of x-rays, medical science recognized a nearly miraculous technology for visualizing the inside of the body, and radioactive materials were also routinely used in medical therapies, by both legitimate practitioners and hucksters.

However, in the very early days, the users of x-rays were unaware that large radiation doses could have serious biological effects and had no way of determining radiation field strength and accumulating dosage.

In fact, early calibration of x-ray tubes was based on the amount of skin reddening (erythema) produced when the operator placed a hand directly in the x-ray beam.

It was in this environment that, within only a few decades, the new x-rays, especially with the development of improvements in mammography imaging, were able in many cases to identify smaller, more curable breast cancers. This eventually allowed surgeons to develop and use less extensive operations than the highly disfiguring radical mastectomy that was simultaneously dreaded for its invasiveness and embraced for its life-saving potential.⁴
 

Pioneering era

United States. Public Health Service

The technological history of mammography was thus driven by the quest for better imaging and reproducibility in order to further the hopes of curative surgical approaches.

In 1913, the German surgeon Albert Salomon (1883-1976) was the first to detect breast cancer using x-rays, but its clinical use was not established, as the images published in his “Beiträge zur pathologie und klinik der mammakarzinome (Contributions to the pathology and clinic of breast cancers)” were photographs of postsurgical breast specimens that illustrated the anatomy and spread of breast cancer tumors but were not adapted to presurgical screening.

After Salomon’s work was published in 1913, there was no new mammography literature published until 1927, when German surgeon Otto Kleinschmidt (1880-1948) published a report describing the world’s first authentic mammography, which he attributed to his mentor, the plastic surgeon Erwin Payr (1871-1946).⁵

Public Domain

This was followed soon after in 1930 by the work of radiologist Stafford L. Warren (1896-1981), of the University of Rochester (N.Y.), who published a paper on the use of standard roentgenograms for the in vivo preoperative assessment of breast malignancies. His technique involved the use of a stereoscopic system with a grid mechanism and intensifying screens to amplify the image. Breast compression was not involved in his mammogram technique. “Dr. Warren claimed to be correct 92% of the time when using this technique to predict malignancy.”⁵

His study of 119 women with a histopathologic diagnosis (61 benign and 58 malignant) demonstrated the feasibility of the technique for routine use and “created a surge of interest.”⁶

But the technology of the time proved difficult to use, and the results difficult to reproduce from laboratory to laboratory, and ultimately did not gain wide acceptance. Among Warren’s other claims to fame, he was a participant in the Manhattan Project and was a member of the teams sent to assess radiation damage in Hiroshima and Nagasaki after the dropping of the atomic bombs.

And in fact, future developments in mammography and all other x-ray screening techniques included attempts to minimize radiation exposure; such attempts were driven, in part, by the tragic impact of atomic bomb radiation and the medical studies carried out on the survivors.
 

An image more deadly than the disease

Further improvements in mammography technique occurred through the 1930s and 1940s, including better visualization of the mammary ducts based upon the pioneering studies of Emil Ries, MD, in Chicago, who, along with Nymphus Frederick Hicken, MD (1900-1998), reported on the use of contrast mammography (also known as ductography or galactography). On a side note, Dr. Hicken was responsible for introducing the terms mammogram and mammography in 1937.

Problems with ductography, which involved the injection of a radiographically opaque contrast agent into the nipple, occurred when the early contrast agents, such as oil-based lipiodol, proved to be toxic and capable of causing abscesses.⁷This advance led to the development of other agents, and among the most popular at the time was one that would prove deadly to many.

Thorotrast, first used in 1928, was widely embraced because of its lack of immediately noticeable side effects and the high-quality contrast it provided. Thorotrast was a suspension of radioactive thorium dioxide particles, which gained popularity for use as a radiological imaging agent from the 1930s to 1950s throughout the world, being used in an estimated 2-10 million radiographic exams, primarily for neurosurgery.

In the 1920s and 1930s, world governments had begun to recognize the dangers of radiation exposure, especially among workers, but thorotrast was a unique case because, unbeknownst to most practitioners at the time, thorium dioxide was retained in the body for the lifetime of the patient, with 70% deposited in the liver, 20% in the spleen, and the remaining in the bony medulla and in the peripheral lymph nodes.

Nineteen years after the first use of thorotrast, the first case of a human malignant tumor attributed to its exposure was reported. “Besides the liver neoplasm cases, aplastic anemia, leukemia and an impressive incidence of chromosome aberrations were registered in exposed individuals.”⁸

Despite its widespread adoption elsewhere, especially in Japan, the use of thorotrast never became popular in the United States, in part because in 1932 and 1937, warnings were issued by the American Medical Association to restrict its use.⁹

There was a shift to the use of iodinated hydrophilic molecules as contrast agents for conventional x-ray, computed tomography, and fluoroscopy procedures.⁹ However, it was discovered that these agents, too, have their own risks and dangerous side effects. They can cause severe adverse effects, including allergies, cardiovascular diseases, and nephrotoxicity in some patients.
 

Slow adoption and limited results

Between 1930 and 1950, Dr. Warren, Jacob Gershon-Cohen, MD (1899-1971) of Philadelphia, and radiologist Raul Leborgne of Uruguay “spread the gospel of mammography as an adjunct to physical examination for the diagnosis of breast cancer.”⁴ The latter also developed the breast compression technique to produce better quality images and lower the radiation exposure needed, and described the differences that could be visualized between benign and malign microcalcifications.

But despite the introduction of improvements such as double-emulsion film and breast compression to produce higher-quality images, “mammographic films often remained dark and hazy. Moreover, the new techniques, while improving the images, were not easily reproduced by other investigators and clinicians,” and therefore were still not widely adopted.⁴

Little noticeable effect of mammography

Although the technology existed and had its popularizers, mammography had little impact on an epidemiological level.

There was no major change in the mean maximum breast cancer tumor diameter and node positivity rate detected over the 20 years from 1929 to 1948.10 However, starting in the late 1940s, the American Cancer Society began public education campaigns and early detection education, and thereafter, there was a 3% decline in mean maximum diameter of tumor size seen every 10 years until 1968.

“We have interpreted this as the effect of public education and professional education about early detection through television, print media, and professional publications that began in 1947 because no other event was known to occur that would affect cancer detection beginning in the late 1940s.”¹⁰

However, the early detection methods at the time were self-examination and clinical examination for lumps, with mammography remaining a relatively limited tool until its general acceptance broadened a few decades later.
 

Robert Egan, “Father of Mammography,” et al.

United States. Public Health Service

The broad acceptance of mammography as a screening tool and its impacts on a broad population level resulted in large part from the work of Robert L. Egan, MD (1921-2001) in the late 1950s and 1960s.

Dr. Egan’s work was inspired in 1956 by a presentation by a visiting fellow, Jean Pierre Batiani, who brought a mammogram clearly showing a breast cancer from his institution, the Curie Foundation in Paris. The image had been made using very low kilowattage, high tube currents, and fine-grain film.

Dr. Egan, then a resident in radiology, was given the task by the head of his department of reproducing the results.

In 1959, Dr. Egan, then at the University of Texas MD Anderson Cancer Center, Houston, published a combined technique that used a high-milliamperage–low-voltage technique, a fine-grain intensifying screen, and single-emulsion films for mammography, thereby decreasing the radiation exposure significantly from previous x-ray techniques and improving the visualization and reproducibility of screening.

By 1960, Dr. Egan reported on 1,000 mammography cases at MD Anderson, demonstrating the ability of proper screening to detect unsuspected cancers and to limit mastectomies on benign masses. Of 245 breast cancers ultimately confirmed by biopsy, 238 were discovered by mammography, 19 of which were in women whose physical examinations had revealed no breast pathology. One of the cancers was only 8 mm in diameter when sectioned at biopsy.

Dr. Egan’s findings prompted an investigation by the Cancer Control Program (CCP) of the U.S. Public Health Service and led to a study jointly conducted by the National Cancer Institute and MD Anderson Hospital and the CCP, which involved 24 institutions and 1,500 patients.

“The results showed a 21% false-negative rate and a 79% true-positive rate for screening studies using Egan’s technique. This was a milestone for women’s imaging in the United States. Screening mammography was off to a tentative start.”⁵

“Egan was the man who developed a smooth-riding automobile compared to a Model T. He put mammography on the map and made it an intelligible, reproducible study. In short, he was the father of modern mammography,” according to his professor, mentor, and fellow mammography pioneer Gerald Dodd, MD (Emory School of Medicine website biography).

In 1964 Dr. Egan published his definitive book, “Mammography,” and in 1965 he hosted a 30-minute audiovisual presentation describing in detail his technique.¹¹

The use of mammography was further powered by improved methods of preoperative needle localization, pioneered by Richard H. Gold, MD, in 1963 at Jefferson Medical College, Philadelphia, which eased obtaining a tissue diagnosis for any suspicious lesions detected in the mammogram. Dr. Gold performed needle localization of nonpalpable, mammographically visible lesions before biopsy, which allowed surgical resection of a smaller volume of breast tissue than was possible before.

Throughout the era, there were also incremental improvements in mammography machines and an increase in the number of commercial manufacturers.

Xeroradiography, an imaging technique adapted from xerographic photocopying, was seen as a major improvement over direct film imaging, and the technology became popular throughout the 1970s based on the research of John N. Wolfe, MD (1923-1993), who worked closely with the Xerox Corporation to improve the breast imaging process.⁶ However, this technology had all the same problems associated with running an office copying machine, including paper jams and toner issues, and the worst aspect was the high dose of radiation required. For this reason, it would quickly be superseded by the use of screen-film mammography, which eventually completely replaced the use of both xeromammography and direct-exposure film mammography.
 

The march of mammography

National Cancer Insitute/Bill Branson

A series of nine randomized clinical trials (RCTs) between the 1960s and 1990s formed the foundation of the clinical use of mammography. These studies enrolled more than 600,000 women in the United States, Canada, the United Kingdom, and Sweden. The nine main RCTs of breast cancer screening were the Health Insurance Plan of Greater New York (HIP) trial, the Edinburgh trial, the Canadian National Breast Screening Study, the Canadian National Breast Screening Study 2, the United Kingdom Age trial, the Stockholm trial, the Malmö Mammographic Screening Trial, the Gothenburg trial, and the Swedish Two-County Study.³

These trials incorporated improvements in the technology as it developed, as seen in the fact that the earliest, the HIP trial, used direct-exposure film mammography and the other trials used screen-film mammography.3

Meta-analyses of the major nine screening trials indicated that reduced breast cancer mortality with screening was dependent on age. In particular, the results for women aged 40-49 years and 50-59 years showed only borderline statistical significance, and they varied depending on how cases were accrued in individual trials. “Assuming that differences actually exist, the absolute breast cancer mortality reduction per 10,000 women screened for 10 years ranged from 3 for age 39-49 years; 5-8 for age 50-59 years; and 12-21 for age 60-69 years.”3 In addition the estimates for women aged 70-74 years were limited by low numbers of events in trials that had smaller numbers of women in this age group.

However, at the time, the studies had a profound influence on increasing the popularity and spread of mammography.

As mammographies became more common, standardization became an important issue and a Mammography Accreditation Program began in 1987. Originally a voluntary program, it became mandatory with the Mammography Quality Standards Act of 1992, which required all U.S. mammography facilities to become accredited and certified.

In 1986, the American College of Radiology proposed its Breast Imaging Reporting and Data System (BI-RADS) initiative to enable standardized reporting of mammography; the first report was released in 1993.

BI-RADS is now on its fifth edition and has addressed the use of mammography, breast ultrasonography, and breast magnetic resonance imaging, developing standardized auditing approaches for all three techniques of breast cancer imaging.6
 

The digital era and beyond

With the dawn of the 21st century, the era of digital breast cancer screening began.

The screen-film mammography (SFM) technique employed throughout the 1980s and 1990s had significant advantages over earlier x-ray films for producing more vivid images of dense breast tissues. The next technology, digital mammography, was introduced in the late 20th century, and the first system was approved by the U.S. FDA in 2000.

One of the key benefits touted for digital mammograms is the fact that the radiologist can manipulate the contrast of the images, which allows for masses to be identified that might otherwise not be visible on standard film.

However, the recent meta-analysis discussed in the introduction calls such benefits into question, and a new controversy is likely to ensue on the question of the effectiveness of digital mammography on overall clinical outcomes.

But the technology continues to evolve.

“There has been a continuous and substantial technical development from SFM to full-field digital mammography and very recently also the introduction of digital breast tomosynthesis (DBT). This technical evolution calls for new evidence regarding the performance of screening using new mammography technologies, and the evidence needed to translate new technologies into screening practice,” according to an updated assessment by the U.S. Preventive Services Task Force.¹²

DBT was approved by the Food and Drug Administration in 2011. The technology involves the creation of a series of images, which are assembled into a 3-D–like image of breast slices. Traditional digital mammography creates a 2-D image of a flattened breast, and the radiologist must peer through the layers to find abnormalities. DBT uses a computer algorithm to reconstruct multiple low-dose digital images of the breast that can be displayed individually or in cinematic mode.¹³

Early trials showed a significant benefit of DBT in detecting new and smaller breast cancers, compared with standard digital mammography.

In women in their 40s, DBT found 1.7 more cancers than digital mammography for every 1,000 exams of women with normal breast tissue. In addition, 16.3% of women in this age group who were screened using digital mammography received callbacks, versus 11.7% of those screened using DBT. For younger women with dense breasts, the advantage of DBT was even greater, with 2.27 more cancers found for every 1,000 women screened. Whether such results will lead to clinically improved outcomes remains a question. “It can still miss cancers. Also, like traditional mammography, DBT might not reduce deaths from tumors that are very aggressive and fast-growing. And some women will still be called back unnecessarily for false-positive results.”¹⁴

But such technological advances further the hopes of researchers and patients alike.
 

Conclusion

Medical technology is driven both by advances in science and by the demands of patients and physicians for improved outcomes. The history of mammography, for example, is tied to the scientific advancements in x-ray technology, which allowed physicians for the first time to peer inside a living body without a scalpel at hand. But mammography was also an outgrowth of the profound need of the surgeon to identify cancerous masses in the breast at an early-enough stage to attempt a cure, while simultaneously minimizing the radical nature of the surgery required.

And while seeing is believing, the need to see and verify what was seen in order to make life-and-death decisions drove the demand for improvements in the technology of mammography throughout most of the 20th century and beyond.

The tortuous path from the early and continuing snafus with contrast agents to the apparent failure of the promise of digital technology serves as a continuing reminder of the hopes and perils that developing medical technologies present. It will be interesting to see if further refinements to mammography, such as DBT, will enhance the technology enough to have a major impact on countless women’s lives, or if new developments in magnetic resonance imaging and ultrasound make traditional mammography a relic of the past.

Part 2 of this history will present the social dynamics intimately involved with the rise and promulgation of mammography and how social need and public fears and controversies affected its development and spread as much, if not more, than technological innovation.

This article could only touch upon the myriad of details and technologies involved in the history of mammography, and I urge interested readers to check out the relevant references for far more in-depth and fascinating stories from its complex and controversial past.

mlesney@mdedge.com

References

1. Felix EL, Rosen M, Earle D. “Curbing Our Enthusiasm for Surgical Innovation: Is It a Good Thing or Bad Thing?” The Great Debates, General Surgery News, 2018 Oct 17

2. J Natl Cancer Inst. 2020 Jun 23. doi: 10.1093/jnci/djaa080.

3. Nelson H et al. Screening for Breast Cancer: A Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation. Evidence Synthesis No. 124. (Rockville, Md.: U.S. Agency for Healthcare Research and Quality, 2016 Jan, pp. 29-49)4. Lerner, BH. “To See Today With the Eyes of Tomorrow: A History of Screening Mammography,” background paper for Patlak M et al., Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer (Washington: National Academies Press, 2001).

5. Grady I, Hansen P. Chapter 28: Mammography in “Kuerer’s Breast Surgical Oncology”(New York: McGaw-Hill Medical, 2010)

6. Radiology. 2014 Nov;273(2 Suppl):S23-44.

7. Bassett LW, Kim CH. (2003) Chapter 1: Ductography in Dershaw DD (eds) “Imaging-Guided Interventional Breast Techniques” (New York: Springer, 2003, pp. 1-30).

8. Cuperschmid EM, Ribeiro de Campos TP. 2009 International Nuclear Atlantic Conference, Rio de Janeiro, Sept 27–Oct 2, 2009

9. Bioscience Microflora. 2000;19(2):107-16.

10. Cady B. New era in breast cancer. Impact of screening on disease presentation. Surg Oncol Clin N Am. 1997 Apr;6(2):195-202.

11. Egan R. “Mammography Technique.” Audiovisual presentation. (Washington: U.S. Public Health Service, 1965).

12. Zackrisson S, Houssami N. Chapter 13: Evolution of Mammography Screening: From Film Screen to Digital Breast Tomosynthesis in “Breast Cancer Screening: An Examination of Scientific Evidence” (Cambridge, Mass.: Academic Press, 2016, pp. 323-46).13. Melnikow J et al. Screening for breast cancer with digital breast tomosynthesis. Evidence Synthesis No. 125 (Rockville, Md.: U.S. Agency for Healthcare Research and Quality, 2016 Jan).

14. Newer breast screening technology may spot more cancers. Harvard Women’s Health Watch online, June 2019.

Mark Lesney is the editor of Hematology News and the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has worked as a writer/editor for the American Chemical Society, and has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.

A system designed for resource-limited settings provides rapid cancer profiling and requires “scant” cellular specimens, according to researchers.

The automated image cytometry system is called CytoPAN. In preclinical experiments, CytoPAN provided accurate cancer detection in 1 hour using as few as 50 cells.

In a prospective study of 68 breast cancer patients, CytoPAN detected cancer with 100% accuracy. The receptor subtyping accuracy was 96% for HER2 and 93% for estrogen and progesterone receptors.

Jouha Min, PhD, of Massachusetts General Hospital, Boston, and colleagues reported these findings in Science Translational Medicine.

The authors explained that the CytoPAN system is designed to address one of the biggest cancer challenges in low- and middle-income countries (LMICs), where more than two-thirds of cancer deaths occur: providing rapid, affordable diagnostics that enable patients to obtain locally available treatments.

Unfortunately, because of bottlenecks in specimen acquisition, complex handling logistics, a lack of pathologists, and limited laboratory infrastructure, diagnosis in many LMICs frequently takes months. Cancers typically are not diagnosed until advanced symptoms such as palpable mass lesions, weight loss, and malaise have become manifest.
 

Lesion assessment guides management

For women with suspicion of breast cancer, the authors noted, preoperative assessment of focal lesions for receptor status, presence of invasion, histologic type, and tumor grade are crucial for planning therapeutic management. For physicians to provide, for example, tamoxifen, which is commonly available at low cost in LMICs, they must know a patients’ hormone receptor status.

While core and open surgical biopsies yield abundant tissue for embedding, sectioning, and staining for subsequent histopathological analysis, they entail lengthy work flow and call for expensive instrumentation and a trained workforce, the authors noted.

Fine needle aspirations (FNAs) can be performed by nonphysicians after minimal training with very low complication rates. The much smaller–gauge needles (20-25 gauge) used in FNAs are generally well tolerated, the authors added.

This is why CytoPAN was designed for use with specimens obtained via FNA of palpable mass lesions.
 

Self-contained design

The CytoPAN system was engineered as a self-contained, integrated cytometry platform enabling same-day diagnosis and treatment of breast lesions.

The system was designed to comply with the World Health Organization’s “ASSURED” criteria (affordable, sensitive, specific, user friendly, rapid and robust, equipment free, and deliverable to end users), and to be potentially operable by nonphysicians after brief training.

CytoPAN operators collect cells through minimally invasive FNAs and use lyophilized immunostaining kits with relevant antibodies (not requiring refrigeration). Operators perform imaging using the CytoPAN device, which is then subjected to an automated analysis algorithm with results displayed on a user interface.

CytoPAN classifies detected malignant cells according to four subtypes reflecting estrogen receptor (ER), progesterone receptor (PR), and HER2 status – luminal HER2-negative, luminal HER2-positive, HER2-positive, and triple-negative breast cancer. This is intended to facilitate informed treatment choices (e.g., a selective ER modulator, antiestrogen or aromatase inhibitor for ER/PR-positive patients; an anti-HER2 agent for HER2-positive patients).

The final diagnostic report from a given patient sample includes cancer cell population and molecular subtype distribution. The entire diagnostic procedure takes less than an hour. A repeat biopsy, should the sample be nondiagnostic, can be taken within an hour.
 

Murine, then human testing

A test of CytoPAN on FNA samples from mouse xenografts representing the spectrum of human breast cancer subtypes showed correct and reproducible molecular subtyping that matched well with flow cytometry reports derived from the same tumors.

To determine the clinical utility of CytoPAN, investigators enrolled 68 treatment-naive breast cancer patients who were referred for primary surgery at the Kyungpook National University Chilgok Hospital in Daegu, South Korea. FNA samples were obtained after visualization of breast masses by ultrasound or CT.

Surgical specimens and/or core biopsies were processed by routine pathology for “gold-standard” comparison. FNA samples had sufficient numbers of cells in 63 (93%) patients, with a mean number of cells among them of 1,308 (range, 93-11,985).

CytoPAN analysis correctly identified malignant breast cancer in 55 patients and benign lesions in 5 patients. Three cases were inconclusive because of low numbers of Quad-positive cells for further analysis. The authors pointed out that roughly 20% of biopsy samples in developed countries are deemed “nondiagnostic” because of insufficient cellular contents.

The authors’ summary underscored CytoPAN’s affordable system using cellular rather than tissue specimens, actionable results in an hour, lack of moving parts, multiplexed analysis, and user-friendly interface.

Cancer detection accuracy was 100% (no false negatives or false positives), and receptor subtyping accuracy was 97% for HER2 and 93% for ER/PR.

“Based on these results, we envision prospective clinical trials in remote, decentralized locations,” the authors wrote. The system is being tested further in Botswana.

“I find the data in this paper compelling – particularly for those patients presenting with a palpable mass on clinical exam. ... Certainly in resource-limited settings, this would have significant appeal,” William J. Gradishar, MD, of Northwestern University, Chicago, said in an interview.

Dr. Gradishar explained that, while palpable masses that lead to a diagnosis of noninvasive disease alone are uncommon in the United States because of routine screening mammography, they may still be an issue in other parts of the world.

The authors received funding from the National Institutes of Health, the MGH Scholar Fund, and Robert Wood Johnson Foundation. Some authors disclosed relationships with Akili, Accure Health, ModeRNA, Tarveda, Lumicell, and Noul. Dr. Gradishar reported having no disclosures.

SOURCE: Min J et al. Sci Transl Med. 2020 Aug 5. doi: 10.1126/scitranslmed.aaz9746.

A system designed for resource-limited settings provides rapid cancer profiling and requires “scant” cellular specimens, according to researchers.

The automated image cytometry system is called CytoPAN. In preclinical experiments, CytoPAN provided accurate cancer detection in 1 hour using as few as 50 cells.

In a prospective study of 68 breast cancer patients, CytoPAN detected cancer with 100% accuracy. The receptor subtyping accuracy was 96% for HER2 and 93% for estrogen and progesterone receptors.

Jouha Min, PhD, of Massachusetts General Hospital, Boston, and colleagues reported these findings in Science Translational Medicine.

The authors explained that the CytoPAN system is designed to address one of the biggest cancer challenges in low- and middle-income countries (LMICs), where more than two-thirds of cancer deaths occur: providing rapid, affordable diagnostics that enable patients to obtain locally available treatments.

Unfortunately, because of bottlenecks in specimen acquisition, complex handling logistics, a lack of pathologists, and limited laboratory infrastructure, diagnosis in many LMICs frequently takes months. Cancers typically are not diagnosed until advanced symptoms such as palpable mass lesions, weight loss, and malaise have become manifest.
 

Lesion assessment guides management

For women with suspicion of breast cancer, the authors noted, preoperative assessment of focal lesions for receptor status, presence of invasion, histologic type, and tumor grade are crucial for planning therapeutic management. For physicians to provide, for example, tamoxifen, which is commonly available at low cost in LMICs, they must know a patients’ hormone receptor status.

While core and open surgical biopsies yield abundant tissue for embedding, sectioning, and staining for subsequent histopathological analysis, they entail lengthy work flow and call for expensive instrumentation and a trained workforce, the authors noted.

Fine needle aspirations (FNAs) can be performed by nonphysicians after minimal training with very low complication rates. The much smaller–gauge needles (20-25 gauge) used in FNAs are generally well tolerated, the authors added.

This is why CytoPAN was designed for use with specimens obtained via FNA of palpable mass lesions.
 

Self-contained design

The CytoPAN system was engineered as a self-contained, integrated cytometry platform enabling same-day diagnosis and treatment of breast lesions.

The system was designed to comply with the World Health Organization’s “ASSURED” criteria (affordable, sensitive, specific, user friendly, rapid and robust, equipment free, and deliverable to end users), and to be potentially operable by nonphysicians after brief training.

CytoPAN operators collect cells through minimally invasive FNAs and use lyophilized immunostaining kits with relevant antibodies (not requiring refrigeration). Operators perform imaging using the CytoPAN device, which is then subjected to an automated analysis algorithm with results displayed on a user interface.

CytoPAN classifies detected malignant cells according to four subtypes reflecting estrogen receptor (ER), progesterone receptor (PR), and HER2 status – luminal HER2-negative, luminal HER2-positive, HER2-positive, and triple-negative breast cancer. This is intended to facilitate informed treatment choices (e.g., a selective ER modulator, antiestrogen or aromatase inhibitor for ER/PR-positive patients; an anti-HER2 agent for HER2-positive patients).

The final diagnostic report from a given patient sample includes cancer cell population and molecular subtype distribution. The entire diagnostic procedure takes less than an hour. A repeat biopsy, should the sample be nondiagnostic, can be taken within an hour.
 

Murine, then human testing

A test of CytoPAN on FNA samples from mouse xenografts representing the spectrum of human breast cancer subtypes showed correct and reproducible molecular subtyping that matched well with flow cytometry reports derived from the same tumors.

To determine the clinical utility of CytoPAN, investigators enrolled 68 treatment-naive breast cancer patients who were referred for primary surgery at the Kyungpook National University Chilgok Hospital in Daegu, South Korea. FNA samples were obtained after visualization of breast masses by ultrasound or CT.

Surgical specimens and/or core biopsies were processed by routine pathology for “gold-standard” comparison. FNA samples had sufficient numbers of cells in 63 (93%) patients, with a mean number of cells among them of 1,308 (range, 93-11,985).

CytoPAN analysis correctly identified malignant breast cancer in 55 patients and benign lesions in 5 patients. Three cases were inconclusive because of low numbers of Quad-positive cells for further analysis. The authors pointed out that roughly 20% of biopsy samples in developed countries are deemed “nondiagnostic” because of insufficient cellular contents.

The authors’ summary underscored CytoPAN’s affordable system using cellular rather than tissue specimens, actionable results in an hour, lack of moving parts, multiplexed analysis, and user-friendly interface.

Cancer detection accuracy was 100% (no false negatives or false positives), and receptor subtyping accuracy was 97% for HER2 and 93% for ER/PR.

“Based on these results, we envision prospective clinical trials in remote, decentralized locations,” the authors wrote. The system is being tested further in Botswana.

“I find the data in this paper compelling – particularly for those patients presenting with a palpable mass on clinical exam. ... Certainly in resource-limited settings, this would have significant appeal,” William J. Gradishar, MD, of Northwestern University, Chicago, said in an interview.

Dr. Gradishar explained that, while palpable masses that lead to a diagnosis of noninvasive disease alone are uncommon in the United States because of routine screening mammography, they may still be an issue in other parts of the world.

The authors received funding from the National Institutes of Health, the MGH Scholar Fund, and Robert Wood Johnson Foundation. Some authors disclosed relationships with Akili, Accure Health, ModeRNA, Tarveda, Lumicell, and Noul. Dr. Gradishar reported having no disclosures.

SOURCE: Min J et al. Sci Transl Med. 2020 Aug 5. doi: 10.1126/scitranslmed.aaz9746.

A system designed for resource-limited settings provides rapid cancer profiling and requires “scant” cellular specimens, according to researchers.

The automated image cytometry system is called CytoPAN. In preclinical experiments, CytoPAN provided accurate cancer detection in 1 hour using as few as 50 cells.

In a prospective study of 68 breast cancer patients, CytoPAN detected cancer with 100% accuracy. The receptor subtyping accuracy was 96% for HER2 and 93% for estrogen and progesterone receptors.

Jouha Min, PhD, of Massachusetts General Hospital, Boston, and colleagues reported these findings in Science Translational Medicine.

The authors explained that the CytoPAN system is designed to address one of the biggest cancer challenges in low- and middle-income countries (LMICs), where more than two-thirds of cancer deaths occur: providing rapid, affordable diagnostics that enable patients to obtain locally available treatments.

Unfortunately, because of bottlenecks in specimen acquisition, complex handling logistics, a lack of pathologists, and limited laboratory infrastructure, diagnosis in many LMICs frequently takes months. Cancers typically are not diagnosed until advanced symptoms such as palpable mass lesions, weight loss, and malaise have become manifest.
 

Lesion assessment guides management

For women with suspicion of breast cancer, the authors noted, preoperative assessment of focal lesions for receptor status, presence of invasion, histologic type, and tumor grade are crucial for planning therapeutic management. For physicians to provide, for example, tamoxifen, which is commonly available at low cost in LMICs, they must know a patients’ hormone receptor status.

While core and open surgical biopsies yield abundant tissue for embedding, sectioning, and staining for subsequent histopathological analysis, they entail lengthy work flow and call for expensive instrumentation and a trained workforce, the authors noted.

Fine needle aspirations (FNAs) can be performed by nonphysicians after minimal training with very low complication rates. The much smaller–gauge needles (20-25 gauge) used in FNAs are generally well tolerated, the authors added.

This is why CytoPAN was designed for use with specimens obtained via FNA of palpable mass lesions.
 

Self-contained design

The CytoPAN system was engineered as a self-contained, integrated cytometry platform enabling same-day diagnosis and treatment of breast lesions.

The system was designed to comply with the World Health Organization’s “ASSURED” criteria (affordable, sensitive, specific, user friendly, rapid and robust, equipment free, and deliverable to end users), and to be potentially operable by nonphysicians after brief training.

CytoPAN operators collect cells through minimally invasive FNAs and use lyophilized immunostaining kits with relevant antibodies (not requiring refrigeration). Operators perform imaging using the CytoPAN device, which is then subjected to an automated analysis algorithm with results displayed on a user interface.

CytoPAN classifies detected malignant cells according to four subtypes reflecting estrogen receptor (ER), progesterone receptor (PR), and HER2 status – luminal HER2-negative, luminal HER2-positive, HER2-positive, and triple-negative breast cancer. This is intended to facilitate informed treatment choices (e.g., a selective ER modulator, antiestrogen or aromatase inhibitor for ER/PR-positive patients; an anti-HER2 agent for HER2-positive patients).

The final diagnostic report from a given patient sample includes cancer cell population and molecular subtype distribution. The entire diagnostic procedure takes less than an hour. A repeat biopsy, should the sample be nondiagnostic, can be taken within an hour.
 

Murine, then human testing

A test of CytoPAN on FNA samples from mouse xenografts representing the spectrum of human breast cancer subtypes showed correct and reproducible molecular subtyping that matched well with flow cytometry reports derived from the same tumors.

To determine the clinical utility of CytoPAN, investigators enrolled 68 treatment-naive breast cancer patients who were referred for primary surgery at the Kyungpook National University Chilgok Hospital in Daegu, South Korea. FNA samples were obtained after visualization of breast masses by ultrasound or CT.

Surgical specimens and/or core biopsies were processed by routine pathology for “gold-standard” comparison. FNA samples had sufficient numbers of cells in 63 (93%) patients, with a mean number of cells among them of 1,308 (range, 93-11,985).

CytoPAN analysis correctly identified malignant breast cancer in 55 patients and benign lesions in 5 patients. Three cases were inconclusive because of low numbers of Quad-positive cells for further analysis. The authors pointed out that roughly 20% of biopsy samples in developed countries are deemed “nondiagnostic” because of insufficient cellular contents.

The authors’ summary underscored CytoPAN’s affordable system using cellular rather than tissue specimens, actionable results in an hour, lack of moving parts, multiplexed analysis, and user-friendly interface.

Cancer detection accuracy was 100% (no false negatives or false positives), and receptor subtyping accuracy was 97% for HER2 and 93% for ER/PR.

“Based on these results, we envision prospective clinical trials in remote, decentralized locations,” the authors wrote. The system is being tested further in Botswana.

“I find the data in this paper compelling – particularly for those patients presenting with a palpable mass on clinical exam. ... Certainly in resource-limited settings, this would have significant appeal,” William J. Gradishar, MD, of Northwestern University, Chicago, said in an interview.

Dr. Gradishar explained that, while palpable masses that lead to a diagnosis of noninvasive disease alone are uncommon in the United States because of routine screening mammography, they may still be an issue in other parts of the world.

The authors received funding from the National Institutes of Health, the MGH Scholar Fund, and Robert Wood Johnson Foundation. Some authors disclosed relationships with Akili, Accure Health, ModeRNA, Tarveda, Lumicell, and Noul. Dr. Gradishar reported having no disclosures.

SOURCE: Min J et al. Sci Transl Med. 2020 Aug 5. doi: 10.1126/scitranslmed.aaz9746.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.