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A Banned Chemical That Is Still Causing Cancer
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Active Surveillance for Cancer Doesn’t Increase Malpractice Risk
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
Women’s Cancers: Clinicians Research, Advise on Sexual Dysfunction
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
Decreased sexual function is a side effect of many types of cancer, notably uterine, cervical, ovarian, and breast cancer, that often goes unaddressed, according to the authors of several studies presented at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer.
Patients want to talk about sex, but not necessarily at the start of their diagnosis or treatment, suggest the findings of a study presented at the meeting. Jesse T. Brewer of Weill Cornell Medicine in New York City and colleagues enrolled 63 patients who underwent surgery with documented hereditary breast cancer, ovarian cancer, or Lynch syndrome in a cross-sectional survey.
Overall, 86% said that sexuality and intimacy were very or somewhat important, and 78% said that the healthcare team addressing the issue was very or somewhat important, the researchers found. However, only 40% of the respondents said that they wanted to discuss sexuality at the time of diagnosis because the idea was too overwhelming.
Oncologists are more aware of sexual side effects and the potential for sexual issues that persist long after treatment, but many patients may not have opportunities to talk about sexual concerns, said Don S. Dizon, MD, an oncologist specializing in women’s cancers at Brown University, Providence, Rhode Island, in an interview.
“It is important that we [oncologists] be the ones to open the door to these conversations; people with cancer will not bring it up spontaneously, for fear of making their provider uncomfortable, especially if they’ve never been asked about it before,” Dr. Dizon said in an interview.
He advised clinicians to find a network within their health systems so they can refer patients to specialized services, such as sex therapy, couples counseling, pelvic rehabilitation, or menopausal experts as needed.
In another study presented at the meeting, Naaman Mehta, MD, of NYU Langone Health, and colleagues reviewed data from 166 healthcare providers who completed a 23-item survey about evaluating and managing sexual health concerns of their patients. Most of the respondents were gynecologic oncologists (93.4%), but one radiation oncologist and 10 other healthcare providers also completed the survey.
Overall, approximately 60% of the respondents routinely asked about the sexual health concerns of their patients, and 98% of these said they believed that sexual health discussions should be held with a gynecologic oncologist. Just over half (54%) also said that the patient should be the one to initiate a discussion of sexual health concerns.
Female providers were significantly more likely to discuss sexual health with patients, compared with male providers, after controlling for the hospital setting and training level, the researchers noted (odds ratio, 1.4;P < .01).
The results suggest a need for more ways to integrate sexual health screening into gynecologic oncologic clinics, the researchers concluded.
The provider survey findings are similar to the results of a survey conducted by Dr. Dizon and colleagues in 2007. In that study, less than half of respondents took a sexual history, but 80% felt there was insufficient time to explore sexual issues.
“It is critical to understand that people with cancer do not expect their oncologists to be sexual health experts, but as with all other side effects caused by treatment and the diagnosis, we can be the ones who recognize it,” Dr. Dizon noted, in an interview.
Common Complaints and Causes
In Dr. Dizon’s experience, local symptoms including vaginal dryness, pain with penetration, and vaginal thinning, are common sexual complaints in women with cancer, as are systemic issues such as lack of interest and menopause-type symptoms.
“For those undergoing radiation, the vaginal tunnel can actually develop adhesions, and if not treated proactively this can lead to vaginal stenosis,” said Dr. Dizon, who was not involved in the studies presented at the meeting.
Comorbidities such as diabetes, cardiovascular disease, and musculoskeletal conditions can contribute to sexual issues in women with cancer, according to Nora Lersch, DNP, FNP-BC, AOCNP, and Nicole Dreibelbis, CRNP, the authors of other research presented at the meeting.
Culture, religion, fitness level, history of sexual violence, and gender spectrum health also play a role, as do anxiety and depression, dementia, and substance abuse disorders, the authors wrote in their presentation, “Prioritizing Sexual Health in Gynecological Oncology Care.”
Low libido is a frequent complaint across all cancer types, Ms. Dreibelbis, a nurse practitioner specializing in gynecologic oncology at the UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, said in an interview.
“Breast cancer patients, especially those on [aromatase inhibitor] therapy, often experience vaginal dryness and therefore dyspareunia,” she added.
The pelvic floor muscles, with their important role in sexual response, can be weakened by cancer treatment or surgery, and the pudendal nerves, which are the primary nerves responsible for sexual response in women, can be affected as well, Dr. Lersch and Ms. Dreibelbis wrote.
Taking Sex Seriously
Researchers are exploring the impact of different cancer prevention treatments for women to mitigate sexual side effects, as illustrated by another study presented at the meeting.
Dr. Barbara Norquist, MD, a gynecologic oncologist at the University of Washington, Seattle, and colleagues compared the sexual function and menopausal symptoms of patients at high risk of ovarian carcinoma who underwent either interval salpingectomy/delayed oophorectomy (ISDO) or risk-reducing salpingo-oophorectomy (RRSO).
“For patients at high risk for ovarian cancer, surgical removal of the tubes and ovaries is the mainstay of prevention, as screening is not effective at reducing death from ovarian cancer. As a result of surgery, many patients become suddenly postmenopausal from losing their ovaries,” Dr. Norquist said in an interview.
Some patients delay surgery out of concern for health and quality of life, including sexual function, she said.
In the study (known as the WISP trial) the researchers compared data from 166 patients who underwent immediate removal of the fallopian tubes and ovaries and 171 who underwent fallopian tube removal and delayed oophorectomy. All patients completed questionnaires about sexual function. The primary outcome was change in sexual function based on the sexual function index (FSFI) from baseline to 6 months after surgery.
Overall, changes in sexual function were significantly greater in the immediate oophorectomy group, compared with the delayed oophorectomy group at 6 months (33% vs 17%) and also at 12 months (43% vs 20%).
A further review of patients using hormone therapy showed that those in the immediate oophorectomy group still had greater decreases in sexual function, compared with the delayed group, though the difference between groups of patients using hormone therapy was less dramatic.
“I was surprised that, even with hormone replacement therapy, patients undergoing removal of the ovaries still had significant detrimental changes to sexual function when compared to those having the tubes removed, although this was even worse in those who could not take HRT,” Dr. Norquist said, in an interview. “I was reassured that menopausal symptoms in general were well managed with HRT, as these patients did not score differently on menopause symptoms, compared with those having their tubes removed,” she said.
Patients deserve accurate information about predicted changes in menopausal symptoms and sexual function as a result of ovary removal, and HRT should be provided when there is no contraindication, Dr. Norquist told this news organization.
Dr. Norquist and colleagues are awaiting the results of clinical trials investigating the safety of salpingectomy with delayed oophorectomy in terms of ovarian cancer prevention, but more research is needed to identify optimal management of the menopausal and sexual side effects associated with surgical menopause, she noted.
“Findings from the WISP study show the importance of hormones in women undergoing prophylactic surgery,” Dr. Dizon said. The findings indicate that salpingectomy has less of a negative influence on sexual function compared to removal of the ovaries, and the impact of hormone therapy and the relatively young age of the patients who took hormones reinforces current knowledge about hormones and sex, he added.
Barriers and Solutions
Barriers to asking women with cancer about sexual issues reported by providers include limited time, lack of training in sexual health, a desire to avoid offending the patient or making them uncomfortable, and uncertainty about how to answer the questions, Dr. Lersch and Ms. Dreibelbis wrote in their presentation.
Barriers to asking healthcare providers about their sexual issues reported by patients include the beliefs that the clinician should initiate the discussion, that sexual function will not be taken seriously, and that they might make the provider uncomfortable.
“Fortunately, more information and research has been done on sexual health and gynecological cancer in recent years, so oncologists are becoming more aware of the issues women may have,” said Dr. Lersch who is an oncology nurse practitioner at Providence Franz Cancer Institute in Portland, Oregon, in an interview.
Telling patients early in their cancer treatment about potential sexual side effects and opportunities for help is essential, she added.
Although oncologists have become more aware of the importance of sexual health and well-being for their patients, “I think there has historically been a disconnect in including sexual health education in medical training,” Ms. Dreibelbis said in an interview.
Dr. Lersch and Ms. Dreibelbis advised a multidimensional approach to managing sexual problems in cancer patients that includes consideration of biological and psychological symptoms, but also social, cultural, and interpersonal factors, in their presentation.
Their suggestions include discussing dyspareunia with their patients, asking for details such as whether the pain is internal or external, whether it occurs with activities outside of sex including masturbation, and whether bleeding is present.
Oncology therapies and surgeries can decrease or eliminate an individual’s ability to produce their own lubricant; for example, removal of the cervix eliminates cervical mucous, which helps with internal lubrication, they wrote in their presentation.
For patients with dyspareunia, Dr. Lersch and Ms. Dreibelbis recommend a vaginal moisturizer especially formulated for vaginal tissue that can be absorbed by the mucosal tissue of the vagina. Use of this type of product can increase the effectiveness of lubricants and help restore integrity of the vaginal tissue. Such moisturizers are available as gels, creams, or suppositories over the counter, and do not contain hormones.
Vaginal estrogen can be helpful for burning, itching, irritation, tissue fragility, and pain with sex, according to Dr. Lersch and Ms. Dreibelbis. Adequate estrogen therapy can promote normalization of vaginal pH and microflora, as well increase vaginal secretion and reduce pain and dryness with intercourse, the presenters stated in their presentation. In addition, dilator therapy can be used to help prevent vaginal stenosis, and penetration bumpers can help relieve discomfort during intercourse, they wrote.
Looking ahead, more research is needed to serve a wider patient population, Ms. Dreibelbis said, in an interview.
“LGBTQIA [individuals] have not been included in sexual health research and there are more people than ever who identify within this group of people. I know there has also been some very early work on shielding the clitoris from the impacts of radiation, and I believe this is extremely important up-and-coming research,” she said.
Dr. Lersch, Ms. Dreibelbi, Dr. Dizon, Dr. Norquist, Ms. Brewer, and Dr. Mehta had no financial conflicts to disclose.
FROM SGO 2024
Commentary: MRI Surveillance and Risk Factors in Breast Cancer, April 2024
A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.
Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to a higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further understand the differences within this subtype itself.
Additional References
- National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source
- Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): A multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X Source
- Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
- Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
- Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
- Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source
A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.
Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to a higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further understand the differences within this subtype itself.
Additional References
- National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source
- Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): A multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X Source
- Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
- Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
- Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
- Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source
A positive family history of cancer and obesity are established risk factors for development of breast cancer among women.[4,5] A population-based cohort study that included 15,055 Chinese women evaluated the association and interaction between body mass index (BMI) and family history of cancer on the risk for breast cancer (Cao et al). The incidence risk for breast cancer was highest in the group with obesity vs the group with normal weight (adjusted HR 2.09; 95% CI 1.42-3.07), and those with a family history of cancer also had an increased risk vs those without a family history of cancer (adjusted HR 1.63; 95% CI 1.22-2.49). Furthermore, women with a BMI ≥ 24 and family history of cancer had a higher risk for breast cancer development compared with women with a BMI < 24 and no family history of cancer (adjusted HR 2.06; 95% CI 1.39-3.06). This study indicates a heightened breast cancer risk when cancer family history and obesity coexist, suggesting the importance of addressing modifiable risk factors and targeting lifestyle interventions in this population.
Triple-negative breast cancer (TNBC), although exhibiting its own heterogeneity, has various features that differentiate this subtype from luminal breast cancers. For example, TNBC generally has a more aggressive course, increased responsiveness to chemotherapy, and earlier pattern of recurrence compared with hormone receptor–positive disease. Prior studies have also shown that established breast cancer risk factors reflect those for the luminal A subtype, whereas those for TNBC are less consistent.[6] A meta-analysis that included 33 studies evaluated the association between traditional breast cancer risk factors and TNBC incidence (Kumar et al). Family history (odds ratio [OR] 1.55; 95% CI 1.34-1.81; P < .001), longer duration of oral contraceptive use (OR 1.29; 95% CI 1.08-1.55; P < .001), and higher breast density (OR 2.19; 95% CI 1.67-2.88; P < .001) were significantly associated with an increased risk for TNBC. Factors including later age at menarche, later age at first birth, and breastfeeding were associated with reduced risk for TNBC. Furthermore, there was no significant association with parity, menopausal hormone therapy, alcohol, smoking, and BMI. This study highlights distinct risk factors that may contribute to a higher risk for TNBC, and future research will be valuable to better elucidate the mechanisms at play and to further understand the differences within this subtype itself.
Additional References
- National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. Source
- Saadatmand S, Geuzinge HA, Rutgers EJT, et al; on behalf of the FaMRIsc study group. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): A multicentre, randomised, controlled trial. Lancet Oncol. 2019;20:1136-1147. doi: 10.1016/S1470-2045(19)30275-X Source
- Warner E, Zhu S, Plewes DB, et al. Breast cancer mortality among women with a BRCA1 or BRCA2 mutation in a magnetic resonance imaging plus mammography screening program. Cancers (Basel). 2020;12:3479. doi: 10.3390/cancers12113479 Source
- Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, et al. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378-397. doi: 10.3322/caac.21405 Source
- Engmann NJ, Golmakani MK, Miglioretti DL, et al; for the Breast Cancer Surveillance Consortium. Population-attributable risk proportion of clinical risk factors for breast cancer. JAMA Oncol. 2017;3:1228-1236. doi: 10.1001/jamaoncol.2016.6326 Source
- Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta Rev Cancer. 2015;1856:73-85. doi: 10.1016/j.bbcan.2015.0002 Source
New Guidance for the Treatment of Metastatic Breast Cancer
The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.
Where do the ABC International Consensus Guidelines come from?
The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?
Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
Can you tell me about the other issues discussed in the guidelines besides drugs?
For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?
The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.
Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.
We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.
We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
The ABC Guidelines discuss tough clinical situations. Can you explain?
The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.
It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
What other tough clinical situations do you discuss in the new guidelines?
We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.
It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.
Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.
We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?
A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.
It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.
Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.
We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.
Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.
Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?
In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.
Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.
The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.
Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.
Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.
A version of this article appeared on Medscape.com.
The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.
Where do the ABC International Consensus Guidelines come from?
The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?
Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
Can you tell me about the other issues discussed in the guidelines besides drugs?
For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?
The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.
Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.
We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.
We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
The ABC Guidelines discuss tough clinical situations. Can you explain?
The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.
It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
What other tough clinical situations do you discuss in the new guidelines?
We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.
It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.
Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.
We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?
A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.
It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.
Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.
We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.
Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.
Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?
In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.
Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.
The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.
Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.
Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.
A version of this article appeared on Medscape.com.
The Advanced Breast Cancer (ABC) 7th International Consensus Conference Guidelines for Advanced Breast Cancer will soon be released. This news organization discussed the new guidelines with Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal. Dr. Cardoso is president of the ABC Global Alliance and chair of the guidelines committee. The interview has been edited for length and clarity.
Where do the ABC International Consensus Guidelines come from?
The 7th International Consensus Conference for Advanced Breast Cancer was held in November 2023. This is an international conference that takes place every 2 years. At the conference, we discuss new data that have come out in the past 2 years regarding advanced and metastatic breast cancer, and whether they should impact the guidelines or not. We look at whether there is any new treatment that is ready for clinical practice that wasn’t available 2 years ago. We look at whether there is anything else that has changed in the past 2 years.
How do the ABC International Consensus Guidelines differ from other guidelines, such as those from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), or the European Society for Medical Oncology (ESMO)?
Patients and patient advocates are members of the consensus panel where we discuss important issues around this disease and how to manage it. We also do not discuss drugs exclusively because there are other needs for patients with advanced breast cancer, and we issue recommendations regarding the global care of these patients.
Can you tell me about the other issues discussed in the guidelines besides drugs?
For example, in the more general recommendations, we revisited the proper definition of endocrine resistance. A lot of clinical trials are based on selecting a population that is considered to be endocrine sensitive or endocrine resistant, but the definition is very heterogeneous. We have updated the definition because there have been quite a few advances in this particular subtype of cancer. This [new] definition of endocrine resistance and sensitivity will be used and implemented in the different clinical trials, allowing for a better interpretation of the results, with clear impact on clinical practice.
What subtype of metastatic breast cancer had the biggest advances in terms of drugs in the guidelines?
The subtype that had the biggest advances in the new guidelines is the hormonal-dependent breast cancer, the ER-positive, HER2-negative. For that particular subtype, we have new drugs either already approved or in the process of being evaluated. Some of them have been approved in the United States but not yet in Europe by the European Medicines Agency (EMA). We are starting to discuss whether these drugs should be approved, and if they are, how we should use them. It is relevant to know what the cost-effectiveness is of each new treatment, as well and the balance between efficacy and toxicity. Sometimes data are too preliminary and we need longer follow-up or more important endpoints, such as survival.
Elacestrant is one of the drugs that has been approved by the US Food and Drug Administration (FDA), and it is very controversial because the benefit it provides on progression-free survival is modest and we still lack data on survival. So, there was a discussion on whether to consider this drug as an option or wait until we have survival data. The majority on the panel thought we could consider elacestrant as a potential new option, when we do not have other endocrine options available.
We issued a recommendation on a drug that is not FDA approved because we think the FDA is going to approve it quite soon. The drug is capivasertib and it blocks the PIK3CA pathway. [Editor’s note: The drug has since been approved by the FDA.] We have a drug that targets this pathway, alpelisib, but it is quite toxic so it is not widely used. Capivasertib has a better toxicity profile so we believe it could be a good addition to our armamentarium for this particular subtype of breast cancer.
We have lots of new data about the antibody-drug conjugates, the ADCs. Initially, we had more data for HER2-positive and triple-negative disease, but now studies have been done to show the value of the ADCs also in the ER-positive, HER2-negative subtype, and so they are now options. In particular, we have trastuzumab deruxtecan for patients with HER2-low disease. Most of the HER2-low tumors are also hormone receptor–positive.
The ABC Guidelines discuss tough clinical situations. Can you explain?
The guidelines also discuss issues that in clinical practice are quite difficult because we don’t have strong data. There are certain tough clinical situations. One example is how to treat a woman who has metastatic disease and is pregnant. We discuss the possibilities of treatment in that situation and also what other support these patients need. We discussed that the only available therapy we can use is chemotherapy. We cannot use endocrine therapy, nor biological agents such as anti-HER2 agents and immunotherapy. So, this raises a lot of concerns for how to treat these women without hurting the fetus. But in these guidelines, we discuss other needs of these patients. It’s a hot topic in the US and we did issue a recommendation: that in some situations where the life of the mother may be at risk because we are not able to provide the most adequate treatment, then they should be free to choose to terminate the pregnancy.
It is important to realize that you can’t give most of the new treatments — and ones that have an impact on survival — to a woman when she is pregnant.
What other tough clinical situations do you discuss in the new guidelines?
We discuss someone who has metastatic disease and is HIV-positive. Can we use CDK4/6 inhibitors? Can we use immunotherapy? What are the recent data? We have very little data to show that we can possibly use immunotherapy, but we do not have any safety data regarding the CDK4/6 inhibitors.
It’s important to note that people who are HIV-positive tend to have a worse mortality rate from cancer and also suffer from more toxicity. Very often, there is a need to reduce the doses of the treatments we are going to give. The guidelines provide guidance on these issues so that in clinical practice, doctors can have some help managing these difficult situations.
Another example of a tough clinical situation is how to treat an elderly, frail patient who has metastatic disease. We discuss what geriatric evaluations you need to perform before deciding the treatment. We discuss the need very often to reduce the starting dose and then adapt according to what the patient can tolerate.
We have discussed quite a lot of topics that are really patient-oriented and clinically oriented. The aim is to help everyone in clinical practice to provide the best available care.
Do you want to expand a bit on the elderly, frail patient and what you have in the guidelines about that?
A very important message is that it doesn’t matter what age your ID card says; it’s the biological age that is important. There are some people who are in their 80s, but they are very fit and they have a very active, normal life. There are other people who are in their 50s and they struggle. It’s important to perform a geriatric evaluation to determine the probability of tolerating a cancer treatment, and we normally use a simple tool called G8. If this tool shows fragility, then it is crucial to have a full geriatric assessment and a full physical exam.
It’s also very important to look for drug-drug interactions in the elderly because these patients often take many different therapies for other diseases.
Another issue is chronic undertreatment in the elderly. If you look just at chronological age and you don’t provide the optimal treatment, there will be increased mortality.
We also recommend starting elderly patients on a lower dose. There are not strong data for that, but we think it is clinical common sense to start at a lower dose. Then, if there is good tolerance, you can move to the usual dose.
Often, the elderly are excluded from clinical trials. Some of the clinical trials for some of the newer agents have included elderly patients. For example, there were some elderly patients in the CDK4/6 inhibitor trials. We know that these patients can receive these treatments with a reduction in dose.
Very frail elderly patients are often excluded from clinical trials. If we continue to do that, we will never know how to treat them.
Is there anything you would like to add about the ABC Guidelines that we haven’t talked about?
In the general statement of the guidelines, we mention two things that I think are important for people to know. The first is that during the COVID-19 pandemic, a lot of cancer patients, particularly those with advanced disease, were not offered access to ventilators. Remember, we didn’t have enough ventilators for everyone, so there were exclusion criteria, and one of the exclusion criteria was having cancer. Cancer patients shouldn’t be excluded from having life-saving treatment based solely on the cancer diagnosis. There are many different cancers and many different stages of the disease.
Access to intensive care units is sometimes needed temporarily for a patient with advanced breast cancer. The new treatments, such as immunotherapies and ADCs, can have significant and life-threatening toxicities. You can die from some of these side effects. All over the world, this is a difficult situation because of the bias among many healthcare providers regarding access to intensive care units for cancer patients. It’s a bias we are fighting against.
The second thing we discuss in the beginning of the new guidelines is what is happening to cancer patients during periods of war or conflict. For example, in Ukraine, many of the patients were able to run away and go to another country, but all their health information was lost because the hospitals were destroyed. Patients arrive in a new country and they don’t have any information on the type of cancer they have nor the type of treatment they were undergoing. It was very difficult, for example, for the doctors in Poland to know how to continue to treat the Ukrainian patients. So, in the guidelines, we discuss how we can find a way to ensure that a patient has a copy of their important health data.
Dr. Cardoso, MD, has disclosed the following relevant financial relationships:Personal financial interest in form of consultancy role for: Amgen; Astellas/Medivation; AstraZeneca; Celgene; Daiichi-Sankyo; Eisai; GE Oncology; Genentech; Gilead; GlaxoSmithKline; Iqvia; Macrogenics; Medscape; Merck-Sharp; Merus BV; Mylan; Mundipharma; Novartis; Pfizer; Pierre-Fabre; prIME Oncology; Roche; Sanofi; Samsung Bioepis; Seagen; Teva; Touchime.
Institutional financial support for clinical trials from: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Bayer; Daiichi; Eisai; Fresenius GmbH; Genentech; GlaxoSmithKline; Ipsen; Incyte; Nektar Therapeutics; Nerviano; Novartis; Macrogenics; Medigene; MedImmune; Merck; Millennium; Pfizer; Pierre-Fabre; Roche; Sanofi-Aventis; Sonus; Tesaro; Tigris; Wilex; Wyeth.
A version of this article appeared on Medscape.com.
Few Childhood Cancer Survivors Get Recommended Screenings
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
New Transparent AI Predicts Breast Cancer 5 Years Out
A new way of using artificial intelligence (AI) can predict breast cancer 5 years in advance with impressive accuracy — and unlike previous AI models, we know how this one works.
The new AI system, called AsymMirai, simplifies previous models by solely comparing differences between right and left breasts to predict risk. It could potentially save lives, prevent unnecessary testing, and save the healthcare system money, its creators say.
“With traditional AI, you ask it a question and it spits out an answer, but no one really knows how it makes its decisions. It’s a black box,” said Jon Donnelly, a PhD student in the department of computer science at Duke University, Durham, North Carolina, and first author on a new paper in Radiology describing the model.
“With our approach, people know how the algorithm comes up with its output so they can fact-check it and trust it,” he said.
One in eight women will develop invasive breast cancer, and 1 in 39 will die from it. Mammograms miss about 20% of breast cancers. (The shortcomings of genetic screening and mammograms received extra attention recently when actress Olivia Munn disclosed that she’d been treated for an aggressive form of breast cancer despite a normal mammogram and a negative genetic test.)
The model could help doctors bring the often-abstract idea of AI to the bedside in a meaningful way, said radiologist Vivianne Freitas, MD, assistant professor of medical imaging at the University of Toronto.
“This marks a new chapter in the field of AI,” said Dr. Freitas, who authored an editorial lauding the new paper. “It makes AI more tangible and understandable, thereby improving its potential for acceptance.”
AI as a Second Set of Eyes
Mr. Donnelly described AsymMirai as a simpler, more transparent, and easier-to-use version of Mirai, a breakthrough AI model which made headlines in 2021 with its promise to determine with unprecedented accuracy whether a patient is likely to get breast cancer within the next 5 years.
Mirai identified up to twice as many future cancer diagnoses as the conventional risk calculator Tyrer-Cuzick. It also maintained accuracy across a diverse set of patients — a notable plus for two fields (AI and healthcare) notorious for delivering poorer results for minorities.
Tyrer-Cuzick and other lower-tech risk calculators use personal and family history to statistically calculate risk. Mirai, on the other hand, analyzes countless bits of raw data embedded in a mammogram to decipher patterns a radiologist’s eyes may not catch. Four images, including two angles from each breast, are fed into the model, which produces a score between 0 and 1 to indicate the person’s risk of getting breast cancer in 1, 3, or 5 years.
But even Mirai’s creators have conceded they didn’t know exactly how it arrives at that score — a fact that has fueled hesitancy among clinicians.
Study coauthor Fides Schwartz, MD, a radiologist at Brigham and Women’s Hospital, Boston, said researchers were able to crack the code on Mirai’s “black box,” finding that its scores were largely determined by assessing subtle differences between right breast tissue and left breast tissue.
Knowing this, the research team simplified the model to predict risk based solely on “local bilateral dissimilarity.” AsymMirai was born.
The team then used AsymMirai to look back at > 200,000 mammograms from nearly 82,000 patients. They found it worked nearly as well as its predecessor, assigning a higher risk to those who would go on to develop cancer 66% of the time (vs Mirai’s 71%). In patients where it noticed the same asymmetry multiple years in a row it worked even better, with an 88% chance of giving people who would develop cancer later a higher score than those who would not.
“We found that we can, with surprisingly high accuracy, predict whether a woman will develop cancer in the next 1-5 years based solely on localized differences between her left and right breast tissue,” said Mr. Donnelly.
Dr. Schwartz imagines a day when radiologists could use the model to help develop personalized screening strategies for patients. Doctors might advise those with higher scores to get screened more often than guidelines suggest, supplement mammograms with an MRI , and keep a close watch on trouble spots identified by AI.
“For people with really low risk, on the other hand, maybe we can save them an annual exam that’s not super pleasant and might not be necessary,” said Dr. Schwartz.
Cautious Optimism
Robert Smith, PhD, senior vice president of early cancer detection science at the American Cancer Society, noted that AI has been used for decades to try to reduce radiologists’ workload and improve diagnoses.
“But AI just never really lived up to its fullest potential,” Dr. Smith said, “quite often because it was being used as a crutch by inexperienced radiologists who, instead of interpreting the mammogram and then seeing what AI had to say ended up letting AI do most of the work which, frankly, just wasn’t that accurate.”
He’s hopeful that newer, more sophisticated iterations of AI medical imaging platforms (roughly 18-20 models are in development) can ultimately save women’s lives, particularly in areas where radiologists are in short supply.
But he believes it will be a long time before doctors, or their patients, are willing to risk postponing a mammogram based on an algorithm.
A version of this article appeared on Medscape.com.
A new way of using artificial intelligence (AI) can predict breast cancer 5 years in advance with impressive accuracy — and unlike previous AI models, we know how this one works.
The new AI system, called AsymMirai, simplifies previous models by solely comparing differences between right and left breasts to predict risk. It could potentially save lives, prevent unnecessary testing, and save the healthcare system money, its creators say.
“With traditional AI, you ask it a question and it spits out an answer, but no one really knows how it makes its decisions. It’s a black box,” said Jon Donnelly, a PhD student in the department of computer science at Duke University, Durham, North Carolina, and first author on a new paper in Radiology describing the model.
“With our approach, people know how the algorithm comes up with its output so they can fact-check it and trust it,” he said.
One in eight women will develop invasive breast cancer, and 1 in 39 will die from it. Mammograms miss about 20% of breast cancers. (The shortcomings of genetic screening and mammograms received extra attention recently when actress Olivia Munn disclosed that she’d been treated for an aggressive form of breast cancer despite a normal mammogram and a negative genetic test.)
The model could help doctors bring the often-abstract idea of AI to the bedside in a meaningful way, said radiologist Vivianne Freitas, MD, assistant professor of medical imaging at the University of Toronto.
“This marks a new chapter in the field of AI,” said Dr. Freitas, who authored an editorial lauding the new paper. “It makes AI more tangible and understandable, thereby improving its potential for acceptance.”
AI as a Second Set of Eyes
Mr. Donnelly described AsymMirai as a simpler, more transparent, and easier-to-use version of Mirai, a breakthrough AI model which made headlines in 2021 with its promise to determine with unprecedented accuracy whether a patient is likely to get breast cancer within the next 5 years.
Mirai identified up to twice as many future cancer diagnoses as the conventional risk calculator Tyrer-Cuzick. It also maintained accuracy across a diverse set of patients — a notable plus for two fields (AI and healthcare) notorious for delivering poorer results for minorities.
Tyrer-Cuzick and other lower-tech risk calculators use personal and family history to statistically calculate risk. Mirai, on the other hand, analyzes countless bits of raw data embedded in a mammogram to decipher patterns a radiologist’s eyes may not catch. Four images, including two angles from each breast, are fed into the model, which produces a score between 0 and 1 to indicate the person’s risk of getting breast cancer in 1, 3, or 5 years.
But even Mirai’s creators have conceded they didn’t know exactly how it arrives at that score — a fact that has fueled hesitancy among clinicians.
Study coauthor Fides Schwartz, MD, a radiologist at Brigham and Women’s Hospital, Boston, said researchers were able to crack the code on Mirai’s “black box,” finding that its scores were largely determined by assessing subtle differences between right breast tissue and left breast tissue.
Knowing this, the research team simplified the model to predict risk based solely on “local bilateral dissimilarity.” AsymMirai was born.
The team then used AsymMirai to look back at > 200,000 mammograms from nearly 82,000 patients. They found it worked nearly as well as its predecessor, assigning a higher risk to those who would go on to develop cancer 66% of the time (vs Mirai’s 71%). In patients where it noticed the same asymmetry multiple years in a row it worked even better, with an 88% chance of giving people who would develop cancer later a higher score than those who would not.
“We found that we can, with surprisingly high accuracy, predict whether a woman will develop cancer in the next 1-5 years based solely on localized differences between her left and right breast tissue,” said Mr. Donnelly.
Dr. Schwartz imagines a day when radiologists could use the model to help develop personalized screening strategies for patients. Doctors might advise those with higher scores to get screened more often than guidelines suggest, supplement mammograms with an MRI , and keep a close watch on trouble spots identified by AI.
“For people with really low risk, on the other hand, maybe we can save them an annual exam that’s not super pleasant and might not be necessary,” said Dr. Schwartz.
Cautious Optimism
Robert Smith, PhD, senior vice president of early cancer detection science at the American Cancer Society, noted that AI has been used for decades to try to reduce radiologists’ workload and improve diagnoses.
“But AI just never really lived up to its fullest potential,” Dr. Smith said, “quite often because it was being used as a crutch by inexperienced radiologists who, instead of interpreting the mammogram and then seeing what AI had to say ended up letting AI do most of the work which, frankly, just wasn’t that accurate.”
He’s hopeful that newer, more sophisticated iterations of AI medical imaging platforms (roughly 18-20 models are in development) can ultimately save women’s lives, particularly in areas where radiologists are in short supply.
But he believes it will be a long time before doctors, or their patients, are willing to risk postponing a mammogram based on an algorithm.
A version of this article appeared on Medscape.com.
A new way of using artificial intelligence (AI) can predict breast cancer 5 years in advance with impressive accuracy — and unlike previous AI models, we know how this one works.
The new AI system, called AsymMirai, simplifies previous models by solely comparing differences between right and left breasts to predict risk. It could potentially save lives, prevent unnecessary testing, and save the healthcare system money, its creators say.
“With traditional AI, you ask it a question and it spits out an answer, but no one really knows how it makes its decisions. It’s a black box,” said Jon Donnelly, a PhD student in the department of computer science at Duke University, Durham, North Carolina, and first author on a new paper in Radiology describing the model.
“With our approach, people know how the algorithm comes up with its output so they can fact-check it and trust it,” he said.
One in eight women will develop invasive breast cancer, and 1 in 39 will die from it. Mammograms miss about 20% of breast cancers. (The shortcomings of genetic screening and mammograms received extra attention recently when actress Olivia Munn disclosed that she’d been treated for an aggressive form of breast cancer despite a normal mammogram and a negative genetic test.)
The model could help doctors bring the often-abstract idea of AI to the bedside in a meaningful way, said radiologist Vivianne Freitas, MD, assistant professor of medical imaging at the University of Toronto.
“This marks a new chapter in the field of AI,” said Dr. Freitas, who authored an editorial lauding the new paper. “It makes AI more tangible and understandable, thereby improving its potential for acceptance.”
AI as a Second Set of Eyes
Mr. Donnelly described AsymMirai as a simpler, more transparent, and easier-to-use version of Mirai, a breakthrough AI model which made headlines in 2021 with its promise to determine with unprecedented accuracy whether a patient is likely to get breast cancer within the next 5 years.
Mirai identified up to twice as many future cancer diagnoses as the conventional risk calculator Tyrer-Cuzick. It also maintained accuracy across a diverse set of patients — a notable plus for two fields (AI and healthcare) notorious for delivering poorer results for minorities.
Tyrer-Cuzick and other lower-tech risk calculators use personal and family history to statistically calculate risk. Mirai, on the other hand, analyzes countless bits of raw data embedded in a mammogram to decipher patterns a radiologist’s eyes may not catch. Four images, including two angles from each breast, are fed into the model, which produces a score between 0 and 1 to indicate the person’s risk of getting breast cancer in 1, 3, or 5 years.
But even Mirai’s creators have conceded they didn’t know exactly how it arrives at that score — a fact that has fueled hesitancy among clinicians.
Study coauthor Fides Schwartz, MD, a radiologist at Brigham and Women’s Hospital, Boston, said researchers were able to crack the code on Mirai’s “black box,” finding that its scores were largely determined by assessing subtle differences between right breast tissue and left breast tissue.
Knowing this, the research team simplified the model to predict risk based solely on “local bilateral dissimilarity.” AsymMirai was born.
The team then used AsymMirai to look back at > 200,000 mammograms from nearly 82,000 patients. They found it worked nearly as well as its predecessor, assigning a higher risk to those who would go on to develop cancer 66% of the time (vs Mirai’s 71%). In patients where it noticed the same asymmetry multiple years in a row it worked even better, with an 88% chance of giving people who would develop cancer later a higher score than those who would not.
“We found that we can, with surprisingly high accuracy, predict whether a woman will develop cancer in the next 1-5 years based solely on localized differences between her left and right breast tissue,” said Mr. Donnelly.
Dr. Schwartz imagines a day when radiologists could use the model to help develop personalized screening strategies for patients. Doctors might advise those with higher scores to get screened more often than guidelines suggest, supplement mammograms with an MRI , and keep a close watch on trouble spots identified by AI.
“For people with really low risk, on the other hand, maybe we can save them an annual exam that’s not super pleasant and might not be necessary,” said Dr. Schwartz.
Cautious Optimism
Robert Smith, PhD, senior vice president of early cancer detection science at the American Cancer Society, noted that AI has been used for decades to try to reduce radiologists’ workload and improve diagnoses.
“But AI just never really lived up to its fullest potential,” Dr. Smith said, “quite often because it was being used as a crutch by inexperienced radiologists who, instead of interpreting the mammogram and then seeing what AI had to say ended up letting AI do most of the work which, frankly, just wasn’t that accurate.”
He’s hopeful that newer, more sophisticated iterations of AI medical imaging platforms (roughly 18-20 models are in development) can ultimately save women’s lives, particularly in areas where radiologists are in short supply.
But he believes it will be a long time before doctors, or their patients, are willing to risk postponing a mammogram based on an algorithm.
A version of this article appeared on Medscape.com.
Most Cancer Trial Centers Located Closer to White, Affluent Populations
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
FROM JAMA ONCOLOGY
New Drug Approvals Are the Wrong Metric for Cancer Policy
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
Extraordinary Patients Inspired Father of Cancer Immunotherapy
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.