Sharon Worcester

The incidence of lung cancer in never-smokers (LCINS) is increasing, and experts think climate change may be driving the uptick.

LCINS differs histologically and epidemiologically from smoking-related cancers, occurring almost always as adenocarcinomas and mostly affecting women and individuals of Asian ancestry, according to a study published in Nature Reviews Clinical Oncology in January 2024. Cases of LCINS are estimated to be the fifth most common cause of cancer-related deaths worldwide.

During a plenary session at the 2024 World Congress on Lung Cancer, experts addressed the known and suspected causes of LCINS, including fallout from climate change, vaping, cannabis use, and effects of airborne carcinogen exposures arising from military conflict. These potential culprits are varied and sometimes interrelated — and they underscore the need for continued emphasis on environmental hazards, the panelists agreed.

Focusing on climate change — and taking action at the individual level — is a good place to start, said Leticia M. Nogueira, PhD, scientific director of health services research in the Surveillance and Health Equity Science Department of the American Cancer Society.
 

Long-Term Exposure to Wildfires Linked to Increased Cancer Risk

Climate change is associated with climate-driven disasters such as more intense hurricanes and more frequent wildfires that can expose populations to environmental carcinogens, Nogueira explained.

Such weather events disrupt the care of patients with cancer and lead to poorer outcomes, according to her own research. They also contribute to the rising incidence of LCINS, she said.

In a population-based study published in The Lancet Planetary Health, long-term exposure to wildfires was associated with an increased risk for lung cancer and brain tumors. Individuals exposed to a wildfire within 50 km of their residential locations in the prior decade has a 4.9% relatively higher incidence of lung cancer and a 10% relatively higher incidence of brain tumors.

“These findings are relevant on a global scale given the anticipated effects of climate change on wildfire frequency and severity,” the authors concluded, noting the study limitations and the need for further research.
 

How Clinicians Can Help

Nogueira urged attendees to take action to help improve healthcare outcomes.

“Let’s not forget that the healthcare system is one of the most emission-intensive industries in the world. Emissions from the US healthcare system exceed emission from the entire UK, and we can be doing much better.

“There is something for each one of us here today to do: We can champion environmentally responsible efforts at our institutions, we can engage with disaster preparedness and response ... and we can document ongoing suffering to increase awareness and incentivize action,” she said.

In a commentary published in CA: A Cancer Journal for Clinicians, Nogueira and her colleagues further addressed the links between climate change and cancer and listed various sources of greenhouse gas emissions and proposed interventions, including those associated with the healthcare industry.

“If you look at this list and say ‘No way — there is no chance my institution will do any of that,’ let me ask you something: Are you allowed to smoke on campus? How do you think that happened? How do you think that started?” she said, invoking Archimedes’ famous quote, “Give me a lever long enough, and I shall move the world.”

“You most certainly have the power to make a difference,” Nogueira said. “So recognize where your points of influence are – move your lever, move the world.”
 

A version of this article appeared on Medscape.com.

The incidence of lung cancer in never-smokers (LCINS) is increasing, and experts think climate change may be driving the uptick.

LCINS differs histologically and epidemiologically from smoking-related cancers, occurring almost always as adenocarcinomas and mostly affecting women and individuals of Asian ancestry, according to a study published in Nature Reviews Clinical Oncology in January 2024. Cases of LCINS are estimated to be the fifth most common cause of cancer-related deaths worldwide.

During a plenary session at the 2024 World Congress on Lung Cancer, experts addressed the known and suspected causes of LCINS, including fallout from climate change, vaping, cannabis use, and effects of airborne carcinogen exposures arising from military conflict. These potential culprits are varied and sometimes interrelated — and they underscore the need for continued emphasis on environmental hazards, the panelists agreed.

Focusing on climate change — and taking action at the individual level — is a good place to start, said Leticia M. Nogueira, PhD, scientific director of health services research in the Surveillance and Health Equity Science Department of the American Cancer Society.
 

Long-Term Exposure to Wildfires Linked to Increased Cancer Risk

Climate change is associated with climate-driven disasters such as more intense hurricanes and more frequent wildfires that can expose populations to environmental carcinogens, Nogueira explained.

Such weather events disrupt the care of patients with cancer and lead to poorer outcomes, according to her own research. They also contribute to the rising incidence of LCINS, she said.

In a population-based study published in The Lancet Planetary Health, long-term exposure to wildfires was associated with an increased risk for lung cancer and brain tumors. Individuals exposed to a wildfire within 50 km of their residential locations in the prior decade has a 4.9% relatively higher incidence of lung cancer and a 10% relatively higher incidence of brain tumors.

“These findings are relevant on a global scale given the anticipated effects of climate change on wildfire frequency and severity,” the authors concluded, noting the study limitations and the need for further research.
 

How Clinicians Can Help

Nogueira urged attendees to take action to help improve healthcare outcomes.

“Let’s not forget that the healthcare system is one of the most emission-intensive industries in the world. Emissions from the US healthcare system exceed emission from the entire UK, and we can be doing much better.

“There is something for each one of us here today to do: We can champion environmentally responsible efforts at our institutions, we can engage with disaster preparedness and response ... and we can document ongoing suffering to increase awareness and incentivize action,” she said.

In a commentary published in CA: A Cancer Journal for Clinicians, Nogueira and her colleagues further addressed the links between climate change and cancer and listed various sources of greenhouse gas emissions and proposed interventions, including those associated with the healthcare industry.

“If you look at this list and say ‘No way — there is no chance my institution will do any of that,’ let me ask you something: Are you allowed to smoke on campus? How do you think that happened? How do you think that started?” she said, invoking Archimedes’ famous quote, “Give me a lever long enough, and I shall move the world.”

“You most certainly have the power to make a difference,” Nogueira said. “So recognize where your points of influence are – move your lever, move the world.”
 

A version of this article appeared on Medscape.com.

The incidence of lung cancer in never-smokers (LCINS) is increasing, and experts think climate change may be driving the uptick.

LCINS differs histologically and epidemiologically from smoking-related cancers, occurring almost always as adenocarcinomas and mostly affecting women and individuals of Asian ancestry, according to a study published in Nature Reviews Clinical Oncology in January 2024. Cases of LCINS are estimated to be the fifth most common cause of cancer-related deaths worldwide.

During a plenary session at the 2024 World Congress on Lung Cancer, experts addressed the known and suspected causes of LCINS, including fallout from climate change, vaping, cannabis use, and effects of airborne carcinogen exposures arising from military conflict. These potential culprits are varied and sometimes interrelated — and they underscore the need for continued emphasis on environmental hazards, the panelists agreed.

Focusing on climate change — and taking action at the individual level — is a good place to start, said Leticia M. Nogueira, PhD, scientific director of health services research in the Surveillance and Health Equity Science Department of the American Cancer Society.
 

Long-Term Exposure to Wildfires Linked to Increased Cancer Risk

Climate change is associated with climate-driven disasters such as more intense hurricanes and more frequent wildfires that can expose populations to environmental carcinogens, Nogueira explained.

Such weather events disrupt the care of patients with cancer and lead to poorer outcomes, according to her own research. They also contribute to the rising incidence of LCINS, she said.

In a population-based study published in The Lancet Planetary Health, long-term exposure to wildfires was associated with an increased risk for lung cancer and brain tumors. Individuals exposed to a wildfire within 50 km of their residential locations in the prior decade has a 4.9% relatively higher incidence of lung cancer and a 10% relatively higher incidence of brain tumors.

“These findings are relevant on a global scale given the anticipated effects of climate change on wildfire frequency and severity,” the authors concluded, noting the study limitations and the need for further research.
 

How Clinicians Can Help

Nogueira urged attendees to take action to help improve healthcare outcomes.

“Let’s not forget that the healthcare system is one of the most emission-intensive industries in the world. Emissions from the US healthcare system exceed emission from the entire UK, and we can be doing much better.

“There is something for each one of us here today to do: We can champion environmentally responsible efforts at our institutions, we can engage with disaster preparedness and response ... and we can document ongoing suffering to increase awareness and incentivize action,” she said.

In a commentary published in CA: A Cancer Journal for Clinicians, Nogueira and her colleagues further addressed the links between climate change and cancer and listed various sources of greenhouse gas emissions and proposed interventions, including those associated with the healthcare industry.

“If you look at this list and say ‘No way — there is no chance my institution will do any of that,’ let me ask you something: Are you allowed to smoke on campus? How do you think that happened? How do you think that started?” she said, invoking Archimedes’ famous quote, “Give me a lever long enough, and I shall move the world.”

“You most certainly have the power to make a difference,” Nogueira said. “So recognize where your points of influence are – move your lever, move the world.”
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

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

False-positive mammography results are common, but a large population-based cohort study conducted in Sweden found an elevated incidence of developing and dying of breast cancer up to 20 years after a false-positive result.

Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer, compared with those who did not have a false-positive result.

However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.

The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and “can be used to develop individualized risk-based breast cancer screening,” said the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm.

The findings were published online in JAMA Oncology.

About 11% of women in the United States and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer, compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.

To assess long-term outcomes after a false-positive result, the study investigators compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. 

Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio, 1.61).

Breast cancer risk was higher in older women – those aged 60-75 years (HR, 2.02) – vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).

After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) versus the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs. 1.47 for smaller tumors).

The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result versus no false-positive result; 95% CI, 0.89-1.25).

This study is the first to show that “women with a false-positive result are at increased risk of death from breast cancer,” Ms. Mao and colleagues concluded. This finding is “most probably associated with the increased breast cancer incidence,” given that the prognosis of patients with breast cancer was similar among those who had a false-positive result versus those who did not.

The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Ms. Mao and colleagues noted.

When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.

Overall, the findings indicate that clinicians “ should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, said in an interview.

Dr. Miglioretti, who has led research on false-positive mammography results and approaches to reduce false positives, noted that “this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future.”

The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Dr. Miglioretti said.

However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.

It is “important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results,” Dr. Miglioretti said.

This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Ms. Mao is supported by a grant from the China Scholarship Council. Dr. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.

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

False-positive mammography results are common, but a large population-based cohort study conducted in Sweden found an elevated incidence of developing and dying of breast cancer up to 20 years after a false-positive result.

Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer, compared with those who did not have a false-positive result.

However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.

The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and “can be used to develop individualized risk-based breast cancer screening,” said the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm.

The findings were published online in JAMA Oncology.

About 11% of women in the United States and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer, compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.

To assess long-term outcomes after a false-positive result, the study investigators compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. 

Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio, 1.61).

Breast cancer risk was higher in older women – those aged 60-75 years (HR, 2.02) – vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).

After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) versus the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs. 1.47 for smaller tumors).

The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result versus no false-positive result; 95% CI, 0.89-1.25).

This study is the first to show that “women with a false-positive result are at increased risk of death from breast cancer,” Ms. Mao and colleagues concluded. This finding is “most probably associated with the increased breast cancer incidence,” given that the prognosis of patients with breast cancer was similar among those who had a false-positive result versus those who did not.

The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Ms. Mao and colleagues noted.

When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.

Overall, the findings indicate that clinicians “ should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, said in an interview.

Dr. Miglioretti, who has led research on false-positive mammography results and approaches to reduce false positives, noted that “this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future.”

The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Dr. Miglioretti said.

However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.

It is “important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results,” Dr. Miglioretti said.

This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Ms. Mao is supported by a grant from the China Scholarship Council. Dr. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.

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

False-positive mammography results are common, but a large population-based cohort study conducted in Sweden found an elevated incidence of developing and dying of breast cancer up to 20 years after a false-positive result.

Women with a false-positive mammography result had 61% greater risk of developing breast cancer and an 84% greater risk of dying of breast cancer, compared with those who did not have a false-positive result.

However, the investigators also found that the risk for breast cancer varied by individual characteristics such as age and breast density.

The analysis provides clues about which patients with false-positive mammography results will go on to develop breast cancer and “can be used to develop individualized risk-based breast cancer screening,” said the investigators, led by Xinhe Mao, MSc, of Karolinska Institute, Stockholm.

The findings were published online in JAMA Oncology.

About 11% of women in the United States and 2.5% in Europe will receive a false-positive result after a single mammography screening, and previous research shows that these women have a higher risk of developing breast cancer, compared with women without false-positive results. Still, whether this risk for breast cancer varies by individual characteristics and whether an association between a false-positive mammography result and mortality exists remain unclear.

To assess long-term outcomes after a false-positive result, the study investigators compared 45,213 women who had a false-positive mammography result between 1991 and 2017 with 452,130 controls matched for age, calendar year of mammography, and screening history. These data came from the Stockholm Mammography Screening program and Swedish nationwide registers. The analysis also included 1,113 women with a false-positive result and 11,130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. 

Among women with a false-positive result, the 20-year cumulative breast cancer incidence was 11.3% compared with 7.3% among those without a false-positive (adjusted hazard ratio, 1.61).

Breast cancer risk was higher in older women – those aged 60-75 years (HR, 2.02) – vs younger women aged 40-49 years (HR, 1.38). Breast cancer risk was also higher among women with less dense breasts (HR, 4.65) vs more dense breasts (HR, 1.60) and those who underwent a biopsy during recall (HR, 1.77) vs those who did not (HR, 1.51).

After a false-positive result, cancers were more likely to occur on the ipsilateral side to the false-positive result (HR, 1.92) versus the contralateral (HR, 1.28) and were more common during the first 4 years of follow-up (HR, 2.57 in the first 2 years and 1.93 between 2 and 4 years). No statistical differences were observed based on tumor characteristics, aside from tumor size (HR, 1.78 for tumors ≥ 20 mm vs. 1.47 for smaller tumors).

The prognosis of patients with breast cancer did not differ on the basis of whether they had false-positive results before diagnosis (HR, 1.05 for a false-positive result versus no false-positive result; 95% CI, 0.89-1.25).

This study is the first to show that “women with a false-positive result are at increased risk of death from breast cancer,” Ms. Mao and colleagues concluded. This finding is “most probably associated with the increased breast cancer incidence,” given that the prognosis of patients with breast cancer was similar among those who had a false-positive result versus those who did not.

The authors noted that the increased risk for breast cancer after a false-positive result could suggest that false positives indicate the presence of small tumors that were missed or generally indicate a higher risk for breast cancer. Other factors, such as hormones or genetics, may be at play as well, but would need to be investigated in further studies, Ms. Mao and colleagues noted.

When individualizing surveillance after a false-positive result, age and breast density should be considered, the authors explained. Clinicians may also want to provide more intensive surveillance in the years after a false-positive result as well as education to patients about the risks associated with a false-positive result.

Overall, the findings indicate that clinicians “ should stress the importance of continued screening in women with false-positive results, given their higher risk of cancer, especially within the first 5 or so years after a false-positive result,” Diana L. Miglioretti, PhD, professor and division chief of biostatistics at the University of California, Davis, said in an interview.

Dr. Miglioretti, who has led research on false-positive mammography results and approaches to reduce false positives, noted that “this is a very important study confirming prior work by the Breast Cancer Surveillance Consortium showing individuals with false-positive screening mammography results are at increased risk of developing breast cancer in the future.”

The new evidence demonstrated an increased risk for death from breast cancer in patients who have a false-positive result is particularly worrisome because some studies suggest that women with false-positive results are less likely to return for screening, perhaps because of their negative experience, Dr. Miglioretti said.

However, her own research has shown that providing immediate screening mammography interpretation and same-day diagnostic workup to individuals who have not had a mammogram in the past 5 years and to younger women could prevent 40% of people from needing to return for diagnostic workup later and potentially reduce time to diagnosis for those with cancer.

It is “important that radiology facilities find ways to reduce false-positive results and the anxiety associated with these results,” Dr. Miglioretti said.

This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, and FORTE. Ms. Mao is supported by a grant from the China Scholarship Council. Dr. Miglioretti received funding from PCORI and NCI and royalties from Elsevier.

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

Adjuvant radiotherapy after radical prostatectomy provided no meaningful benefit in patients with prostate cancer but increased the risk for urinary and bowel morbidity, compared with men followed with observation alone, according to the latest results from the phase 3 RADICALS-RT trial.

The new findings showed no difference in the rate of 10-year freedom from distant metastases or overall survival in patients who received adjuvant radiotherapy vs. those who underwent observation with salvage radiotherapy if their disease progressed and provided further confirmation of earlier results reported in The Lancet in 2020.

Observation with early salvage radiotherapy in cases of biochemical failure should be the standard of care, concluded study coauthor Noel Clarke, MBBS, who presented the results at the annual meeting of the European Society for Medical Oncology.

Invited discussant and session cochair Shahneed Sandhu, MBBS, said that the findings definitively confirm the value of observation with salvage radiotherapy over adjuvant radiotherapy in this patient population.

“The approach of early salvage radiotherapy spared morbidity [from] radiation in the vast majority of patients, and further bowel and bladder toxicity is reduced in the setting of salvage radiotherapy,” said Dr. Sandhu, an associate professor and consultant medical oncologist at Peter MacCallum Cancer Centre, Victoria, Australia.

The aim of the RADICALS-RT study was to clarify the optimal timing for radiotherapy after radical prostatectomy in men with prostate cancer, which previously had been uncertain.

In the study, 697 patients were randomly assigned to adjuvant radiotherapy and 699 to observation with salvage radiotherapy. Participants had undergone radical prostatectomy; had a postoperative prostate-specific antigen (PSA) level ≤ 0.2 ng/mL; and at least one risk factor for cancer relapse, including pathologic T-stage III or IV, Gleason score of 7-10, positive margins, or preoperative PSA ≥ 10 ng/mL.

Patients in the observation arm received salvage radiotherapy if they experienced two consecutive PSA increases ≥ 0.1 ng/mL or three consecutive rises.

Overall, the investigators found similar rates of 10-year freedom from distant metastases in both arms: 93% in the adjuvant radiotherapy group vs. 90% in the observation group (hazard ratio, 0.68; P = .095). The 10-year overall survival rates were similar as well: 88% in the adjuvant radiotherapy group and 87% in the observation group (HR, 0.98; P = .92).

However, self-reported urinary and fecal incontinence rates at 1 year were significantly higher in the adjuvant radiotherapy group vs. the observation group, 60% of whom had not received salvage radiotherapy at that time.

Secondary outcome measures, including biochemical progression-free survival and time to further hormone therapy, were also similar in the treatment and observation arms.

Overall, the trial results “support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention, “ concluded Dr. Clarke, a professor and consultant urologist at the Christie Hospital and Salford Royal Hospital, Manchester, England.

And when biochemical recurrence does occur, Dr. Sandhu noted that prostate-specific membrane antigen PET is increasingly used in practice to help “define the extent of disease” and “tailor radiation fields.”

Dr. Clarke reported serving on advisory boards for Janssen, Astellas, and Bayer. Dr. Sandhu reported receiving research grant support and/or serving as a consultant or adviser for Advanced Accelerator Application (a Novartis company), AstraZeneca, Merck Sharp and Dohme, Roche/Genentech, Amgen, Pfizer, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, and Sehnwa.

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

Adjuvant radiotherapy after radical prostatectomy provided no meaningful benefit in patients with prostate cancer but increased the risk for urinary and bowel morbidity, compared with men followed with observation alone, according to the latest results from the phase 3 RADICALS-RT trial.

The new findings showed no difference in the rate of 10-year freedom from distant metastases or overall survival in patients who received adjuvant radiotherapy vs. those who underwent observation with salvage radiotherapy if their disease progressed and provided further confirmation of earlier results reported in The Lancet in 2020.

Observation with early salvage radiotherapy in cases of biochemical failure should be the standard of care, concluded study coauthor Noel Clarke, MBBS, who presented the results at the annual meeting of the European Society for Medical Oncology.

Invited discussant and session cochair Shahneed Sandhu, MBBS, said that the findings definitively confirm the value of observation with salvage radiotherapy over adjuvant radiotherapy in this patient population.

“The approach of early salvage radiotherapy spared morbidity [from] radiation in the vast majority of patients, and further bowel and bladder toxicity is reduced in the setting of salvage radiotherapy,” said Dr. Sandhu, an associate professor and consultant medical oncologist at Peter MacCallum Cancer Centre, Victoria, Australia.

The aim of the RADICALS-RT study was to clarify the optimal timing for radiotherapy after radical prostatectomy in men with prostate cancer, which previously had been uncertain.

In the study, 697 patients were randomly assigned to adjuvant radiotherapy and 699 to observation with salvage radiotherapy. Participants had undergone radical prostatectomy; had a postoperative prostate-specific antigen (PSA) level ≤ 0.2 ng/mL; and at least one risk factor for cancer relapse, including pathologic T-stage III or IV, Gleason score of 7-10, positive margins, or preoperative PSA ≥ 10 ng/mL.

Patients in the observation arm received salvage radiotherapy if they experienced two consecutive PSA increases ≥ 0.1 ng/mL or three consecutive rises.

Overall, the investigators found similar rates of 10-year freedom from distant metastases in both arms: 93% in the adjuvant radiotherapy group vs. 90% in the observation group (hazard ratio, 0.68; P = .095). The 10-year overall survival rates were similar as well: 88% in the adjuvant radiotherapy group and 87% in the observation group (HR, 0.98; P = .92).

However, self-reported urinary and fecal incontinence rates at 1 year were significantly higher in the adjuvant radiotherapy group vs. the observation group, 60% of whom had not received salvage radiotherapy at that time.

Secondary outcome measures, including biochemical progression-free survival and time to further hormone therapy, were also similar in the treatment and observation arms.

Overall, the trial results “support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention, “ concluded Dr. Clarke, a professor and consultant urologist at the Christie Hospital and Salford Royal Hospital, Manchester, England.

And when biochemical recurrence does occur, Dr. Sandhu noted that prostate-specific membrane antigen PET is increasingly used in practice to help “define the extent of disease” and “tailor radiation fields.”

Dr. Clarke reported serving on advisory boards for Janssen, Astellas, and Bayer. Dr. Sandhu reported receiving research grant support and/or serving as a consultant or adviser for Advanced Accelerator Application (a Novartis company), AstraZeneca, Merck Sharp and Dohme, Roche/Genentech, Amgen, Pfizer, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, and Sehnwa.

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

Adjuvant radiotherapy after radical prostatectomy provided no meaningful benefit in patients with prostate cancer but increased the risk for urinary and bowel morbidity, compared with men followed with observation alone, according to the latest results from the phase 3 RADICALS-RT trial.

The new findings showed no difference in the rate of 10-year freedom from distant metastases or overall survival in patients who received adjuvant radiotherapy vs. those who underwent observation with salvage radiotherapy if their disease progressed and provided further confirmation of earlier results reported in The Lancet in 2020.

Observation with early salvage radiotherapy in cases of biochemical failure should be the standard of care, concluded study coauthor Noel Clarke, MBBS, who presented the results at the annual meeting of the European Society for Medical Oncology.

Invited discussant and session cochair Shahneed Sandhu, MBBS, said that the findings definitively confirm the value of observation with salvage radiotherapy over adjuvant radiotherapy in this patient population.

“The approach of early salvage radiotherapy spared morbidity [from] radiation in the vast majority of patients, and further bowel and bladder toxicity is reduced in the setting of salvage radiotherapy,” said Dr. Sandhu, an associate professor and consultant medical oncologist at Peter MacCallum Cancer Centre, Victoria, Australia.

The aim of the RADICALS-RT study was to clarify the optimal timing for radiotherapy after radical prostatectomy in men with prostate cancer, which previously had been uncertain.

In the study, 697 patients were randomly assigned to adjuvant radiotherapy and 699 to observation with salvage radiotherapy. Participants had undergone radical prostatectomy; had a postoperative prostate-specific antigen (PSA) level ≤ 0.2 ng/mL; and at least one risk factor for cancer relapse, including pathologic T-stage III or IV, Gleason score of 7-10, positive margins, or preoperative PSA ≥ 10 ng/mL.

Patients in the observation arm received salvage radiotherapy if they experienced two consecutive PSA increases ≥ 0.1 ng/mL or three consecutive rises.

Overall, the investigators found similar rates of 10-year freedom from distant metastases in both arms: 93% in the adjuvant radiotherapy group vs. 90% in the observation group (hazard ratio, 0.68; P = .095). The 10-year overall survival rates were similar as well: 88% in the adjuvant radiotherapy group and 87% in the observation group (HR, 0.98; P = .92).

However, self-reported urinary and fecal incontinence rates at 1 year were significantly higher in the adjuvant radiotherapy group vs. the observation group, 60% of whom had not received salvage radiotherapy at that time.

Secondary outcome measures, including biochemical progression-free survival and time to further hormone therapy, were also similar in the treatment and observation arms.

Overall, the trial results “support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention, “ concluded Dr. Clarke, a professor and consultant urologist at the Christie Hospital and Salford Royal Hospital, Manchester, England.

And when biochemical recurrence does occur, Dr. Sandhu noted that prostate-specific membrane antigen PET is increasingly used in practice to help “define the extent of disease” and “tailor radiation fields.”

Dr. Clarke reported serving on advisory boards for Janssen, Astellas, and Bayer. Dr. Sandhu reported receiving research grant support and/or serving as a consultant or adviser for Advanced Accelerator Application (a Novartis company), AstraZeneca, Merck Sharp and Dohme, Roche/Genentech, Amgen, Pfizer, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, and Sehnwa.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Fatigue and poor physical functioning before starting treatment for early breast cancer were independently associated with chemotherapy dose reductions and postchemotherapy toxicities, a new analysis found.

Baseline quality-of-life measures, most often fatigue and physical functioning, have “been associated with survival in various cancers,” the authors explain. These latest findings signal that assessing fatigue and physical functioning prior to treatment “could help to identify patients who are at risk for poor chemotherapy tolerability.”

The findings were published online in the journal Cancer.

Although quality of life is recognized as a predictor of survival in patients with advanced cancer, the evidence is less clear in early-stage breast cancer.

To understand the role quality-of-life measures play in early breast cancer, the investigators performed an ancillary analysis of the French Cancer and Toxicities (CANTO) study, which enrolled women with newly diagnosed stage I-III invasive breast cancer at 26 centers in France.

The ancillary CANTO‐PRED study was designed to explore the association between baseline quality of life measures and chemotherapy dose reductions and postchemotherapy toxicities among 3,079 patients with early breast cancer. This included 718 patients who received chemotherapy in the neoadjuvant setting and 2,361 who received chemotherapy as adjuvant treatment.

Most patients received taxanes (94.2%) and/or anthracyclines (90.5%). Other major adjuvant treatments were breast radiation therapy (92.6%), trastuzumab (21%), and endocrine therapy (74%), and all women underwent either breast-conserving surgery (74%) and/or lymph node dissection (60%). Fatigue and physical functioning were measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.

Among the 3,079 patients, 15.5% experienced chemotherapy dose reductions and 31% developed postchemotherapy toxicities.

After multivariable adjustment for clinical and patient factors, those with baseline fatigue scores greater than 39 (vs. 39 or less) had higher odds of chemotherapy dose reductions (odds ratio, 1.43) and postchemotherapy toxicities (OR, 1.32). Those with baseline physical functioning scores less than 83 (vs. 83 or higher) also had higher odds of chemotherapy dose reductions (OR, 1.54) and postchemotherapy toxicities (OR, 1.50), the authors found.

In addition, cognitive functioning, pain, sleep disturbances, and appetite loss dimensions were associated with both chemotherapy dose reductions and postchemotherapy toxicities, whereas nausea, vomiting, and dyspnea were associated with postchemotherapy toxicities.

The researchers also found that performance status was not associated with chemotherapy dose reductions or postchemotherapy toxicities, suggesting patient-reported quality of life may be a better predictor of outcomes, the authors said.

“The ability to predict important toxicities with baseline information could lead to improvements in the prevention and management of adverse treatment effects by targeting a group of patients who may need [dose reductions] or may have residual toxicities,” the authors concluded.

This study was funded by the French National Research Agency. The authors reported various relevant financial relationships.
 

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

Fatigue and poor physical functioning before starting treatment for early breast cancer were independently associated with chemotherapy dose reductions and postchemotherapy toxicities, a new analysis found.

Baseline quality-of-life measures, most often fatigue and physical functioning, have “been associated with survival in various cancers,” the authors explain. These latest findings signal that assessing fatigue and physical functioning prior to treatment “could help to identify patients who are at risk for poor chemotherapy tolerability.”

The findings were published online in the journal Cancer.

Although quality of life is recognized as a predictor of survival in patients with advanced cancer, the evidence is less clear in early-stage breast cancer.

To understand the role quality-of-life measures play in early breast cancer, the investigators performed an ancillary analysis of the French Cancer and Toxicities (CANTO) study, which enrolled women with newly diagnosed stage I-III invasive breast cancer at 26 centers in France.

The ancillary CANTO‐PRED study was designed to explore the association between baseline quality of life measures and chemotherapy dose reductions and postchemotherapy toxicities among 3,079 patients with early breast cancer. This included 718 patients who received chemotherapy in the neoadjuvant setting and 2,361 who received chemotherapy as adjuvant treatment.

Most patients received taxanes (94.2%) and/or anthracyclines (90.5%). Other major adjuvant treatments were breast radiation therapy (92.6%), trastuzumab (21%), and endocrine therapy (74%), and all women underwent either breast-conserving surgery (74%) and/or lymph node dissection (60%). Fatigue and physical functioning were measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.

Among the 3,079 patients, 15.5% experienced chemotherapy dose reductions and 31% developed postchemotherapy toxicities.

After multivariable adjustment for clinical and patient factors, those with baseline fatigue scores greater than 39 (vs. 39 or less) had higher odds of chemotherapy dose reductions (odds ratio, 1.43) and postchemotherapy toxicities (OR, 1.32). Those with baseline physical functioning scores less than 83 (vs. 83 or higher) also had higher odds of chemotherapy dose reductions (OR, 1.54) and postchemotherapy toxicities (OR, 1.50), the authors found.

In addition, cognitive functioning, pain, sleep disturbances, and appetite loss dimensions were associated with both chemotherapy dose reductions and postchemotherapy toxicities, whereas nausea, vomiting, and dyspnea were associated with postchemotherapy toxicities.

The researchers also found that performance status was not associated with chemotherapy dose reductions or postchemotherapy toxicities, suggesting patient-reported quality of life may be a better predictor of outcomes, the authors said.

“The ability to predict important toxicities with baseline information could lead to improvements in the prevention and management of adverse treatment effects by targeting a group of patients who may need [dose reductions] or may have residual toxicities,” the authors concluded.

This study was funded by the French National Research Agency. The authors reported various relevant financial relationships.
 

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

Fatigue and poor physical functioning before starting treatment for early breast cancer were independently associated with chemotherapy dose reductions and postchemotherapy toxicities, a new analysis found.

Baseline quality-of-life measures, most often fatigue and physical functioning, have “been associated with survival in various cancers,” the authors explain. These latest findings signal that assessing fatigue and physical functioning prior to treatment “could help to identify patients who are at risk for poor chemotherapy tolerability.”

The findings were published online in the journal Cancer.

Although quality of life is recognized as a predictor of survival in patients with advanced cancer, the evidence is less clear in early-stage breast cancer.

To understand the role quality-of-life measures play in early breast cancer, the investigators performed an ancillary analysis of the French Cancer and Toxicities (CANTO) study, which enrolled women with newly diagnosed stage I-III invasive breast cancer at 26 centers in France.

The ancillary CANTO‐PRED study was designed to explore the association between baseline quality of life measures and chemotherapy dose reductions and postchemotherapy toxicities among 3,079 patients with early breast cancer. This included 718 patients who received chemotherapy in the neoadjuvant setting and 2,361 who received chemotherapy as adjuvant treatment.

Most patients received taxanes (94.2%) and/or anthracyclines (90.5%). Other major adjuvant treatments were breast radiation therapy (92.6%), trastuzumab (21%), and endocrine therapy (74%), and all women underwent either breast-conserving surgery (74%) and/or lymph node dissection (60%). Fatigue and physical functioning were measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30.

Among the 3,079 patients, 15.5% experienced chemotherapy dose reductions and 31% developed postchemotherapy toxicities.

After multivariable adjustment for clinical and patient factors, those with baseline fatigue scores greater than 39 (vs. 39 or less) had higher odds of chemotherapy dose reductions (odds ratio, 1.43) and postchemotherapy toxicities (OR, 1.32). Those with baseline physical functioning scores less than 83 (vs. 83 or higher) also had higher odds of chemotherapy dose reductions (OR, 1.54) and postchemotherapy toxicities (OR, 1.50), the authors found.

In addition, cognitive functioning, pain, sleep disturbances, and appetite loss dimensions were associated with both chemotherapy dose reductions and postchemotherapy toxicities, whereas nausea, vomiting, and dyspnea were associated with postchemotherapy toxicities.

The researchers also found that performance status was not associated with chemotherapy dose reductions or postchemotherapy toxicities, suggesting patient-reported quality of life may be a better predictor of outcomes, the authors said.

“The ability to predict important toxicities with baseline information could lead to improvements in the prevention and management of adverse treatment effects by targeting a group of patients who may need [dose reductions] or may have residual toxicities,” the authors concluded.

This study was funded by the French National Research Agency. The authors reported various relevant financial relationships.
 

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

The Food and Drug Administration is moving to further restrict the use of certain PARP inhibitors in patients with ovarian cancer, citing recent data showing an increased risk for death with the agents versus chemotherapy.

These restrictions could mean bankruptcy for one company.

Earlier this year, several companies voluntarily withdrew their respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.

Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.

The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.

On Nov. 11, GSK announced that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.

The prescribing change was based on an FDA review of the final overall survival analysis of the NOVA phase 3 trial, which served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.

The company noted, however, that its first-line indication remains unchanged.

The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S. Securities and Exchange Commission filing from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.

According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy.

In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA. According to the company, among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”

Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.

Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.

However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an earlier report, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”

The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”

The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”

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

The Food and Drug Administration is moving to further restrict the use of certain PARP inhibitors in patients with ovarian cancer, citing recent data showing an increased risk for death with the agents versus chemotherapy.

These restrictions could mean bankruptcy for one company.

Earlier this year, several companies voluntarily withdrew their respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.

Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.

The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.

On Nov. 11, GSK announced that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.

The prescribing change was based on an FDA review of the final overall survival analysis of the NOVA phase 3 trial, which served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.

The company noted, however, that its first-line indication remains unchanged.

The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S. Securities and Exchange Commission filing from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.

According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy.

In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA. According to the company, among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”

Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.

Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.

However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an earlier report, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”

The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”

The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”

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

The Food and Drug Administration is moving to further restrict the use of certain PARP inhibitors in patients with ovarian cancer, citing recent data showing an increased risk for death with the agents versus chemotherapy.

These restrictions could mean bankruptcy for one company.

Earlier this year, several companies voluntarily withdrew their respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.

Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.

The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.

On Nov. 11, GSK announced that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.

The prescribing change was based on an FDA review of the final overall survival analysis of the NOVA phase 3 trial, which served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.

The company noted, however, that its first-line indication remains unchanged.

The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S. Securities and Exchange Commission filing from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.

According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy.

In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA. According to the company, among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”

Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.

Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.

However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an earlier report, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”

The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”

The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”

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

A “plethora of new agents” has transformed the treatment landscape for relapsed/refractory mantle cell lymphoma (R/RMCL) in recent years, according to an updated literature review that also included a proposed new treatment algorithm and identified areas for further investigation.

Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.

The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.

“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.

Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.

“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.

Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”

Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.

These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.

Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.

Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.

For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).

Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:

“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”

For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.

“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”

Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.

“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.

For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.

A “plethora of new agents” has transformed the treatment landscape for relapsed/refractory mantle cell lymphoma (R/RMCL) in recent years, according to an updated literature review that also included a proposed new treatment algorithm and identified areas for further investigation.

Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.

The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.

“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.

Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.

“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.

Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”

Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.

These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.

Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.

Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.

For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).

Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:

“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”

For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.

“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”

Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.

“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.

For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.

A “plethora of new agents” has transformed the treatment landscape for relapsed/refractory mantle cell lymphoma (R/RMCL) in recent years, according to an updated literature review that also included a proposed new treatment algorithm and identified areas for further investigation.

Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.

The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.

“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.

Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.

“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.

Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”

Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.

These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.

Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.

Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.

For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).

Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:

“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”

For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.

“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”

Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.

“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.

For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.

New guidelines highlight the role that integrative pain management techniques, such as massage, acupuncture, and music therapy, can play in relieving certain types of cancer pain in adults.

The recommendations, published in the Journal of Clinical Oncology, represent a joint effort between the American Society of Clinical Oncology (ASCO) and the Society of Integrative Oncology (SIO) to guide clinicians on how best to weave various nonpharmacologic pain management strategies into cancer care.

“Pain is a clinical challenge for many oncology patients and clinicians, and there’s a growing body of evidence showing that integrative therapies can be useful in pain management,” Heather Greenlee, ND, PhD, explained in a press release.

However, clear clinical guidance as to when and when not to use these approaches is lacking, said Dr. Greenlee, cochair of the SIO Clinical Practice Guideline Committee.

Previous guidelines from ASCO on managing chronic cancer-related pain largely focused on diagnosing pain and on pharmacologic interventions, and they touched only on evidence related to nonpharmacologic options.

The new guideline “takes a deeper dive on the use of integrative therapies, which is important because clinicians and patients need to have access to the latest evidence-based information to make clinical decisions,” noted Jun H. Mao, MD, SIO-ASCO panel cochair.

In the guidance, the expert panel addresses two core questions: What mind-body therapies are recommended for managing pain experienced by adult and pediatric patients diagnosed with cancer, and what natural products are recommended for managing pain experienced by adult and pediatric patients diagnosed with cancer?

The panel conducted a literature search and identified 277 relevant studies. They included systematic reviews and randomized controlled trials published between 1990 and 2021 that evaluated outcomes related to pain intensity, symptom relief, and adverse events. After reaching a consensus, the expert panel made recommendations on the basis of the strength of the available evidence.

Regarding modalities for which there was stronger evidence, the panel highlighted several recommendations regarding acupuncture, reflexology, hypnosis, and massage.

The panel determined, for instance, that acupuncture should be offered for aromatase-related joint pain in patients with breast cancer and that it can be offered for general or musculoskeletal pain from cancer. It recommended reflexology or acupressure for pain experienced during systemic therapy for cancer. Hypnosis is an option for patients experiencing procedural pain in cancer treatment or diagnostic workups, and massage is an option for pain experienced during palliative or hospice care or following breast cancer treatment.

These recommendations were considered moderate in strength and were based on intermediate levels of evidence that demonstrated that the benefits outweighed risks.

The panel added several recommendations it deemed to be weak in strength and that were based on low-quality evidence. These include Hatha yoga for patients experiencing pain after treatment for breast or head and neck cancers, and music therapy for patients experiencing pain from cancer surgery.

The experts also identified areas “potentially relevant to cancer care but needing more research,” such as the safety and efficacy of natural products, including omega-3 fatty acids and glutamine, and determined that there is insufficient or inconclusive evidence to make recommendations for pediatric patients.

“With improved oncology treatments such as immunotherapy and targeted therapy, more patients diagnosed with cancer are living longer; therefore, pain and symptom management is critical for improving quality of life,” Dr. Mao, chief of integrative medicine at Memorial Sloan Kettering Cancer Center, New York, said in an interview. “The SIO-ASCO clinical guideline will provide very timely recommendations for physicians to incorporate nonpharmacological treatments such as acupuncture and massage to improve pain management for patients impacted by cancer.”

However, clinical uptake of such treatments “is always a concern,” said panel cochair Eduardo Bruera, MD, of MD Anderson Cancer Center, Houston. “We are hoping that by showing the growing evidence that is out there, health care systems will start hiring these kinds of practitioners and insurance systems will start covering these treatments, because more and more, these are being shown to be effective at managing pain for cancer populations,” Dr. Bruera said.

The SIO-ASCO panel’s work was supported by a grant from the Samueli Foundation to the Society for Integrative Oncology.

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

New guidelines highlight the role that integrative pain management techniques, such as massage, acupuncture, and music therapy, can play in relieving certain types of cancer pain in adults.

The recommendations, published in the Journal of Clinical Oncology, represent a joint effort between the American Society of Clinical Oncology (ASCO) and the Society of Integrative Oncology (SIO) to guide clinicians on how best to weave various nonpharmacologic pain management strategies into cancer care.

“Pain is a clinical challenge for many oncology patients and clinicians, and there’s a growing body of evidence showing that integrative therapies can be useful in pain management,” Heather Greenlee, ND, PhD, explained in a press release.

However, clear clinical guidance as to when and when not to use these approaches is lacking, said Dr. Greenlee, cochair of the SIO Clinical Practice Guideline Committee.

Previous guidelines from ASCO on managing chronic cancer-related pain largely focused on diagnosing pain and on pharmacologic interventions, and they touched only on evidence related to nonpharmacologic options.

The new guideline “takes a deeper dive on the use of integrative therapies, which is important because clinicians and patients need to have access to the latest evidence-based information to make clinical decisions,” noted Jun H. Mao, MD, SIO-ASCO panel cochair.

In the guidance, the expert panel addresses two core questions: What mind-body therapies are recommended for managing pain experienced by adult and pediatric patients diagnosed with cancer, and what natural products are recommended for managing pain experienced by adult and pediatric patients diagnosed with cancer?

The panel conducted a literature search and identified 277 relevant studies. They included systematic reviews and randomized controlled trials published between 1990 and 2021 that evaluated outcomes related to pain intensity, symptom relief, and adverse events. After reaching a consensus, the expert panel made recommendations on the basis of the strength of the available evidence.

Regarding modalities for which there was stronger evidence, the panel highlighted several recommendations regarding acupuncture, reflexology, hypnosis, and massage.

The panel determined, for instance, that acupuncture should be offered for aromatase-related joint pain in patients with breast cancer and that it can be offered for general or musculoskeletal pain from cancer. It recommended reflexology or acupressure for pain experienced during systemic therapy for cancer. Hypnosis is an option for patients experiencing procedural pain in cancer treatment or diagnostic workups, and massage is an option for pain experienced during palliative or hospice care or following breast cancer treatment.

These recommendations were considered moderate in strength and were based on intermediate levels of evidence that demonstrated that the benefits outweighed risks.

The panel added several recommendations it deemed to be weak in strength and that were based on low-quality evidence. These include Hatha yoga for patients experiencing pain after treatment for breast or head and neck cancers, and music therapy for patients experiencing pain from cancer surgery.

The experts also identified areas “potentially relevant to cancer care but needing more research,” such as the safety and efficacy of natural products, including omega-3 fatty acids and glutamine, and determined that there is insufficient or inconclusive evidence to make recommendations for pediatric patients.

“With improved oncology treatments such as immunotherapy and targeted therapy, more patients diagnosed with cancer are living longer; therefore, pain and symptom management is critical for improving quality of life,” Dr. Mao, chief of integrative medicine at Memorial Sloan Kettering Cancer Center, New York, said in an interview. “The SIO-ASCO clinical guideline will provide very timely recommendations for physicians to incorporate nonpharmacological treatments such as acupuncture and massage to improve pain management for patients impacted by cancer.”

However, clinical uptake of such treatments “is always a concern,” said panel cochair Eduardo Bruera, MD, of MD Anderson Cancer Center, Houston. “We are hoping that by showing the growing evidence that is out there, health care systems will start hiring these kinds of practitioners and insurance systems will start covering these treatments, because more and more, these are being shown to be effective at managing pain for cancer populations,” Dr. Bruera said.

The SIO-ASCO panel’s work was supported by a grant from the Samueli Foundation to the Society for Integrative Oncology.

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

New guidelines highlight the role that integrative pain management techniques, such as massage, acupuncture, and music therapy, can play in relieving certain types of cancer pain in adults.

The recommendations, published in the Journal of Clinical Oncology, represent a joint effort between the American Society of Clinical Oncology (ASCO) and the Society of Integrative Oncology (SIO) to guide clinicians on how best to weave various nonpharmacologic pain management strategies into cancer care.

“Pain is a clinical challenge for many oncology patients and clinicians, and there’s a growing body of evidence showing that integrative therapies can be useful in pain management,” Heather Greenlee, ND, PhD, explained in a press release.

However, clear clinical guidance as to when and when not to use these approaches is lacking, said Dr. Greenlee, cochair of the SIO Clinical Practice Guideline Committee.

Previous guidelines from ASCO on managing chronic cancer-related pain largely focused on diagnosing pain and on pharmacologic interventions, and they touched only on evidence related to nonpharmacologic options.

The new guideline “takes a deeper dive on the use of integrative therapies, which is important because clinicians and patients need to have access to the latest evidence-based information to make clinical decisions,” noted Jun H. Mao, MD, SIO-ASCO panel cochair.

In the guidance, the expert panel addresses two core questions: What mind-body therapies are recommended for managing pain experienced by adult and pediatric patients diagnosed with cancer, and what natural products are recommended for managing pain experienced by adult and pediatric patients diagnosed with cancer?

The panel conducted a literature search and identified 277 relevant studies. They included systematic reviews and randomized controlled trials published between 1990 and 2021 that evaluated outcomes related to pain intensity, symptom relief, and adverse events. After reaching a consensus, the expert panel made recommendations on the basis of the strength of the available evidence.

Regarding modalities for which there was stronger evidence, the panel highlighted several recommendations regarding acupuncture, reflexology, hypnosis, and massage.

The panel determined, for instance, that acupuncture should be offered for aromatase-related joint pain in patients with breast cancer and that it can be offered for general or musculoskeletal pain from cancer. It recommended reflexology or acupressure for pain experienced during systemic therapy for cancer. Hypnosis is an option for patients experiencing procedural pain in cancer treatment or diagnostic workups, and massage is an option for pain experienced during palliative or hospice care or following breast cancer treatment.

These recommendations were considered moderate in strength and were based on intermediate levels of evidence that demonstrated that the benefits outweighed risks.

The panel added several recommendations it deemed to be weak in strength and that were based on low-quality evidence. These include Hatha yoga for patients experiencing pain after treatment for breast or head and neck cancers, and music therapy for patients experiencing pain from cancer surgery.

The experts also identified areas “potentially relevant to cancer care but needing more research,” such as the safety and efficacy of natural products, including omega-3 fatty acids and glutamine, and determined that there is insufficient or inconclusive evidence to make recommendations for pediatric patients.

“With improved oncology treatments such as immunotherapy and targeted therapy, more patients diagnosed with cancer are living longer; therefore, pain and symptom management is critical for improving quality of life,” Dr. Mao, chief of integrative medicine at Memorial Sloan Kettering Cancer Center, New York, said in an interview. “The SIO-ASCO clinical guideline will provide very timely recommendations for physicians to incorporate nonpharmacological treatments such as acupuncture and massage to improve pain management for patients impacted by cancer.”

However, clinical uptake of such treatments “is always a concern,” said panel cochair Eduardo Bruera, MD, of MD Anderson Cancer Center, Houston. “We are hoping that by showing the growing evidence that is out there, health care systems will start hiring these kinds of practitioners and insurance systems will start covering these treatments, because more and more, these are being shown to be effective at managing pain for cancer populations,” Dr. Bruera said.

The SIO-ASCO panel’s work was supported by a grant from the Samueli Foundation to the Society for Integrative Oncology.

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

A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, said the authors.

Viktor Cap/Thinkstock

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, PhD, of Cancer Council Victoria, Melbourne, and colleagues reported on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization – a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single-nucleotide polymorphisms (SNPs) associated in UK Biobank [genomewide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio, 0.59), the team reported. Genetically predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs. 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone receptor–negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6,667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre-/perimenopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors noted, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers reported, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggested that “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. Dr. Dixon-Suen reported no relevant financial relationships. Several coauthors disclosed relationships with industry.

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

A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, said the authors.

Viktor Cap/Thinkstock

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, PhD, of Cancer Council Victoria, Melbourne, and colleagues reported on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization – a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single-nucleotide polymorphisms (SNPs) associated in UK Biobank [genomewide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio, 0.59), the team reported. Genetically predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs. 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone receptor–negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6,667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre-/perimenopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors noted, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers reported, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggested that “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. Dr. Dixon-Suen reported no relevant financial relationships. Several coauthors disclosed relationships with industry.

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

A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, said the authors.

Viktor Cap/Thinkstock

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, PhD, of Cancer Council Victoria, Melbourne, and colleagues reported on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization – a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single-nucleotide polymorphisms (SNPs) associated in UK Biobank [genomewide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio, 0.59), the team reported. Genetically predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs. 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone receptor–negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6,667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre-/perimenopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors noted, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers reported, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggested that “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. Dr. Dixon-Suen reported no relevant financial relationships. Several coauthors disclosed relationships with industry.

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