Breast Cancer

Key clinical point: Switch to fulvestrant + palbociclib from aromatase inhibitor (AI) + palbociclib improved progression-free survival (PFS) without increasing toxicity in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) and high levels of ESR1 mutation in the blood (bESR1^mut).

Major finding: Median PFS improved significantly in the fulvestrant + palbociclib vs AI + palbociclib group (stratified hazard ratio 0.61; 2-sided P = .0040). The rates of most common grade ≥3 adverse events, such as neutropenia (44.3% and 41.7%, respectively) and lymphopenia (4.5% and 3.6%, respectively), were similar in the fulvestrant + palbociclib and AI + palbociclib groups.

Study details: Findings are from the phase 3, PADA-1 trial including 172 patients with ER+HER2− advanced BC, rising bESR1^mut, and no synchronous disease progression with first-line AI + palbociclib who were randomly assigned to continue AI + palbociclib or switch to fulvestrant + palbociclib.

Disclosures: This study was funded by Pfizer. Some authors declared receiving grants, honoraria, consulting fees, or travel support, or having other ties with several sources, including Pfizer.

Source: Bidard FC et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022 (Sep 29). Doi: 10.1016/S1470-2045(22)00555-1

Key clinical point: Switch to fulvestrant + palbociclib from aromatase inhibitor (AI) + palbociclib improved progression-free survival (PFS) without increasing toxicity in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) and high levels of ESR1 mutation in the blood (bESR1^mut).

Major finding: Median PFS improved significantly in the fulvestrant + palbociclib vs AI + palbociclib group (stratified hazard ratio 0.61; 2-sided P = .0040). The rates of most common grade ≥3 adverse events, such as neutropenia (44.3% and 41.7%, respectively) and lymphopenia (4.5% and 3.6%, respectively), were similar in the fulvestrant + palbociclib and AI + palbociclib groups.

Study details: Findings are from the phase 3, PADA-1 trial including 172 patients with ER+HER2− advanced BC, rising bESR1^mut, and no synchronous disease progression with first-line AI + palbociclib who were randomly assigned to continue AI + palbociclib or switch to fulvestrant + palbociclib.

Disclosures: This study was funded by Pfizer. Some authors declared receiving grants, honoraria, consulting fees, or travel support, or having other ties with several sources, including Pfizer.

Source: Bidard FC et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022 (Sep 29). Doi: 10.1016/S1470-2045(22)00555-1

Key clinical point: Switch to fulvestrant + palbociclib from aromatase inhibitor (AI) + palbociclib improved progression-free survival (PFS) without increasing toxicity in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) and high levels of ESR1 mutation in the blood (bESR1^mut).

Major finding: Median PFS improved significantly in the fulvestrant + palbociclib vs AI + palbociclib group (stratified hazard ratio 0.61; 2-sided P = .0040). The rates of most common grade ≥3 adverse events, such as neutropenia (44.3% and 41.7%, respectively) and lymphopenia (4.5% and 3.6%, respectively), were similar in the fulvestrant + palbociclib and AI + palbociclib groups.

Study details: Findings are from the phase 3, PADA-1 trial including 172 patients with ER+HER2− advanced BC, rising bESR1^mut, and no synchronous disease progression with first-line AI + palbociclib who were randomly assigned to continue AI + palbociclib or switch to fulvestrant + palbociclib.

Disclosures: This study was funded by Pfizer. Some authors declared receiving grants, honoraria, consulting fees, or travel support, or having other ties with several sources, including Pfizer.

Source: Bidard FC et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022 (Sep 29). Doi: 10.1016/S1470-2045(22)00555-1

Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.

A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.

“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.

Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.

Among frequent users of hair straighteners – meaning those who used them more than four times a year – the researchers found that women were 2.55 times more likely to be diagnosed with uterine cancer than those who never used these products.

In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.

This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.

Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.

“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.

While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.

Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.

One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.

Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”

The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.

Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”

She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.

“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
 

Not ready to go curly

Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.

“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.

Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.

She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.

“Going forward, I will have this done once a year instead of twice a year,” she said.

Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.

“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”

In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”

The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.

The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.

“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.

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

Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.

A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.

“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.

Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.

Among frequent users of hair straighteners – meaning those who used them more than four times a year – the researchers found that women were 2.55 times more likely to be diagnosed with uterine cancer than those who never used these products.

In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.

This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.

Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.

“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.

While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.

Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.

One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.

Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”

The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.

Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”

She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.

“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
 

Not ready to go curly

Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.

“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.

Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.

She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.

“Going forward, I will have this done once a year instead of twice a year,” she said.

Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.

“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”

In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”

The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.

The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.

“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.

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

Clarissa Ghazi gets lye relaxers, which contain the chemical sodium hydroxide, applied to her hair two to three times a year.

A recent study that made headlines over a potential link between hair straighteners and uterine cancer is not going to make her stop.

“This study is not enough to cause me to say I’ll stay away from this because [the researchers] don’t prove that using relaxers causes cancer,” Ms. Ghazi said.

Indeed, primary care doctors are unlikely to address the increased risk of uterine cancer in women who frequently use hair straighteners that the study reported.

Among frequent users of hair straighteners – meaning those who used them more than four times a year – the researchers found that women were 2.55 times more likely to be diagnosed with uterine cancer than those who never used these products.

In the recently published paper on this research, the authors said that they found an 80% higher adjusted risk of uterine cancer among women who had ever “straightened,” “relaxed,” or used “hair pressing products” in the 12 months before enrolling in their study.

This finding is “real, but small,” says internist Douglas S. Paauw, MD, professor of medicine at the University of Washington in Seattle.

Dr. Paauw is among several primary care doctors interviewed for this story who expressed little concern about the implications of this research for their patients.

“Since we have hundreds of things we are supposed to discuss at our 20-minute clinic visits, this would not make the cut,” Dr. Paauw said.

While it’s good to be able to answer questions a patient might ask about this new research, the study does not prove anything, he said.

Alan Nelson, MD, an internist-endocrinologist and former special adviser to the CEO of the American College of Physicians, said while the study is well done, the number of actual cases of uterine cancer found was small.

One of the reasons he would not recommend discussing the study with patients is that the brands of hair products used to straighten hair in the study were not identified.

Alexandra White, PhD, lead author of the study, said participants were simply asked, “In the past 12 months, how frequently have you or someone else straightened or relaxed your hair, or used hair pressing products?”

The terms “straightened,” “relaxed,” and “hair pressing products” were not defined, and “some women may have interpreted the term ‘pressing products’ to mean nonchemical products” such as flat irons, Dr. White, head of the National Institute of Environmental Health Sciences’ Environment and Cancer Epidemiology group, said in an email.

Dermatologist Crystal Aguh, MD, associate professor of dermatology at Johns Hopkins University, Baltimore, tweeted the following advice in light of the new findings: “The overall risk of uterine cancer is quite low so it’s important to remember that. For now, if you want to change your routine, there’s no downside to decreasing your frequency of hair straightening to every 12 weeks or more, as that may lessen your risk.”

She also noted that “styles like relaxer, silk pressing, and keratin treatments should only be done by a professional, as this will decrease the likelihood of hair damage and scalp irritation.

“I also encourage women to look for hair products free of parabens and phthalates (which are generically listed as “fragrance”) on products to minimize exposure to hormone disrupting chemicals.”
 

Not ready to go curly

Ms. Ghazi said she decided to stop using keratin straighteners years ago after she learned they are made with several added ingredients. That includes the chemical formaldehyde, a known carcinogen, according to the American Cancer Society.

“People have been relaxing their hair for a very long time, and I feel more comfortable using [a relaxer] to straighten my hair than any of the others out there,” Ms. Ghazi said.

Janaki Ram, who has had her hair chemically straightened several times, said the findings have not made her worried that straightening will cause her to get uterine cancer specifically, but that they are a reminder that the chemicals in these products could harm her in some other way.

She said the new study findings, her knowledge of the damage straightening causes to hair, and the lengthy amount of time receiving a keratin treatment takes will lead her to reduce the frequency with which she gets her hair straightened.

“Going forward, I will have this done once a year instead of twice a year,” she said.

Dr. White, the author of the paper, said in an interview that the takeaway for consumers is that women who reported frequent use of hair straighteners/relaxers and pressing products were more than twice as likely to go on to develop uterine cancer compared to women who reported no use of these products in the previous year.

“However, uterine cancer is relatively rare, so these increases in risks are small,” she said. “Less frequent use of these products was not as strongly associated with risk, suggesting that decreasing use may be an option to reduce harmful exposure. Black women were the most frequent users of these products and therefore these findings are more relevant for Black women.”

In a statement, Dr. White noted, “We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%.”

The findings were based on the Sister Study, which enrolled women living in the United States, including Puerto Rico, between 2003 and 2009. Participants needed to have at least one sister who had been diagnosed with breast cancer, been breast cancer-free themselves, and aged 35-74 years. Women who reported a diagnosis of uterine cancer before enrollment, had an uncertain uterine cancer history, or had a hysterectomy were excluded from the study.

The researchers examined hair product usage and uterine cancer incidence during an 11-year period among 33 ,947 women. The analysis controlled for variables such as age, race, and risk factors. At baseline, participants were asked to complete a questionnaire on hair products use in the previous 12 months.

“One of the original aims of the study was to better understand the environmental and genetic causes of breast cancer, but we are also interested in studying ovarian cancer, uterine cancer, and many other cancers and chronic diseases,” Dr. White said.

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

A new study underscores the importance of COVID-19 and regular COVID-19 testing among adults with a recent cancer diagnosis.

The Indiana statewide study, conducted at the beginning of the pandemic, found that unvaccinated adults with cancer and SARS-CoV-2 infection were nearly seven times more likely to die from any cause than uninfected adults with cancer.

“This analysis provides additional empirical evidence on the magnitude of risk to patients with cancer whose immune systems are often weakened either by the disease or treatment,” the study team wrote.

The study was published online in JMIR Cancer.

Although evidence has consistently revealed similar findings, the risk of death among unvaccinated people with cancer and COVID-19 has not been nearly as high in previous studies, lead author Brian E. Dixon, PhD, MBA, with Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, said in a statement. Previous studies from China, for instance, reported a two- to threefold greater risk of all-cause mortality among unvaccinated adults with cancer and COVID-19.

A potential reason for this discrepancy, Dr. Dixon noted, is that earlier studies were “generally smaller and made calculations based on data from a single cancer center or health system.”

Another reason is testing for COVID-19 early in the pandemic was limited to symptomatic individuals who may have had more severe infections, possibly leading to an overestimate of the association between SARS-CoV-2 infection, cancer, and all-cause mortality.

In the current analysis, researchers used electronic health records linked to Indiana’s statewide SARS-CoV-2 testing database and state vital records to evaluate the association between SARS-CoV-2 infection and all-cause mortality among 41,924 adults newly diagnosed with cancer between Jan. 1, 2019, and Dec. 31, 2020.

Most people with cancer were White (78.4%) and about half were male. At the time of diagnosis, 17% had one comorbid condition and about 10% had two or more. Most patients had breast cancer (14%), prostate cancer (13%), or melanoma (13%).

During the study period, 2,894 patients (7%) tested positive for SARS-CoV-2.

In multivariate adjusted analysis, the risk of death among those newly diagnosed with cancer increased by 91% (adjusted hazard ratio, 1.91) during the first year of the pandemic before vaccines were available, compared with the year before (January 2019 to Jan. 14, 2020).

During the pandemic period, the risk of death was roughly threefold higher among adults 65 years old and older, compared with adults 18-44 years old (aHR, 3.35).

When looking at the time from a cancer diagnosis to SARS-CoV-2 infection, infection was associated with an almost sevenfold increase in all-cause mortality (aHR, 6.91). Adults 65 years old and older had an almost threefold increased risk of dying, compared with their younger peers (aHR, 2.74).

Dr. Dixon and colleagues also observed an increased risk of death in men with cancer and COVID, compared with women (aHR, 1.23) and those with at least two comorbid conditions versus none (aHR, 2.12). In addition, the risk of dying was 9% higher among Indiana’s rural population than urban dwellers.

Compared with other cancer types, individuals with lung cancer and other digestive cancers had the highest risk of death after SARS-CoV-2 infection (aHR, 1.45 and 1.80, respectively).

“Our findings highlight the increased risk of death for adult cancer patients who test positive for COVID and underscore the importance to cancer patients – including those in remission – of vaccinations, boosters, and regular COVID testing,” Dr. Dixon commented.

“Our results should encourage individuals diagnosed with cancer not only to take preventive action, but also to expeditiously seek out treatments available in the marketplace should they test positive for COVID,” he added.

Support for the study was provided by Indiana University Simon Cancer Center and the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

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

A new study underscores the importance of COVID-19 and regular COVID-19 testing among adults with a recent cancer diagnosis.

The Indiana statewide study, conducted at the beginning of the pandemic, found that unvaccinated adults with cancer and SARS-CoV-2 infection were nearly seven times more likely to die from any cause than uninfected adults with cancer.

“This analysis provides additional empirical evidence on the magnitude of risk to patients with cancer whose immune systems are often weakened either by the disease or treatment,” the study team wrote.

The study was published online in JMIR Cancer.

Although evidence has consistently revealed similar findings, the risk of death among unvaccinated people with cancer and COVID-19 has not been nearly as high in previous studies, lead author Brian E. Dixon, PhD, MBA, with Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, said in a statement. Previous studies from China, for instance, reported a two- to threefold greater risk of all-cause mortality among unvaccinated adults with cancer and COVID-19.

A potential reason for this discrepancy, Dr. Dixon noted, is that earlier studies were “generally smaller and made calculations based on data from a single cancer center or health system.”

Another reason is testing for COVID-19 early in the pandemic was limited to symptomatic individuals who may have had more severe infections, possibly leading to an overestimate of the association between SARS-CoV-2 infection, cancer, and all-cause mortality.

In the current analysis, researchers used electronic health records linked to Indiana’s statewide SARS-CoV-2 testing database and state vital records to evaluate the association between SARS-CoV-2 infection and all-cause mortality among 41,924 adults newly diagnosed with cancer between Jan. 1, 2019, and Dec. 31, 2020.

Most people with cancer were White (78.4%) and about half were male. At the time of diagnosis, 17% had one comorbid condition and about 10% had two or more. Most patients had breast cancer (14%), prostate cancer (13%), or melanoma (13%).

During the study period, 2,894 patients (7%) tested positive for SARS-CoV-2.

In multivariate adjusted analysis, the risk of death among those newly diagnosed with cancer increased by 91% (adjusted hazard ratio, 1.91) during the first year of the pandemic before vaccines were available, compared with the year before (January 2019 to Jan. 14, 2020).

During the pandemic period, the risk of death was roughly threefold higher among adults 65 years old and older, compared with adults 18-44 years old (aHR, 3.35).

When looking at the time from a cancer diagnosis to SARS-CoV-2 infection, infection was associated with an almost sevenfold increase in all-cause mortality (aHR, 6.91). Adults 65 years old and older had an almost threefold increased risk of dying, compared with their younger peers (aHR, 2.74).

Dr. Dixon and colleagues also observed an increased risk of death in men with cancer and COVID, compared with women (aHR, 1.23) and those with at least two comorbid conditions versus none (aHR, 2.12). In addition, the risk of dying was 9% higher among Indiana’s rural population than urban dwellers.

Compared with other cancer types, individuals with lung cancer and other digestive cancers had the highest risk of death after SARS-CoV-2 infection (aHR, 1.45 and 1.80, respectively).

“Our findings highlight the increased risk of death for adult cancer patients who test positive for COVID and underscore the importance to cancer patients – including those in remission – of vaccinations, boosters, and regular COVID testing,” Dr. Dixon commented.

“Our results should encourage individuals diagnosed with cancer not only to take preventive action, but also to expeditiously seek out treatments available in the marketplace should they test positive for COVID,” he added.

Support for the study was provided by Indiana University Simon Cancer Center and the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

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

A new study underscores the importance of COVID-19 and regular COVID-19 testing among adults with a recent cancer diagnosis.

The Indiana statewide study, conducted at the beginning of the pandemic, found that unvaccinated adults with cancer and SARS-CoV-2 infection were nearly seven times more likely to die from any cause than uninfected adults with cancer.

“This analysis provides additional empirical evidence on the magnitude of risk to patients with cancer whose immune systems are often weakened either by the disease or treatment,” the study team wrote.

The study was published online in JMIR Cancer.

Although evidence has consistently revealed similar findings, the risk of death among unvaccinated people with cancer and COVID-19 has not been nearly as high in previous studies, lead author Brian E. Dixon, PhD, MBA, with Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, said in a statement. Previous studies from China, for instance, reported a two- to threefold greater risk of all-cause mortality among unvaccinated adults with cancer and COVID-19.

A potential reason for this discrepancy, Dr. Dixon noted, is that earlier studies were “generally smaller and made calculations based on data from a single cancer center or health system.”

Another reason is testing for COVID-19 early in the pandemic was limited to symptomatic individuals who may have had more severe infections, possibly leading to an overestimate of the association between SARS-CoV-2 infection, cancer, and all-cause mortality.

In the current analysis, researchers used electronic health records linked to Indiana’s statewide SARS-CoV-2 testing database and state vital records to evaluate the association between SARS-CoV-2 infection and all-cause mortality among 41,924 adults newly diagnosed with cancer between Jan. 1, 2019, and Dec. 31, 2020.

Most people with cancer were White (78.4%) and about half were male. At the time of diagnosis, 17% had one comorbid condition and about 10% had two or more. Most patients had breast cancer (14%), prostate cancer (13%), or melanoma (13%).

During the study period, 2,894 patients (7%) tested positive for SARS-CoV-2.

In multivariate adjusted analysis, the risk of death among those newly diagnosed with cancer increased by 91% (adjusted hazard ratio, 1.91) during the first year of the pandemic before vaccines were available, compared with the year before (January 2019 to Jan. 14, 2020).

During the pandemic period, the risk of death was roughly threefold higher among adults 65 years old and older, compared with adults 18-44 years old (aHR, 3.35).

When looking at the time from a cancer diagnosis to SARS-CoV-2 infection, infection was associated with an almost sevenfold increase in all-cause mortality (aHR, 6.91). Adults 65 years old and older had an almost threefold increased risk of dying, compared with their younger peers (aHR, 2.74).

Dr. Dixon and colleagues also observed an increased risk of death in men with cancer and COVID, compared with women (aHR, 1.23) and those with at least two comorbid conditions versus none (aHR, 2.12). In addition, the risk of dying was 9% higher among Indiana’s rural population than urban dwellers.

Compared with other cancer types, individuals with lung cancer and other digestive cancers had the highest risk of death after SARS-CoV-2 infection (aHR, 1.45 and 1.80, respectively).

“Our findings highlight the increased risk of death for adult cancer patients who test positive for COVID and underscore the importance to cancer patients – including those in remission – of vaccinations, boosters, and regular COVID testing,” Dr. Dixon commented.

“Our results should encourage individuals diagnosed with cancer not only to take preventive action, but also to expeditiously seek out treatments available in the marketplace should they test positive for COVID,” he added.

Support for the study was provided by Indiana University Simon Cancer Center and the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

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

PARIS – What do doctors know about their patients’ sexual health? Not a lot. What about oncologists who treat women with breast cancer? Not much more. Yet sexual dysfunction has a significant impact on the quality of life of patients during and after cancer.

To determine the extent of sexual dysfunction among women with breast cancer, Maria Alice Franzoi, MD, an oncologist at Gustave Roussy Hospital, Villejuif, France, analyzed data concerning sexuality from the CANTO cohort study. She showed that sexual dysfunction often predates the cancer diagnosis and doesn’t improve but rather worsens in the following 2 years. She presented her results at the annual meeting of the European Society for Medical Oncology.
 

Present at diagnosis

Dr. Franzoi, whose research projects have focused on patient monitoring post cancer, drew her conclusions from the data provided by CANTO, a longitudinal, prospective cohort study that monitors women being treated for localized breast cancer. Study participants answered the EORTC-QLQ-BR23 quality-of-life questionnaire at the time of diagnosis (T0), 1 year after diagnosis (T1), and 2 years after diagnosis (T2). Four factors were employed to better define women’s sex-related problems: poor body image, poor sexual functioning (activity and desire), lack of sexual pleasure, and a complete lack of sexual activity.

The analysis focused on the responses of 7,895 patients in the CANTO cohort study on sexual activity; 4,523 of those patients answered questions about sexual pleasure. Female respondents who reported engaging in no sexual activity did not have to answer the questions in this second section.

“Seventy-five percent of patients reported at least one of the four concerns during the study,” noted Dr. Franzoi during her presentation. This finding highlights the fact that “sexual problems are already present at the time of diagnosis in a considerable number of patients,” she said. More than a third of participants complained of at least one of the four items.
 

Developments after diagnosis

The proportion of women who reported no arousal or poor sexual function remained stable at around 30% over time, meaning that the sexual problems were reported in similar numbers at T0, T1, and T2. “However, after cancer, more patients are worried about a lack of sexual pleasure (38.7% at T1 and 38.1% at T2, vs. 29.1% at T0) or report having a negative body image (57.8% at T1 and 52.5% at T2, vs. 32.1% at T0),” said Dr. Franzoi.

She identified the following three variables as being associated with sexual dysfunction 2 years after diagnosis: the existence of this problem at the time of diagnosis, the use of adjuvant hormone therapy, and severe depression or a very high stress level after the first year of treatment.
 

Inadequate specific treatment

“Sexual dysfunction is a major unmet need with a significant impact on quality of life,” said Maryam Lustberg, MD, an oncologist at Yale School of Medicine, New Haven, Conn., who was invited to discuss the results at the conference.

Dr. Franzoi observed that most participants with sexual dysfunction that had continued 2 years after diagnosis had not been referred to a doctor for this problem. “In terms of sexual function, it’s better at T2 than at T1, but only 41% of these women have been seen by a gynecologist, and only 15% have received specific treatment,” she reported, emphasizing the need to assess and treat these issues “proactively” at the time of diagnosis and during and after treatment.

“Now we need to work out what the best treatment approach is,” commented Dr. Lustberg. She said that cancers other than breast and gynecologic cancers should also be taken into consideration. She cited the Sexual Health Assessment in Women With Lung Cancer study, which recently revealed that after being diagnosed with lung cancer, female patients experienced a drop in sexual desire (31% vs. 15% before diagnosis) and an increase in vaginal discomfort or dryness (43% vs. 13% before diagnosis). This study, presented in August to the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer, also revealed that different parameters affect satisfaction in one’s sex life, including fatigue, sadness, relationship problems with a partner, and even breathing. Dr. Lustberg concluded from this study that a multidisciplinary approach is needed for cancer survivors.

Dr. Franzoi received research funding from Resilience Care. Dr. Lustberg has links with AstraZeneca, Pfizer, Novartis, Sanofi, and Lilly.

This article was translated from the Medscape French edition.

PARIS – What do doctors know about their patients’ sexual health? Not a lot. What about oncologists who treat women with breast cancer? Not much more. Yet sexual dysfunction has a significant impact on the quality of life of patients during and after cancer.

To determine the extent of sexual dysfunction among women with breast cancer, Maria Alice Franzoi, MD, an oncologist at Gustave Roussy Hospital, Villejuif, France, analyzed data concerning sexuality from the CANTO cohort study. She showed that sexual dysfunction often predates the cancer diagnosis and doesn’t improve but rather worsens in the following 2 years. She presented her results at the annual meeting of the European Society for Medical Oncology.
 

Present at diagnosis

Dr. Franzoi, whose research projects have focused on patient monitoring post cancer, drew her conclusions from the data provided by CANTO, a longitudinal, prospective cohort study that monitors women being treated for localized breast cancer. Study participants answered the EORTC-QLQ-BR23 quality-of-life questionnaire at the time of diagnosis (T0), 1 year after diagnosis (T1), and 2 years after diagnosis (T2). Four factors were employed to better define women’s sex-related problems: poor body image, poor sexual functioning (activity and desire), lack of sexual pleasure, and a complete lack of sexual activity.

The analysis focused on the responses of 7,895 patients in the CANTO cohort study on sexual activity; 4,523 of those patients answered questions about sexual pleasure. Female respondents who reported engaging in no sexual activity did not have to answer the questions in this second section.

“Seventy-five percent of patients reported at least one of the four concerns during the study,” noted Dr. Franzoi during her presentation. This finding highlights the fact that “sexual problems are already present at the time of diagnosis in a considerable number of patients,” she said. More than a third of participants complained of at least one of the four items.
 

Developments after diagnosis

The proportion of women who reported no arousal or poor sexual function remained stable at around 30% over time, meaning that the sexual problems were reported in similar numbers at T0, T1, and T2. “However, after cancer, more patients are worried about a lack of sexual pleasure (38.7% at T1 and 38.1% at T2, vs. 29.1% at T0) or report having a negative body image (57.8% at T1 and 52.5% at T2, vs. 32.1% at T0),” said Dr. Franzoi.

She identified the following three variables as being associated with sexual dysfunction 2 years after diagnosis: the existence of this problem at the time of diagnosis, the use of adjuvant hormone therapy, and severe depression or a very high stress level after the first year of treatment.
 

Inadequate specific treatment

“Sexual dysfunction is a major unmet need with a significant impact on quality of life,” said Maryam Lustberg, MD, an oncologist at Yale School of Medicine, New Haven, Conn., who was invited to discuss the results at the conference.

Dr. Franzoi observed that most participants with sexual dysfunction that had continued 2 years after diagnosis had not been referred to a doctor for this problem. “In terms of sexual function, it’s better at T2 than at T1, but only 41% of these women have been seen by a gynecologist, and only 15% have received specific treatment,” she reported, emphasizing the need to assess and treat these issues “proactively” at the time of diagnosis and during and after treatment.

“Now we need to work out what the best treatment approach is,” commented Dr. Lustberg. She said that cancers other than breast and gynecologic cancers should also be taken into consideration. She cited the Sexual Health Assessment in Women With Lung Cancer study, which recently revealed that after being diagnosed with lung cancer, female patients experienced a drop in sexual desire (31% vs. 15% before diagnosis) and an increase in vaginal discomfort or dryness (43% vs. 13% before diagnosis). This study, presented in August to the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer, also revealed that different parameters affect satisfaction in one’s sex life, including fatigue, sadness, relationship problems with a partner, and even breathing. Dr. Lustberg concluded from this study that a multidisciplinary approach is needed for cancer survivors.

Dr. Franzoi received research funding from Resilience Care. Dr. Lustberg has links with AstraZeneca, Pfizer, Novartis, Sanofi, and Lilly.

This article was translated from the Medscape French edition.

PARIS – What do doctors know about their patients’ sexual health? Not a lot. What about oncologists who treat women with breast cancer? Not much more. Yet sexual dysfunction has a significant impact on the quality of life of patients during and after cancer.

To determine the extent of sexual dysfunction among women with breast cancer, Maria Alice Franzoi, MD, an oncologist at Gustave Roussy Hospital, Villejuif, France, analyzed data concerning sexuality from the CANTO cohort study. She showed that sexual dysfunction often predates the cancer diagnosis and doesn’t improve but rather worsens in the following 2 years. She presented her results at the annual meeting of the European Society for Medical Oncology.
 

Present at diagnosis

Dr. Franzoi, whose research projects have focused on patient monitoring post cancer, drew her conclusions from the data provided by CANTO, a longitudinal, prospective cohort study that monitors women being treated for localized breast cancer. Study participants answered the EORTC-QLQ-BR23 quality-of-life questionnaire at the time of diagnosis (T0), 1 year after diagnosis (T1), and 2 years after diagnosis (T2). Four factors were employed to better define women’s sex-related problems: poor body image, poor sexual functioning (activity and desire), lack of sexual pleasure, and a complete lack of sexual activity.

The analysis focused on the responses of 7,895 patients in the CANTO cohort study on sexual activity; 4,523 of those patients answered questions about sexual pleasure. Female respondents who reported engaging in no sexual activity did not have to answer the questions in this second section.

“Seventy-five percent of patients reported at least one of the four concerns during the study,” noted Dr. Franzoi during her presentation. This finding highlights the fact that “sexual problems are already present at the time of diagnosis in a considerable number of patients,” she said. More than a third of participants complained of at least one of the four items.
 

Developments after diagnosis

The proportion of women who reported no arousal or poor sexual function remained stable at around 30% over time, meaning that the sexual problems were reported in similar numbers at T0, T1, and T2. “However, after cancer, more patients are worried about a lack of sexual pleasure (38.7% at T1 and 38.1% at T2, vs. 29.1% at T0) or report having a negative body image (57.8% at T1 and 52.5% at T2, vs. 32.1% at T0),” said Dr. Franzoi.

She identified the following three variables as being associated with sexual dysfunction 2 years after diagnosis: the existence of this problem at the time of diagnosis, the use of adjuvant hormone therapy, and severe depression or a very high stress level after the first year of treatment.
 

Inadequate specific treatment

“Sexual dysfunction is a major unmet need with a significant impact on quality of life,” said Maryam Lustberg, MD, an oncologist at Yale School of Medicine, New Haven, Conn., who was invited to discuss the results at the conference.

Dr. Franzoi observed that most participants with sexual dysfunction that had continued 2 years after diagnosis had not been referred to a doctor for this problem. “In terms of sexual function, it’s better at T2 than at T1, but only 41% of these women have been seen by a gynecologist, and only 15% have received specific treatment,” she reported, emphasizing the need to assess and treat these issues “proactively” at the time of diagnosis and during and after treatment.

“Now we need to work out what the best treatment approach is,” commented Dr. Lustberg. She said that cancers other than breast and gynecologic cancers should also be taken into consideration. She cited the Sexual Health Assessment in Women With Lung Cancer study, which recently revealed that after being diagnosed with lung cancer, female patients experienced a drop in sexual desire (31% vs. 15% before diagnosis) and an increase in vaginal discomfort or dryness (43% vs. 13% before diagnosis). This study, presented in August to the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer, also revealed that different parameters affect satisfaction in one’s sex life, including fatigue, sadness, relationship problems with a partner, and even breathing. Dr. Lustberg concluded from this study that a multidisciplinary approach is needed for cancer survivors.

Dr. Franzoi received research funding from Resilience Care. Dr. Lustberg has links with AstraZeneca, Pfizer, Novartis, Sanofi, and Lilly.

This article was translated from the Medscape French edition.

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

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

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

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

Early-onset cancer – often defined as cancers diagnosed in adults younger than age 50 years – is an emerging global epidemic, according to a recent review.

While the rising incidence of early-onset colorectal cancer (CRC) is a well-documented problem, the trend appears to extend far beyond CRC. The authors traced patterns of early-onset cancer diagnoses across 14 different cancer types, including breast, prostate, and thyroid, over the past 3 decades and found increases in many countries.

Among the 14 cancers explored, eight relate to the digestive system, which highlights the potential role diet and the oral and gut microbiome may play in cancer risk, the authors noted.

And many of the factors that appear to influence cancer risk – such as diet, exercise, sleep, and vaccination against HPV and other cancer-causing microorganisms – are modifiable.

“[Our] immediate goals should be to raise awareness of the early-onset cancer epidemic and reduce exposure to [these] risk factors,” authors Tomotaka Ugai, MD, PhD, and Shuji Ogino, MD, PhD, with Harvard School of Public Health, Boston, noted in a joint email.

The paper was published in Nature Reviews Clinical Oncology.

While the rise in cancer screenings has contributed to earlier detection of cancers, a genuine increase in the incidence of some early-onset cancers also appears to be happening.

In the current review, Dr. Ugai, Dr. Ogino, and colleagues reviewed the literature and mapped trends in the incidence of 14 cancer types among 20- to 49-year-old adults in 44 countries between 2002 and 2012.

The authors found that, since the 1990s, the incidence of early-onset cancers in the breast, colorectum, endometrium, esophagus, extrahepatic bile duct, gallbladder, head/neck, kidney, liver, bone marrow, pancreas, prostate, stomach, and thyroid, has increased around the world. Looking at the United States, for instance, the average annual percent changes for kidney cancer was 3.6% in women and 4.1% in men and for multiple myeloma was 2% in women and 3% in men for 2002 to 2012.

This overall trend could reflect increased exposures to risk factors in early life and young adulthood, although “specific effects of individual exposures remain largely unknown,” the authors acknowledged.

Since the mid-20th century, substantial changes have occurred in diet, sleep, smoking, obesity, type 2 diabetes, and environmental exposures – all of which may influence the gut microbiome or interact with our genes to increase the incidence of early-onset cancers, the authors explained. For instance, obesity, smoking, and alcohol are all established risk factors for pancreatic cancer and have been linked with early-onset disease risk as well.

“Cancer is a multifactorial disease, and we are aware of the importance of genetics as a risk factor and screening for early detection, but this paper importantly brings to light the importance of correctable lifestyle habits that may slow the rise of early onset cancers,” oncologist Marleen Meyers, MD, director of the survivorship program at NYU Langone Perlmutter Cancer Center, who wasn’t involved in the review, said in an interview.

Although modifiable factors such as diet and exercise may ease the burden of these cancers, such changes are often difficult to implement, Dr. Meyers added. In addition, understanding the impact that certain factors, such as alcohol, obesity, physical activity, and delayed reproduction play in cancer risk requires more research to tease out, but “there is enough reason at this point to address these risk factors for both personal and public health benefits,” Dr. Meyers said.

Support for this research was provided in part by the U.S. National Institutes of Health, Cancer Research UK, Prevent Cancer Foundation, Japan Society for the Promotion of Science, and the Mishima Kaiun Memorial Foundation. Dr. Ugai, Dr. Ogino, and Dr. Meyers have disclosed no relevant financial relationships.

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

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.

Notably, the authors found that using standard chemotherapy agents in specific sequences can help reduce overall costs and improve the value of care.

Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.

“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.

Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.

In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.

The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.

On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.

Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.

But the models did show considerable differences in costs.

The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.

For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.

For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.

Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”

In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.

“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.

The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.

Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.

As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.

The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.

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

While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.

Notably, the authors found that using standard chemotherapy agents in specific sequences can help reduce overall costs and improve the value of care.

Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.

“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.

Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.

In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.

The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.

On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.

Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.

But the models did show considerable differences in costs.

The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.

For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.

For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.

Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”

In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.

“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.

The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.

Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.

As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.

The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.

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

While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.

Notably, the authors found that using standard chemotherapy agents in specific sequences can help reduce overall costs and improve the value of care.

Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.

“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.

Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.

In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.

The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.

On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.

Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.

But the models did show considerable differences in costs.

The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.

For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.

For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.

Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”

In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.

“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.

The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.

Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.

As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.

The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.

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

The phase 3 NALA trial² demonstrated superior outcomes with the combination of neratinib plus capecitabine vs lapatinib plus capecitabine among patients with previously treated HER2+ metastatic breast cancer (hazard ratio 0.76; 1-year PFS 29% vs 15%). Findings from a single-center retrospective study including 72 patients with HER2+ advanced breast cancer who received either neratinib plus capecitabine or neratinib alone support efficacy and tolerability in the real-world setting (Cunningham et al). Among all patients, the median PFS was 5.9 months and median OS was 15.0 months; for those with brain metastases (n = 38), median PFS and median OS were 5.7 and 12.5 months, respectively. The gastrointestinal toxicity of neratinib can affect its clinical use, and a total of 64% of patients in this study reported diarrhea (10% reported grade 3) despite using antidiarrheal prophylaxis.

The treatment algorithm for HER2+ metastatic breast cancer has been evolving at a rapid pace, specifically for second-line and beyond. Neratinib remains a relevant therapy choice for these patients. The central nervous system activity of neratinib and other tyrosine kinase inhibitors, such as tucatinib, often make these the preferred treatment options for patients with brain metastases and stimulate the idea of prevention of brain metastases at an earlier time point.

Young women with breast cancer encounter unique challenges related to the stage of life during which they are diagnosed. It is essential to consider the effect of cancer treatment on fertility, including direct effects of chemotherapy and the duration of endocrine therapy (5-10 years) that can delay attempts at conceiving. Potential concerns surrounding fertility preservation (FP) include the theoretical risk of increased estradiol levels and treatment delay to allow these procedures to occur; however, various studies have supported the safety of FP.³

A prospective cohort study including 1257 women of reproductive age who were diagnosed with breast cancer and underwent FP treatment demonstrated similar disease-specific mortality in women who underwent hormonal FP (adjusted hazard ratio [aHR] 0.59; 95% CI 0.32-1.09), those who underwent nonhormonal FP (aHR 0.51, 95% CI 0.20-1.29), and women who did not pursue FP (Marklund et al). Furthermore, among 723 women with detailed information on relapse there was no significant difference in rate of relapse or death among those who underwent hormonal FP (aHR 0.81; 95% CI 0.49-1.37) vs those who underwent nonhormonal FP (aHR 0.75; 95% CI 0.35-1.62).

The growing body of evidence in this field highlights the importance of oncofertility awareness for both patients and providers. Young women diagnosed with breast cancer should be offered referrals to fertility specialists when interested and educated on the safety of these approaches as it relates to breast cancer outcomes.

A multicenter retrospective study compared the efficacy and safety of controlled ovarian hyperstimulation with letrozole (LetCOH) or without letrozole (cCOH) among 97 young women (≤ 40 years) diagnosed with early-stage breast cancer (Goldrat et al). The LetCOH group had lower peak estradiol levels (343 pg/mL vs 1009 pg/mL; P < .001) and higher oocyte maturation rates compared with the cCOH group, but a similar number of mature oocytes collected (P = .281). Disease recurrence occurred more frequently in the LetCOH group than in the cCOH group (17% vs 7.2%), and five patients in total had a distant recurrence (four undergoing LetCOH vs one undergoing cCOH).

The LetCOH group did have larger tumors and a higher number of HER2+ cancers. These findings suggest that a COH protocol using letrozole can yield FP outcomes similar to those of the conventional protocol while minimizing exposure to high levels of estradiol. Extended follow-up and future prospective studies will be essential to gain survival data and further define the roles of various FP procedures.

Additional References

1. Bardia A, Tolaney SM, Loirat D, et al. Sacituzumab govitecan (SG) versus treatment of physician's choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): final results from the phase 3 ASCENT study. J Clin Oncol. 2022;40(16 Suppl):107 Doi: 10.1200/JCO.2022.40.16_suppl.1071
2. Saura C, Oliveira M, Feng YH, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020;38:3138-3149. Doi: 10.1200/JCO.20.00147
3. Moravek MB, Confino R, Lawson AK, et al. Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation. Breast Cancer Res Treat. 2021;186:429-437. Doi: 10.1007/s10549-020-06031-4

The phase 3 NALA trial² demonstrated superior outcomes with the combination of neratinib plus capecitabine vs lapatinib plus capecitabine among patients with previously treated HER2+ metastatic breast cancer (hazard ratio 0.76; 1-year PFS 29% vs 15%). Findings from a single-center retrospective study including 72 patients with HER2+ advanced breast cancer who received either neratinib plus capecitabine or neratinib alone support efficacy and tolerability in the real-world setting (Cunningham et al). Among all patients, the median PFS was 5.9 months and median OS was 15.0 months; for those with brain metastases (n = 38), median PFS and median OS were 5.7 and 12.5 months, respectively. The gastrointestinal toxicity of neratinib can affect its clinical use, and a total of 64% of patients in this study reported diarrhea (10% reported grade 3) despite using antidiarrheal prophylaxis.

The treatment algorithm for HER2+ metastatic breast cancer has been evolving at a rapid pace, specifically for second-line and beyond. Neratinib remains a relevant therapy choice for these patients. The central nervous system activity of neratinib and other tyrosine kinase inhibitors, such as tucatinib, often make these the preferred treatment options for patients with brain metastases and stimulate the idea of prevention of brain metastases at an earlier time point.

Young women with breast cancer encounter unique challenges related to the stage of life during which they are diagnosed. It is essential to consider the effect of cancer treatment on fertility, including direct effects of chemotherapy and the duration of endocrine therapy (5-10 years) that can delay attempts at conceiving. Potential concerns surrounding fertility preservation (FP) include the theoretical risk of increased estradiol levels and treatment delay to allow these procedures to occur; however, various studies have supported the safety of FP.³

A prospective cohort study including 1257 women of reproductive age who were diagnosed with breast cancer and underwent FP treatment demonstrated similar disease-specific mortality in women who underwent hormonal FP (adjusted hazard ratio [aHR] 0.59; 95% CI 0.32-1.09), those who underwent nonhormonal FP (aHR 0.51, 95% CI 0.20-1.29), and women who did not pursue FP (Marklund et al). Furthermore, among 723 women with detailed information on relapse there was no significant difference in rate of relapse or death among those who underwent hormonal FP (aHR 0.81; 95% CI 0.49-1.37) vs those who underwent nonhormonal FP (aHR 0.75; 95% CI 0.35-1.62).

The growing body of evidence in this field highlights the importance of oncofertility awareness for both patients and providers. Young women diagnosed with breast cancer should be offered referrals to fertility specialists when interested and educated on the safety of these approaches as it relates to breast cancer outcomes.

A multicenter retrospective study compared the efficacy and safety of controlled ovarian hyperstimulation with letrozole (LetCOH) or without letrozole (cCOH) among 97 young women (≤ 40 years) diagnosed with early-stage breast cancer (Goldrat et al). The LetCOH group had lower peak estradiol levels (343 pg/mL vs 1009 pg/mL; P < .001) and higher oocyte maturation rates compared with the cCOH group, but a similar number of mature oocytes collected (P = .281). Disease recurrence occurred more frequently in the LetCOH group than in the cCOH group (17% vs 7.2%), and five patients in total had a distant recurrence (four undergoing LetCOH vs one undergoing cCOH).

The LetCOH group did have larger tumors and a higher number of HER2+ cancers. These findings suggest that a COH protocol using letrozole can yield FP outcomes similar to those of the conventional protocol while minimizing exposure to high levels of estradiol. Extended follow-up and future prospective studies will be essential to gain survival data and further define the roles of various FP procedures.

Additional References

1. Bardia A, Tolaney SM, Loirat D, et al. Sacituzumab govitecan (SG) versus treatment of physician's choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): final results from the phase 3 ASCENT study. J Clin Oncol. 2022;40(16 Suppl):107 Doi: 10.1200/JCO.2022.40.16_suppl.1071
2. Saura C, Oliveira M, Feng YH, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020;38:3138-3149. Doi: 10.1200/JCO.20.00147
3. Moravek MB, Confino R, Lawson AK, et al. Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation. Breast Cancer Res Treat. 2021;186:429-437. Doi: 10.1007/s10549-020-06031-4

The phase 3 NALA trial² demonstrated superior outcomes with the combination of neratinib plus capecitabine vs lapatinib plus capecitabine among patients with previously treated HER2+ metastatic breast cancer (hazard ratio 0.76; 1-year PFS 29% vs 15%). Findings from a single-center retrospective study including 72 patients with HER2+ advanced breast cancer who received either neratinib plus capecitabine or neratinib alone support efficacy and tolerability in the real-world setting (Cunningham et al). Among all patients, the median PFS was 5.9 months and median OS was 15.0 months; for those with brain metastases (n = 38), median PFS and median OS were 5.7 and 12.5 months, respectively. The gastrointestinal toxicity of neratinib can affect its clinical use, and a total of 64% of patients in this study reported diarrhea (10% reported grade 3) despite using antidiarrheal prophylaxis.

The treatment algorithm for HER2+ metastatic breast cancer has been evolving at a rapid pace, specifically for second-line and beyond. Neratinib remains a relevant therapy choice for these patients. The central nervous system activity of neratinib and other tyrosine kinase inhibitors, such as tucatinib, often make these the preferred treatment options for patients with brain metastases and stimulate the idea of prevention of brain metastases at an earlier time point.

Young women with breast cancer encounter unique challenges related to the stage of life during which they are diagnosed. It is essential to consider the effect of cancer treatment on fertility, including direct effects of chemotherapy and the duration of endocrine therapy (5-10 years) that can delay attempts at conceiving. Potential concerns surrounding fertility preservation (FP) include the theoretical risk of increased estradiol levels and treatment delay to allow these procedures to occur; however, various studies have supported the safety of FP.³

A prospective cohort study including 1257 women of reproductive age who were diagnosed with breast cancer and underwent FP treatment demonstrated similar disease-specific mortality in women who underwent hormonal FP (adjusted hazard ratio [aHR] 0.59; 95% CI 0.32-1.09), those who underwent nonhormonal FP (aHR 0.51, 95% CI 0.20-1.29), and women who did not pursue FP (Marklund et al). Furthermore, among 723 women with detailed information on relapse there was no significant difference in rate of relapse or death among those who underwent hormonal FP (aHR 0.81; 95% CI 0.49-1.37) vs those who underwent nonhormonal FP (aHR 0.75; 95% CI 0.35-1.62).

The growing body of evidence in this field highlights the importance of oncofertility awareness for both patients and providers. Young women diagnosed with breast cancer should be offered referrals to fertility specialists when interested and educated on the safety of these approaches as it relates to breast cancer outcomes.

A multicenter retrospective study compared the efficacy and safety of controlled ovarian hyperstimulation with letrozole (LetCOH) or without letrozole (cCOH) among 97 young women (≤ 40 years) diagnosed with early-stage breast cancer (Goldrat et al). The LetCOH group had lower peak estradiol levels (343 pg/mL vs 1009 pg/mL; P < .001) and higher oocyte maturation rates compared with the cCOH group, but a similar number of mature oocytes collected (P = .281). Disease recurrence occurred more frequently in the LetCOH group than in the cCOH group (17% vs 7.2%), and five patients in total had a distant recurrence (four undergoing LetCOH vs one undergoing cCOH).

The LetCOH group did have larger tumors and a higher number of HER2+ cancers. These findings suggest that a COH protocol using letrozole can yield FP outcomes similar to those of the conventional protocol while minimizing exposure to high levels of estradiol. Extended follow-up and future prospective studies will be essential to gain survival data and further define the roles of various FP procedures.

Additional References

1. Bardia A, Tolaney SM, Loirat D, et al. Sacituzumab govitecan (SG) versus treatment of physician's choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): final results from the phase 3 ASCENT study. J Clin Oncol. 2022;40(16 Suppl):107 Doi: 10.1200/JCO.2022.40.16_suppl.1071
2. Saura C, Oliveira M, Feng YH, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020;38:3138-3149. Doi: 10.1200/JCO.20.00147
3. Moravek MB, Confino R, Lawson AK, et al. Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation. Breast Cancer Res Treat. 2021;186:429-437. Doi: 10.1007/s10549-020-06031-4

The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.

But the clinical significance of many of the inherited mutations that can now be identified remains unclear, and experts are torn on when and how to deploy all the new tests available. Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.

A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.

But the clinical significance is murkier for many other genetic tests.

Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.

When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.

“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.

Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.

But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.

It can also confuse patients.

“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.

For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.

But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.

“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.

Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.

And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.

“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”

After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.

(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)

Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.

But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.

At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”

As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.

There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.

The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.

Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.

“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.

Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.

Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.

The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.

“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.

But the clinical significance of many of the inherited mutations that can now be identified remains unclear, and experts are torn on when and how to deploy all the new tests available. Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.

A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.

But the clinical significance is murkier for many other genetic tests.

Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.

When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.

“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.

Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.

But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.

It can also confuse patients.

“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.

For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.

But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.

“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.

Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.

And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.

“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”

After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.

(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)

Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.

But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.

At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”

As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.

There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.

The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.

Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.

“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.

Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.

Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.

The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.

“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.

But the clinical significance of many of the inherited mutations that can now be identified remains unclear, and experts are torn on when and how to deploy all the new tests available. Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.

A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.

But the clinical significance is murkier for many other genetic tests.

Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.

When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.

“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.

Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.

But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.

It can also confuse patients.

“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.

For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.

But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.

“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.

Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.

And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.

“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”

After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.

(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)

Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.

But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.

At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”

As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.

There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.

The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.

Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.

“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.

Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.

Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.

The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.

“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.