Heidi Splete

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

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.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

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.

Many women with cancer want advice for managing sexual function issues, and clinicians are tuning in, new studies suggest.

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.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Although tubal sterilization is common, especially among those with lower income and education levels, misunderstandings persist about the reversibility of the procedure, and previous studies suggest that many pregnant individuals are not making well-informed decisions, wrote Sonya Borrero, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Network Open, the researchers randomized 350 pregnant individuals with Medicaid insurance to usual care or usual care plus a web-based decision aid in English or Spanish called MyDecision/MiDecisión that included written, audio, and video information about tubal sterilization. The tool also included an interactive table comparing tubal sterilization to other contraceptive options, exercises to clarify patients’ values, knowledge checks, and a final summary report.

The two primary outcomes were knowledge of tubal sterilization based on a 10-question true/false test and decisional conflict about contraceptive choices using the low-literacy Decision Conflict Scale. The participants ranged in age from 21 to 45 years, with a mean age of 29.7 years. Participants were randomized prior to 24 weeks’ gestation, and those in the intervention group completed the intervention immediately using a personal device or a university device in the clinical setting. Further assessments occurred by phone during the third trimester and at 3 months postpartum.

Participants in the decision aid group showed significantly greater knowledge of tubal sterilization compared with controls, with a mean of 76.5% correct responses to the knowledge questions, vs. 55.6% in the control group (P < .001). Decisional conflict scores also were significantly lower in the intervention group compared with controls (mean 12.7 vs. 18.7, P = .002).

The most dramatic knowledge gap related to permanence of tubal sterilization; 90.1% of participants in the intervention group answered correctly that the procedure is not easily reversible, compared to 39.3% of the controls. Similarly, 86.6% of the intervention group responded correctly that the tubes do not “come untied” spontaneously, vs. 33.7% of controls (P < .001 for both).

The findings were limited by several factors including the focus only on pregnant Medicaid patients, the presentation of the decision tool only at a point early in pregnancy, which may have been too soon for some participants to consider tubal sterilization, and a lack of data on long-term satisfaction or regret about tubal sterilization decisions, the researchers noted.

However, the knowledge differences between the intervention and control groups remained significant at the third trimester assessment, they said.

More research is needed in other populations and using other time points, but the current study results suggest that use of the MyDecision/MiDecisión tool in a real-world clinical setting at the actual time of decision-making could improve knowledge and inform patients’ choices, the researchers concluded. Improved patient education also could inform policy decisions about the potential elimination of the 30-day waiting period for sterilization procedures, they said.

The study was supported by the National Institute on Minority Health and Health Disparities. The researchers had no financial conflicts to disclose.

Although tubal sterilization is common, especially among those with lower income and education levels, misunderstandings persist about the reversibility of the procedure, and previous studies suggest that many pregnant individuals are not making well-informed decisions, wrote Sonya Borrero, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Network Open, the researchers randomized 350 pregnant individuals with Medicaid insurance to usual care or usual care plus a web-based decision aid in English or Spanish called MyDecision/MiDecisión that included written, audio, and video information about tubal sterilization. The tool also included an interactive table comparing tubal sterilization to other contraceptive options, exercises to clarify patients’ values, knowledge checks, and a final summary report.

The two primary outcomes were knowledge of tubal sterilization based on a 10-question true/false test and decisional conflict about contraceptive choices using the low-literacy Decision Conflict Scale. The participants ranged in age from 21 to 45 years, with a mean age of 29.7 years. Participants were randomized prior to 24 weeks’ gestation, and those in the intervention group completed the intervention immediately using a personal device or a university device in the clinical setting. Further assessments occurred by phone during the third trimester and at 3 months postpartum.

Participants in the decision aid group showed significantly greater knowledge of tubal sterilization compared with controls, with a mean of 76.5% correct responses to the knowledge questions, vs. 55.6% in the control group (P < .001). Decisional conflict scores also were significantly lower in the intervention group compared with controls (mean 12.7 vs. 18.7, P = .002).

The most dramatic knowledge gap related to permanence of tubal sterilization; 90.1% of participants in the intervention group answered correctly that the procedure is not easily reversible, compared to 39.3% of the controls. Similarly, 86.6% of the intervention group responded correctly that the tubes do not “come untied” spontaneously, vs. 33.7% of controls (P < .001 for both).

The findings were limited by several factors including the focus only on pregnant Medicaid patients, the presentation of the decision tool only at a point early in pregnancy, which may have been too soon for some participants to consider tubal sterilization, and a lack of data on long-term satisfaction or regret about tubal sterilization decisions, the researchers noted.

However, the knowledge differences between the intervention and control groups remained significant at the third trimester assessment, they said.

More research is needed in other populations and using other time points, but the current study results suggest that use of the MyDecision/MiDecisión tool in a real-world clinical setting at the actual time of decision-making could improve knowledge and inform patients’ choices, the researchers concluded. Improved patient education also could inform policy decisions about the potential elimination of the 30-day waiting period for sterilization procedures, they said.

The study was supported by the National Institute on Minority Health and Health Disparities. The researchers had no financial conflicts to disclose.

Although tubal sterilization is common, especially among those with lower income and education levels, misunderstandings persist about the reversibility of the procedure, and previous studies suggest that many pregnant individuals are not making well-informed decisions, wrote Sonya Borrero, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Network Open, the researchers randomized 350 pregnant individuals with Medicaid insurance to usual care or usual care plus a web-based decision aid in English or Spanish called MyDecision/MiDecisión that included written, audio, and video information about tubal sterilization. The tool also included an interactive table comparing tubal sterilization to other contraceptive options, exercises to clarify patients’ values, knowledge checks, and a final summary report.

The two primary outcomes were knowledge of tubal sterilization based on a 10-question true/false test and decisional conflict about contraceptive choices using the low-literacy Decision Conflict Scale. The participants ranged in age from 21 to 45 years, with a mean age of 29.7 years. Participants were randomized prior to 24 weeks’ gestation, and those in the intervention group completed the intervention immediately using a personal device or a university device in the clinical setting. Further assessments occurred by phone during the third trimester and at 3 months postpartum.

Participants in the decision aid group showed significantly greater knowledge of tubal sterilization compared with controls, with a mean of 76.5% correct responses to the knowledge questions, vs. 55.6% in the control group (P < .001). Decisional conflict scores also were significantly lower in the intervention group compared with controls (mean 12.7 vs. 18.7, P = .002).

The most dramatic knowledge gap related to permanence of tubal sterilization; 90.1% of participants in the intervention group answered correctly that the procedure is not easily reversible, compared to 39.3% of the controls. Similarly, 86.6% of the intervention group responded correctly that the tubes do not “come untied” spontaneously, vs. 33.7% of controls (P < .001 for both).

The findings were limited by several factors including the focus only on pregnant Medicaid patients, the presentation of the decision tool only at a point early in pregnancy, which may have been too soon for some participants to consider tubal sterilization, and a lack of data on long-term satisfaction or regret about tubal sterilization decisions, the researchers noted.

However, the knowledge differences between the intervention and control groups remained significant at the third trimester assessment, they said.

More research is needed in other populations and using other time points, but the current study results suggest that use of the MyDecision/MiDecisión tool in a real-world clinical setting at the actual time of decision-making could improve knowledge and inform patients’ choices, the researchers concluded. Improved patient education also could inform policy decisions about the potential elimination of the 30-day waiting period for sterilization procedures, they said.

The study was supported by the National Institute on Minority Health and Health Disparities. The researchers had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

While the increased risk of cancer in patients with metabolic syndrome is well established by research, the authors of a new study delve deeper by examining metabolic syndrome trajectories.

The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.

The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.

However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
 

What We Know About Metabolic Syndrome and Cancer Risk

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.

“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.

Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
 

What New Study Adds to Related Research

Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m² in the low-stable group to approximately 28 kg/m² in the elevated-increasing group.

The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.

Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
 

Does Metabolic Syndrome Cause Cancer?

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.

More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.

“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.

“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
 

What Additional Research is Needed?

Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.

In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.

The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.

Adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer, according to a new study of more than 44,000 individuals.

The conditions that comprise metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, China, and colleagues.

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2019 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
 

What Does New Study Add to Other Research on Metabolic Syndrome and Cancer Risk?

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years. The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

 What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
 

What Is the Takeaway Message for Clinical Practice?

The results suggest that monitoring and managing metabolic syndrome could help reduce cancer risk, the researchers concluded. 

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, said in a press release accompanying the study.

More research is needed to assess the impact of these interventions on cancer risk, he noted. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he said in a statement.

The study was supported by the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer, according to a new study of more than 44,000 individuals.

The conditions that comprise metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, China, and colleagues.

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2019 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
 

What Does New Study Add to Other Research on Metabolic Syndrome and Cancer Risk?

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years. The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

 What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
 

What Is the Takeaway Message for Clinical Practice?

The results suggest that monitoring and managing metabolic syndrome could help reduce cancer risk, the researchers concluded. 

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, said in a press release accompanying the study.

More research is needed to assess the impact of these interventions on cancer risk, he noted. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he said in a statement.

The study was supported by the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer, according to a new study of more than 44,000 individuals.

The conditions that comprise metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, China, and colleagues.

A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.

More recently, a 2019 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.

However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
 

What Does New Study Add to Other Research on Metabolic Syndrome and Cancer Risk?

In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).

The average age of the participants was 49 years. The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.

Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.

The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
 

 What Are the Limitations of This Research?

The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.

Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
 

What Is the Takeaway Message for Clinical Practice?

The results suggest that monitoring and managing metabolic syndrome could help reduce cancer risk, the researchers concluded. 

“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, said in a press release accompanying the study.

More research is needed to assess the impact of these interventions on cancer risk, he noted. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he said in a statement.

The study was supported by the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Sulfites, present in foods, drinks, pharmaceuticals, and personal care products, have been named the “Allergen of the Year” for 2024 by the American Contact Dermatitis Society (ACDS).

Sulfites are currently not found in most screening patch test series, so may be missed as a relevant contact allergen, Donald V. Belsito, MD, emeritus professor in the Department of Dermatology at Columbia University, New York City, said in his presentation on the Allergen of the Year on March 7 at the annual meeting of the American Contact Dermatitis Society in San Diego. Sulfites, he noted, are distinct from sulfates, and the groups do not cross-react with each other.

FabrikaCr/iStock/Getty Images Plus

Sodium disulfite, an inorganic compound, belongs to a group of sulfiting agents, which contain the sulfite ion SO₃²⁻ and include ammonium sulfite, potassium sulfite, and sodium sulfite, Dr. Belsito said. Sulfites function as antioxidants and preservatives in a range of products including food and beverages, personal care products, and pharmaceuticals.

The type of sulfite allergy diagnosed by patch testing is type IV hypersensitivity or delayed-type hypersensitivity, where patients present with pruritic, red, scaling macules, papulovesicles, and patches, Dr. Belsito told this news organization. “It is not the type I, immediate hypersensitivity that causes hives and, in some cases, anaphylaxis,” he said. Sulfites also can cause these side effects, so correct labeling of food and beverages is important, he noted.

Some common nonoccupational sulfite sources include hair coloring and bleach products, hairspray, tanning lotions, makeup, sunscreens, and deodorants, Dr. Belsito said in his presentation. Medications including topical antifungals, topical corticosteroids, and nasal solutions can be culprits, as can water in swimming pools, he noted.

In occupational settings, sulfites may be present not only in food and drink products but also can be used in production of products, such as those used for sterilization during beer and wine fermentation, Dr. Belsito said. Other potential occupational sources of sulfite exposure include healthcare settings and textile, chemical, rubber, and pharmaceutical manufacturing.

High-sulfite food products (> 100 ppm) to be aware of include dried fruit (raisins and prunes are exceptions), bottled lemon or lime juice (but not frozen products), wine, molasses, grape juice (white, or white, pink, and red sparkling), and pickled cocktail onions, Dr. Belsito said.

“Like other contact allergens, the clinical presentation correlates with exposure,” he added. A study by the North American Contact Dermatitis Group (NACDG) found that 28.8% of patients positive for sulfite allergy on patch testing presented with facial dermatitis, which was not only related to cosmetics and medications used on the face but also from products, such as shampoo, used on the scalp that dripped onto the face. “The scalp is relatively resistant to the expression of contact allergy and may not be involved at all,” he said.

According to the NACDG study, the hands were the second most common site of dermatitis associated with sulfites (20.5%) followed by generalized distribution (13.6%). These sites are to be expected, given the sources of food and beverage, personal care products, and occupational materials, Dr. Belsito said.

“Eczematous dermatitis of the lips is also common in patients with ingested food sources of sulfites,” he said.

Systemic contact dermatitis to sulfites has been documented following oral, rectal, and parental exposure, Dr. Belsito told this news organization. “Systemic dermatitis may present as a scattered/generalized dermatitis, symmetrical drug-related intertriginous and flexural exanthema (also referred to as baboon syndrome), or erythroderma,” he said.
 

How to Spot Sulfite Allergies

The exclusion of sulfites from most patch test series means that sulfite allergy diagnoses are often missed, despite the wide range of potential exposures, Dr. Belsito said.

“Most cases of allergic contact dermatitis occur at the site of application of the allergen,” he noted. Depending on the location of the dermatitis, a detailed history of exposures that includes cosmetics and topical medications, work-related materials, and foods and beverages might suggest a sulfite allergy, he said.

Given the range of potential clinical presentations and the many and varied exposures to sulfites, Dr. Belsito’s best tip for clinicians is to routinely screen for them and evaluate the many avenues of exposure if a patch test is positive, he said.

For now, he said he does not think additional research is needed on sulfites as allergens; instead, sulfites, such as sodium metabisulfite/sodium disulfite, should be included in all clinicians’ baseline screening series, he said.

The Allergen of the Year was also recently announced in the journal Dermatitis. Authors Samuel F. Ekstein, MS, and Erin M. Warshaw, MD, from the Department of Dermatology, Park Nicollet Health Services, Minneapolis, Minnesota, noted that the ACDS hoped to raise awareness of sulfites as a “significant allergen” and called for their increased inclusion in screening patch test series.

Patients identified with sulfite allergies can find alternative products on the ACDS CAMP (Contact Allergen Management Program) website, Dr. Warshaw said in an interview.

She also highlighted some examples of sulfites as allergens in healthcare settings in particular. She described one patient who presented with dermatitis at the site of three previous hand orthopedic procedures.

“Although surgical cleansers were suspected, the patient reacted to sodium metabisulfite. Review of the operating room contactants confirmed sulfites as preservatives in an injectable anesthetic and antibiotic used for wound irrigation,” she said. Another patient who had been treated for recurrent otitis externa and seborrheic dermatitis was found to be allergic to sulfites in an otic antibiotic suspension as well as in a ketoconazole cream product, she added.

In the paper, Dr. Warshaw and Mr. Ekstein called for the addition of sulfites to the test series. Although the NACDG added sodium metabisulfite to the series in 2017, sulfites are not part of the American Contact Dermatitis Core Series, they wrote. Sodium metabisulfite, they said, was added to the European baseline standard series after review of the 2019-2020 patch test reactivity and clinical relevance data.

The ACDS meeting is held every year the day before the annual meeting of the American Academy of Dermatology.

Dr. Belsito and Dr. Warshaw had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Sulfites, present in foods, drinks, pharmaceuticals, and personal care products, have been named the “Allergen of the Year” for 2024 by the American Contact Dermatitis Society (ACDS).

Sulfites are currently not found in most screening patch test series, so may be missed as a relevant contact allergen, Donald V. Belsito, MD, emeritus professor in the Department of Dermatology at Columbia University, New York City, said in his presentation on the Allergen of the Year on March 7 at the annual meeting of the American Contact Dermatitis Society in San Diego. Sulfites, he noted, are distinct from sulfates, and the groups do not cross-react with each other.

FabrikaCr/iStock/Getty Images Plus

Sodium disulfite, an inorganic compound, belongs to a group of sulfiting agents, which contain the sulfite ion SO₃²⁻ and include ammonium sulfite, potassium sulfite, and sodium sulfite, Dr. Belsito said. Sulfites function as antioxidants and preservatives in a range of products including food and beverages, personal care products, and pharmaceuticals.

The type of sulfite allergy diagnosed by patch testing is type IV hypersensitivity or delayed-type hypersensitivity, where patients present with pruritic, red, scaling macules, papulovesicles, and patches, Dr. Belsito told this news organization. “It is not the type I, immediate hypersensitivity that causes hives and, in some cases, anaphylaxis,” he said. Sulfites also can cause these side effects, so correct labeling of food and beverages is important, he noted.

Some common nonoccupational sulfite sources include hair coloring and bleach products, hairspray, tanning lotions, makeup, sunscreens, and deodorants, Dr. Belsito said in his presentation. Medications including topical antifungals, topical corticosteroids, and nasal solutions can be culprits, as can water in swimming pools, he noted.

In occupational settings, sulfites may be present not only in food and drink products but also can be used in production of products, such as those used for sterilization during beer and wine fermentation, Dr. Belsito said. Other potential occupational sources of sulfite exposure include healthcare settings and textile, chemical, rubber, and pharmaceutical manufacturing.

High-sulfite food products (> 100 ppm) to be aware of include dried fruit (raisins and prunes are exceptions), bottled lemon or lime juice (but not frozen products), wine, molasses, grape juice (white, or white, pink, and red sparkling), and pickled cocktail onions, Dr. Belsito said.

“Like other contact allergens, the clinical presentation correlates with exposure,” he added. A study by the North American Contact Dermatitis Group (NACDG) found that 28.8% of patients positive for sulfite allergy on patch testing presented with facial dermatitis, which was not only related to cosmetics and medications used on the face but also from products, such as shampoo, used on the scalp that dripped onto the face. “The scalp is relatively resistant to the expression of contact allergy and may not be involved at all,” he said.

According to the NACDG study, the hands were the second most common site of dermatitis associated with sulfites (20.5%) followed by generalized distribution (13.6%). These sites are to be expected, given the sources of food and beverage, personal care products, and occupational materials, Dr. Belsito said.

“Eczematous dermatitis of the lips is also common in patients with ingested food sources of sulfites,” he said.

Systemic contact dermatitis to sulfites has been documented following oral, rectal, and parental exposure, Dr. Belsito told this news organization. “Systemic dermatitis may present as a scattered/generalized dermatitis, symmetrical drug-related intertriginous and flexural exanthema (also referred to as baboon syndrome), or erythroderma,” he said.
 

How to Spot Sulfite Allergies

The exclusion of sulfites from most patch test series means that sulfite allergy diagnoses are often missed, despite the wide range of potential exposures, Dr. Belsito said.

“Most cases of allergic contact dermatitis occur at the site of application of the allergen,” he noted. Depending on the location of the dermatitis, a detailed history of exposures that includes cosmetics and topical medications, work-related materials, and foods and beverages might suggest a sulfite allergy, he said.

Given the range of potential clinical presentations and the many and varied exposures to sulfites, Dr. Belsito’s best tip for clinicians is to routinely screen for them and evaluate the many avenues of exposure if a patch test is positive, he said.

For now, he said he does not think additional research is needed on sulfites as allergens; instead, sulfites, such as sodium metabisulfite/sodium disulfite, should be included in all clinicians’ baseline screening series, he said.

The Allergen of the Year was also recently announced in the journal Dermatitis. Authors Samuel F. Ekstein, MS, and Erin M. Warshaw, MD, from the Department of Dermatology, Park Nicollet Health Services, Minneapolis, Minnesota, noted that the ACDS hoped to raise awareness of sulfites as a “significant allergen” and called for their increased inclusion in screening patch test series.

Patients identified with sulfite allergies can find alternative products on the ACDS CAMP (Contact Allergen Management Program) website, Dr. Warshaw said in an interview.

She also highlighted some examples of sulfites as allergens in healthcare settings in particular. She described one patient who presented with dermatitis at the site of three previous hand orthopedic procedures.

“Although surgical cleansers were suspected, the patient reacted to sodium metabisulfite. Review of the operating room contactants confirmed sulfites as preservatives in an injectable anesthetic and antibiotic used for wound irrigation,” she said. Another patient who had been treated for recurrent otitis externa and seborrheic dermatitis was found to be allergic to sulfites in an otic antibiotic suspension as well as in a ketoconazole cream product, she added.

In the paper, Dr. Warshaw and Mr. Ekstein called for the addition of sulfites to the test series. Although the NACDG added sodium metabisulfite to the series in 2017, sulfites are not part of the American Contact Dermatitis Core Series, they wrote. Sodium metabisulfite, they said, was added to the European baseline standard series after review of the 2019-2020 patch test reactivity and clinical relevance data.

The ACDS meeting is held every year the day before the annual meeting of the American Academy of Dermatology.

Dr. Belsito and Dr. Warshaw had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Sulfites, present in foods, drinks, pharmaceuticals, and personal care products, have been named the “Allergen of the Year” for 2024 by the American Contact Dermatitis Society (ACDS).

Sulfites are currently not found in most screening patch test series, so may be missed as a relevant contact allergen, Donald V. Belsito, MD, emeritus professor in the Department of Dermatology at Columbia University, New York City, said in his presentation on the Allergen of the Year on March 7 at the annual meeting of the American Contact Dermatitis Society in San Diego. Sulfites, he noted, are distinct from sulfates, and the groups do not cross-react with each other.

FabrikaCr/iStock/Getty Images Plus

Sodium disulfite, an inorganic compound, belongs to a group of sulfiting agents, which contain the sulfite ion SO₃²⁻ and include ammonium sulfite, potassium sulfite, and sodium sulfite, Dr. Belsito said. Sulfites function as antioxidants and preservatives in a range of products including food and beverages, personal care products, and pharmaceuticals.

The type of sulfite allergy diagnosed by patch testing is type IV hypersensitivity or delayed-type hypersensitivity, where patients present with pruritic, red, scaling macules, papulovesicles, and patches, Dr. Belsito told this news organization. “It is not the type I, immediate hypersensitivity that causes hives and, in some cases, anaphylaxis,” he said. Sulfites also can cause these side effects, so correct labeling of food and beverages is important, he noted.

Some common nonoccupational sulfite sources include hair coloring and bleach products, hairspray, tanning lotions, makeup, sunscreens, and deodorants, Dr. Belsito said in his presentation. Medications including topical antifungals, topical corticosteroids, and nasal solutions can be culprits, as can water in swimming pools, he noted.

In occupational settings, sulfites may be present not only in food and drink products but also can be used in production of products, such as those used for sterilization during beer and wine fermentation, Dr. Belsito said. Other potential occupational sources of sulfite exposure include healthcare settings and textile, chemical, rubber, and pharmaceutical manufacturing.

High-sulfite food products (> 100 ppm) to be aware of include dried fruit (raisins and prunes are exceptions), bottled lemon or lime juice (but not frozen products), wine, molasses, grape juice (white, or white, pink, and red sparkling), and pickled cocktail onions, Dr. Belsito said.

“Like other contact allergens, the clinical presentation correlates with exposure,” he added. A study by the North American Contact Dermatitis Group (NACDG) found that 28.8% of patients positive for sulfite allergy on patch testing presented with facial dermatitis, which was not only related to cosmetics and medications used on the face but also from products, such as shampoo, used on the scalp that dripped onto the face. “The scalp is relatively resistant to the expression of contact allergy and may not be involved at all,” he said.

According to the NACDG study, the hands were the second most common site of dermatitis associated with sulfites (20.5%) followed by generalized distribution (13.6%). These sites are to be expected, given the sources of food and beverage, personal care products, and occupational materials, Dr. Belsito said.

“Eczematous dermatitis of the lips is also common in patients with ingested food sources of sulfites,” he said.

Systemic contact dermatitis to sulfites has been documented following oral, rectal, and parental exposure, Dr. Belsito told this news organization. “Systemic dermatitis may present as a scattered/generalized dermatitis, symmetrical drug-related intertriginous and flexural exanthema (also referred to as baboon syndrome), or erythroderma,” he said.
 

How to Spot Sulfite Allergies

The exclusion of sulfites from most patch test series means that sulfite allergy diagnoses are often missed, despite the wide range of potential exposures, Dr. Belsito said.

“Most cases of allergic contact dermatitis occur at the site of application of the allergen,” he noted. Depending on the location of the dermatitis, a detailed history of exposures that includes cosmetics and topical medications, work-related materials, and foods and beverages might suggest a sulfite allergy, he said.

Given the range of potential clinical presentations and the many and varied exposures to sulfites, Dr. Belsito’s best tip for clinicians is to routinely screen for them and evaluate the many avenues of exposure if a patch test is positive, he said.

For now, he said he does not think additional research is needed on sulfites as allergens; instead, sulfites, such as sodium metabisulfite/sodium disulfite, should be included in all clinicians’ baseline screening series, he said.

The Allergen of the Year was also recently announced in the journal Dermatitis. Authors Samuel F. Ekstein, MS, and Erin M. Warshaw, MD, from the Department of Dermatology, Park Nicollet Health Services, Minneapolis, Minnesota, noted that the ACDS hoped to raise awareness of sulfites as a “significant allergen” and called for their increased inclusion in screening patch test series.

Patients identified with sulfite allergies can find alternative products on the ACDS CAMP (Contact Allergen Management Program) website, Dr. Warshaw said in an interview.

She also highlighted some examples of sulfites as allergens in healthcare settings in particular. She described one patient who presented with dermatitis at the site of three previous hand orthopedic procedures.

“Although surgical cleansers were suspected, the patient reacted to sodium metabisulfite. Review of the operating room contactants confirmed sulfites as preservatives in an injectable anesthetic and antibiotic used for wound irrigation,” she said. Another patient who had been treated for recurrent otitis externa and seborrheic dermatitis was found to be allergic to sulfites in an otic antibiotic suspension as well as in a ketoconazole cream product, she added.

In the paper, Dr. Warshaw and Mr. Ekstein called for the addition of sulfites to the test series. Although the NACDG added sodium metabisulfite to the series in 2017, sulfites are not part of the American Contact Dermatitis Core Series, they wrote. Sodium metabisulfite, they said, was added to the European baseline standard series after review of the 2019-2020 patch test reactivity and clinical relevance data.

The ACDS meeting is held every year the day before the annual meeting of the American Academy of Dermatology.

Dr. Belsito and Dr. Warshaw had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Clinicians are navigating how to begin treating their patients with lifileucel (Amtagvi, Iovance Biotherapeutics Inc.), a new treatment for melanoma with a hefty price tag.

The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.

Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
 

Insurance Adjustments

The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.

Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.

Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.

The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.

Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.

At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.

Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.

Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.

 

Logistics and Infrastructure

A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.

The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
 

Docs Hope TIL Improves in Several Ways

Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.

More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”

Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.

“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.

“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.

“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”

“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.  

In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.

The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.

The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.

Clinicians are navigating how to begin treating their patients with lifileucel (Amtagvi, Iovance Biotherapeutics Inc.), a new treatment for melanoma with a hefty price tag.

The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.

Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
 

Insurance Adjustments

The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.

Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.

Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.

The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.

Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.

At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.

Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.

Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.

 

Logistics and Infrastructure

A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.

The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
 

Docs Hope TIL Improves in Several Ways

Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.

More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”

Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.

“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.

“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.

“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”

“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.  

In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.

The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.

The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.

Clinicians are navigating how to begin treating their patients with lifileucel (Amtagvi, Iovance Biotherapeutics Inc.), a new treatment for melanoma with a hefty price tag.

The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.

Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
 

Insurance Adjustments

The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.

Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.

Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.

The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.

Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.

At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.

Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.

Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.

 

Logistics and Infrastructure

A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.

The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
 

Docs Hope TIL Improves in Several Ways

Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.

More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”

Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.

“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.

“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.

“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”

“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.  

In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.

The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.

The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.

TOPLINE:

Women with daily exposure to spironolactone for dermatologic conditions showed no higher risk of developing breast or gynecologic cancer than that of unexposed women.

METHODOLOGY:

• Spironolactone, used off-label for several skin conditions in women, carries a warning about an increased tumor risk associated with high doses in rat models, and its antiandrogen properties have prompted hypotheses about a possible increased risk for breast or gynecologic cancers.
• The researchers reviewed data on 420 women with a history of spironolactone use for acne, hair loss, and hirsutism and 3272 women with no spironolactone use at the authors› institution. Their mean age ranged from 42 to 63 years; the majority were White, and 38% were non-White.
• Median spironolactone doses ranged from 25 mg to 225 mg; chart reviews included 5-year follow-up data from the first spironolactone exposure to allow time for tumor development.

TAKEAWAY:

• A total of 37 of the 420 women exposed to spironolactone developed any tumors, as did 546 of the 3272 with no spironolactone exposure.
• After the researchers controlled for age and race, women exposed to spironolactone were no more likely to develop a malignant tumor than a benign tumor, compared with unexposed women (odds ratio [OR], 0.48, P = .2).
• The risk for breast or uterine cancer was not significantly different in the spironolactone and non-spironolactone groups (OR, 0.95, P > .9).

IN PRACTICE:

“Women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow-up, but no more frequently than the general population,” but more studies are needed to evaluate risk over longer periods of time, the researchers wrote.

SOURCE:

The lead author of the study was Rachel C. Hill, BS, a student at Weill Cornell Medical College, New York City, and Shari R. Lipner, MD, PhD, of the department of dermatology at Weill Cornell Medical College, was the corresponding author. The study was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The findings were limited by the retrospective design, as well as the small number of spironolactone patients analyzed, the short follow-up period, the lack of information about spironolactone courses, and the inability to control for family history of malignancy.

DISCLOSURES:

The study was supported by the National Center for Advancing Translational Sciences and a grant from the Clinical and Translational Science Center at Weill Cornell Medical College awarded to Ms. Hill. None of the authors had relevant disclosures; Dr. Lipner disclosed serving as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with daily exposure to spironolactone for dermatologic conditions showed no higher risk of developing breast or gynecologic cancer than that of unexposed women.

METHODOLOGY:

• Spironolactone, used off-label for several skin conditions in women, carries a warning about an increased tumor risk associated with high doses in rat models, and its antiandrogen properties have prompted hypotheses about a possible increased risk for breast or gynecologic cancers.
• The researchers reviewed data on 420 women with a history of spironolactone use for acne, hair loss, and hirsutism and 3272 women with no spironolactone use at the authors› institution. Their mean age ranged from 42 to 63 years; the majority were White, and 38% were non-White.
• Median spironolactone doses ranged from 25 mg to 225 mg; chart reviews included 5-year follow-up data from the first spironolactone exposure to allow time for tumor development.

TAKEAWAY:

• A total of 37 of the 420 women exposed to spironolactone developed any tumors, as did 546 of the 3272 with no spironolactone exposure.
• After the researchers controlled for age and race, women exposed to spironolactone were no more likely to develop a malignant tumor than a benign tumor, compared with unexposed women (odds ratio [OR], 0.48, P = .2).
• The risk for breast or uterine cancer was not significantly different in the spironolactone and non-spironolactone groups (OR, 0.95, P > .9).

IN PRACTICE:

“Women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow-up, but no more frequently than the general population,” but more studies are needed to evaluate risk over longer periods of time, the researchers wrote.

SOURCE:

The lead author of the study was Rachel C. Hill, BS, a student at Weill Cornell Medical College, New York City, and Shari R. Lipner, MD, PhD, of the department of dermatology at Weill Cornell Medical College, was the corresponding author. The study was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The findings were limited by the retrospective design, as well as the small number of spironolactone patients analyzed, the short follow-up period, the lack of information about spironolactone courses, and the inability to control for family history of malignancy.

DISCLOSURES:

The study was supported by the National Center for Advancing Translational Sciences and a grant from the Clinical and Translational Science Center at Weill Cornell Medical College awarded to Ms. Hill. None of the authors had relevant disclosures; Dr. Lipner disclosed serving as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with daily exposure to spironolactone for dermatologic conditions showed no higher risk of developing breast or gynecologic cancer than that of unexposed women.

METHODOLOGY:

• Spironolactone, used off-label for several skin conditions in women, carries a warning about an increased tumor risk associated with high doses in rat models, and its antiandrogen properties have prompted hypotheses about a possible increased risk for breast or gynecologic cancers.
• The researchers reviewed data on 420 women with a history of spironolactone use for acne, hair loss, and hirsutism and 3272 women with no spironolactone use at the authors› institution. Their mean age ranged from 42 to 63 years; the majority were White, and 38% were non-White.
• Median spironolactone doses ranged from 25 mg to 225 mg; chart reviews included 5-year follow-up data from the first spironolactone exposure to allow time for tumor development.

TAKEAWAY:

• A total of 37 of the 420 women exposed to spironolactone developed any tumors, as did 546 of the 3272 with no spironolactone exposure.
• After the researchers controlled for age and race, women exposed to spironolactone were no more likely to develop a malignant tumor than a benign tumor, compared with unexposed women (odds ratio [OR], 0.48, P = .2).
• The risk for breast or uterine cancer was not significantly different in the spironolactone and non-spironolactone groups (OR, 0.95, P > .9).

IN PRACTICE:

“Women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow-up, but no more frequently than the general population,” but more studies are needed to evaluate risk over longer periods of time, the researchers wrote.

SOURCE:

The lead author of the study was Rachel C. Hill, BS, a student at Weill Cornell Medical College, New York City, and Shari R. Lipner, MD, PhD, of the department of dermatology at Weill Cornell Medical College, was the corresponding author. The study was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The findings were limited by the retrospective design, as well as the small number of spironolactone patients analyzed, the short follow-up period, the lack of information about spironolactone courses, and the inability to control for family history of malignancy.

DISCLOSURES:

The study was supported by the National Center for Advancing Translational Sciences and a grant from the Clinical and Translational Science Center at Weill Cornell Medical College awarded to Ms. Hill. None of the authors had relevant disclosures; Dr. Lipner disclosed serving as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

A version of this article appeared on Medscape.com.

Breast cancer-specific mortality risk in men with hormone receptor–positive breast cancer persists for at least 20 years, but patterns of breast cancer–specific mortality (BCSM) are distinct from those in women, a new study finds.

Previous studies in women with hormone receptor–positive (HR+) breast cancer have shown a risk of distant recurrence and death for at least 20 years after diagnosis, but data for men are limited, wrote Julieta Leone, MD, of the Dana Farber Cancer Institute, Boston, and colleagues.
 

What is Known About Hormone Receptor–Positive Breast Cancer Mortality in Men vs. Women?

Invasive breast cancer in men is rare and consequently understudied, the researchers wrote. Previous studies of BCSM in men with more than 5 years’ follow-up consist mainly of case series at single institutions, the researchers wrote in JAMA Oncology (2024 Feb 29. doi: 10.1001/jamaoncol.2023.7194).

“We believed it would be important to study this issue to help inform the management of men with breast cancer,” corresponding author, José P. Leone, MD, said in an interview.

In 2021, Dr. J.P. Leone and colleagues published a study in Breast Cancer Research and Treatment that examined the 20-year risk of BCSM in women that included more than 36,000 individuals who had survived for 5 years, with a median of 14 years’ follow-up.

In that study of women, the BCSM risk at 20 years was significantly higher for those with HR-negative tumors, but the risk was still elevated for both types. Patients with stage IIIC HR-positive disease had four times the risk of BCSM over 20 years and those with stage IIIC HR-negative disease had seven times the risk of BCSM over 20 years compared with the risk of death not related to breast cancer, the researchers wrote.

Another study of nearly 2,400 men with breast cancer (mainly HR+) by Dr. J.P. Leone and colleagues showed that cancer stage, tumor subtype, and race were associated with overall survival and breast cancer-specific survival.
 

What Does the New Study Add?

The current study included 2,836 men diagnosed with stage I to stage III HR+ breast cancer between 1990 and 2008, using data from the Surveillance, Epidemiology, and End Results (SEER) database.

“We found that in men with breast cancer, the risk of breast cancer mortality persists for at least 20 years and that [the risk] depends on traditional clinicopathologic factors, such as age, tumor size, nodal status and tumor grade,” Dr. J.P. Leone said in an interview.

“The prolonged risk [of breast-cancer specific mortality] over 20 years that we observed in our study is similar to that previously reported in women; however, the kinetics of the risk over the 20-year period appears different in men,” he emphasized.

The men in the study, especially those with a higher stage of disease, appeared to have a bimodal distribution of the BRCA mortality risk, he said.

Two peaks were identified, he explained; an early peak in mortality risk at approximately 4 years from diagnosis and another at approximately 11 years after diagnosis.

Although women with breast cancer had a prolonged risk of breast cancer mortality, “the kinetics of the risk does not include 2 peaks, even in women with higher stage of disease.” In women with higher stage breast cancer, the peak mortality risk occurs approximately 5 years after diagnosis, he said.

The reasons for the later peak in men remain unclear, the researchers wrote in the study, but possible explanations include nonadherence to endocrine therapy, differences in tumor biologic factors, and differences in the tumor microenvironment between men and women, they noted, in the discussion section.
 

What Drives the Risk?

Key factors for breast cancer-specific mortality were age, tumor stage, and tumor grade.

The cumulative 20-year risk of BCSM in the current study was 12.4%, 26.2%, and 46.0% for stage I, II, and III, respectively. The adjusted BCSM risk was increased in patients younger than 50 years, those with grade II or III/IV tumors, and those with stage II or III disease.
 

What Are the Limitations?

The current study by Leone and colleagues was limited by the relatively small subgroup sample of men with stage III and N3 disease, lack of data on the use of systemic therapies, and lack of data on human epidermal growth factor receptor 2 gene (ERBB2), the researchers wrote. However, the long-term follow-up strengthened the results, and the study is the first known to assess 20-year BCSM risk in men with nonmetastatic HR+ breast cancer.

What Do Oncologists Need to Know About the Study?

The study findings indicate that the risk of breast cancer mortality persists for 20 years in men with hormone receptor–positive breast cancer, Dr. J.P. Leone said in an interview. As in women, the risk depends on traditional clinicopathologic factors, he noted.

“However, the kinetics of that risk appears to be different between men and women. In order to reduce the breast cancer mortality risk in men with hormone receptor–positive breast cancer, it will be important for men to consider the benefits of the treatment options that may be indicated for their specific situation,” he said.

“I think early detection is also very important,” he emphasized. To that end, increased awareness of the possibility for breast cancer in men, as well as prompt intervention when breast cancer is suspected, will help to improve early detection when the risk of breast cancer mortality is lower, he added.
 

What Are the Next Steps for Research?

“I think our study underscores the need for additional research to improve our adjuvant therapy options in both men and women with hormone receptor-positive breast cancer, to reduce the risk of long-term mortality,” he said.

The study received no outside funding. Lead author Julieta Leone had no financial conflicts to disclose. Dr. José P. Leone disclosed receiving institutional grants from Kazia Therapeutics and Seagen unrelated to the current study.

Breast cancer-specific mortality risk in men with hormone receptor–positive breast cancer persists for at least 20 years, but patterns of breast cancer–specific mortality (BCSM) are distinct from those in women, a new study finds.

Previous studies in women with hormone receptor–positive (HR+) breast cancer have shown a risk of distant recurrence and death for at least 20 years after diagnosis, but data for men are limited, wrote Julieta Leone, MD, of the Dana Farber Cancer Institute, Boston, and colleagues.
 

What is Known About Hormone Receptor–Positive Breast Cancer Mortality in Men vs. Women?

Invasive breast cancer in men is rare and consequently understudied, the researchers wrote. Previous studies of BCSM in men with more than 5 years’ follow-up consist mainly of case series at single institutions, the researchers wrote in JAMA Oncology (2024 Feb 29. doi: 10.1001/jamaoncol.2023.7194).

“We believed it would be important to study this issue to help inform the management of men with breast cancer,” corresponding author, José P. Leone, MD, said in an interview.

In 2021, Dr. J.P. Leone and colleagues published a study in Breast Cancer Research and Treatment that examined the 20-year risk of BCSM in women that included more than 36,000 individuals who had survived for 5 years, with a median of 14 years’ follow-up.

In that study of women, the BCSM risk at 20 years was significantly higher for those with HR-negative tumors, but the risk was still elevated for both types. Patients with stage IIIC HR-positive disease had four times the risk of BCSM over 20 years and those with stage IIIC HR-negative disease had seven times the risk of BCSM over 20 years compared with the risk of death not related to breast cancer, the researchers wrote.

Another study of nearly 2,400 men with breast cancer (mainly HR+) by Dr. J.P. Leone and colleagues showed that cancer stage, tumor subtype, and race were associated with overall survival and breast cancer-specific survival.
 

What Does the New Study Add?

The current study included 2,836 men diagnosed with stage I to stage III HR+ breast cancer between 1990 and 2008, using data from the Surveillance, Epidemiology, and End Results (SEER) database.

“We found that in men with breast cancer, the risk of breast cancer mortality persists for at least 20 years and that [the risk] depends on traditional clinicopathologic factors, such as age, tumor size, nodal status and tumor grade,” Dr. J.P. Leone said in an interview.

“The prolonged risk [of breast-cancer specific mortality] over 20 years that we observed in our study is similar to that previously reported in women; however, the kinetics of the risk over the 20-year period appears different in men,” he emphasized.

The men in the study, especially those with a higher stage of disease, appeared to have a bimodal distribution of the BRCA mortality risk, he said.

Two peaks were identified, he explained; an early peak in mortality risk at approximately 4 years from diagnosis and another at approximately 11 years after diagnosis.

Although women with breast cancer had a prolonged risk of breast cancer mortality, “the kinetics of the risk does not include 2 peaks, even in women with higher stage of disease.” In women with higher stage breast cancer, the peak mortality risk occurs approximately 5 years after diagnosis, he said.

The reasons for the later peak in men remain unclear, the researchers wrote in the study, but possible explanations include nonadherence to endocrine therapy, differences in tumor biologic factors, and differences in the tumor microenvironment between men and women, they noted, in the discussion section.
 

What Drives the Risk?

Key factors for breast cancer-specific mortality were age, tumor stage, and tumor grade.

The cumulative 20-year risk of BCSM in the current study was 12.4%, 26.2%, and 46.0% for stage I, II, and III, respectively. The adjusted BCSM risk was increased in patients younger than 50 years, those with grade II or III/IV tumors, and those with stage II or III disease.
 

What Are the Limitations?

The current study by Leone and colleagues was limited by the relatively small subgroup sample of men with stage III and N3 disease, lack of data on the use of systemic therapies, and lack of data on human epidermal growth factor receptor 2 gene (ERBB2), the researchers wrote. However, the long-term follow-up strengthened the results, and the study is the first known to assess 20-year BCSM risk in men with nonmetastatic HR+ breast cancer.

What Do Oncologists Need to Know About the Study?

The study findings indicate that the risk of breast cancer mortality persists for 20 years in men with hormone receptor–positive breast cancer, Dr. J.P. Leone said in an interview. As in women, the risk depends on traditional clinicopathologic factors, he noted.

“However, the kinetics of that risk appears to be different between men and women. In order to reduce the breast cancer mortality risk in men with hormone receptor–positive breast cancer, it will be important for men to consider the benefits of the treatment options that may be indicated for their specific situation,” he said.

“I think early detection is also very important,” he emphasized. To that end, increased awareness of the possibility for breast cancer in men, as well as prompt intervention when breast cancer is suspected, will help to improve early detection when the risk of breast cancer mortality is lower, he added.
 

What Are the Next Steps for Research?

“I think our study underscores the need for additional research to improve our adjuvant therapy options in both men and women with hormone receptor-positive breast cancer, to reduce the risk of long-term mortality,” he said.

The study received no outside funding. Lead author Julieta Leone had no financial conflicts to disclose. Dr. José P. Leone disclosed receiving institutional grants from Kazia Therapeutics and Seagen unrelated to the current study.

Breast cancer-specific mortality risk in men with hormone receptor–positive breast cancer persists for at least 20 years, but patterns of breast cancer–specific mortality (BCSM) are distinct from those in women, a new study finds.

Previous studies in women with hormone receptor–positive (HR+) breast cancer have shown a risk of distant recurrence and death for at least 20 years after diagnosis, but data for men are limited, wrote Julieta Leone, MD, of the Dana Farber Cancer Institute, Boston, and colleagues.
 

What is Known About Hormone Receptor–Positive Breast Cancer Mortality in Men vs. Women?

Invasive breast cancer in men is rare and consequently understudied, the researchers wrote. Previous studies of BCSM in men with more than 5 years’ follow-up consist mainly of case series at single institutions, the researchers wrote in JAMA Oncology (2024 Feb 29. doi: 10.1001/jamaoncol.2023.7194).

“We believed it would be important to study this issue to help inform the management of men with breast cancer,” corresponding author, José P. Leone, MD, said in an interview.

In 2021, Dr. J.P. Leone and colleagues published a study in Breast Cancer Research and Treatment that examined the 20-year risk of BCSM in women that included more than 36,000 individuals who had survived for 5 years, with a median of 14 years’ follow-up.

In that study of women, the BCSM risk at 20 years was significantly higher for those with HR-negative tumors, but the risk was still elevated for both types. Patients with stage IIIC HR-positive disease had four times the risk of BCSM over 20 years and those with stage IIIC HR-negative disease had seven times the risk of BCSM over 20 years compared with the risk of death not related to breast cancer, the researchers wrote.

Another study of nearly 2,400 men with breast cancer (mainly HR+) by Dr. J.P. Leone and colleagues showed that cancer stage, tumor subtype, and race were associated with overall survival and breast cancer-specific survival.
 

What Does the New Study Add?

The current study included 2,836 men diagnosed with stage I to stage III HR+ breast cancer between 1990 and 2008, using data from the Surveillance, Epidemiology, and End Results (SEER) database.

“We found that in men with breast cancer, the risk of breast cancer mortality persists for at least 20 years and that [the risk] depends on traditional clinicopathologic factors, such as age, tumor size, nodal status and tumor grade,” Dr. J.P. Leone said in an interview.

“The prolonged risk [of breast-cancer specific mortality] over 20 years that we observed in our study is similar to that previously reported in women; however, the kinetics of the risk over the 20-year period appears different in men,” he emphasized.

The men in the study, especially those with a higher stage of disease, appeared to have a bimodal distribution of the BRCA mortality risk, he said.

Two peaks were identified, he explained; an early peak in mortality risk at approximately 4 years from diagnosis and another at approximately 11 years after diagnosis.

Although women with breast cancer had a prolonged risk of breast cancer mortality, “the kinetics of the risk does not include 2 peaks, even in women with higher stage of disease.” In women with higher stage breast cancer, the peak mortality risk occurs approximately 5 years after diagnosis, he said.

The reasons for the later peak in men remain unclear, the researchers wrote in the study, but possible explanations include nonadherence to endocrine therapy, differences in tumor biologic factors, and differences in the tumor microenvironment between men and women, they noted, in the discussion section.
 

What Drives the Risk?

Key factors for breast cancer-specific mortality were age, tumor stage, and tumor grade.

The cumulative 20-year risk of BCSM in the current study was 12.4%, 26.2%, and 46.0% for stage I, II, and III, respectively. The adjusted BCSM risk was increased in patients younger than 50 years, those with grade II or III/IV tumors, and those with stage II or III disease.
 

What Are the Limitations?

The current study by Leone and colleagues was limited by the relatively small subgroup sample of men with stage III and N3 disease, lack of data on the use of systemic therapies, and lack of data on human epidermal growth factor receptor 2 gene (ERBB2), the researchers wrote. However, the long-term follow-up strengthened the results, and the study is the first known to assess 20-year BCSM risk in men with nonmetastatic HR+ breast cancer.

What Do Oncologists Need to Know About the Study?

The study findings indicate that the risk of breast cancer mortality persists for 20 years in men with hormone receptor–positive breast cancer, Dr. J.P. Leone said in an interview. As in women, the risk depends on traditional clinicopathologic factors, he noted.

“However, the kinetics of that risk appears to be different between men and women. In order to reduce the breast cancer mortality risk in men with hormone receptor–positive breast cancer, it will be important for men to consider the benefits of the treatment options that may be indicated for their specific situation,” he said.

“I think early detection is also very important,” he emphasized. To that end, increased awareness of the possibility for breast cancer in men, as well as prompt intervention when breast cancer is suspected, will help to improve early detection when the risk of breast cancer mortality is lower, he added.
 

What Are the Next Steps for Research?

“I think our study underscores the need for additional research to improve our adjuvant therapy options in both men and women with hormone receptor-positive breast cancer, to reduce the risk of long-term mortality,” he said.

The study received no outside funding. Lead author Julieta Leone had no financial conflicts to disclose. Dr. José P. Leone disclosed receiving institutional grants from Kazia Therapeutics and Seagen unrelated to the current study.