Key clinical point: Patients with germline (g) BRCA1/2-associated primary breast cancer (BC), particularly those with gBRCA2 pathogenic mutations, faced a moderately increased risk of developing contralateral breast cancer (CBC) after receiving adjuvant radiotherapy.

Major finding: The risk for invasive and in situ CBC increased by 44% in patients with gBRCA1/2 mutations who did vs did not receive radiotherapy (adjusted hazard ratio [HR] 1.44;  95% CI 1.12-1.86), with the risk being even more prominent in gBRCA2 pathogenic variant carriers (adjusted HR 1.77;  95% CI 1.13-2.77).

Study details: Findings are from an analysis including 3602 patients with gBRCA1/2-associated primary BC from the prospective international BRCA1/2 Carrier Cohort Study, of whom 64% of patients received adjuvant radiotherapy.

Disclosures: This study did not receive any specific external funding. DG Evans reported ties with AstraZeneca and AmGen, K Kast declared ties with Roche Pharma AG, and J Simard declared holding patents related to BRCA1 and BRCA2.

Source: van Barele M et al. Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant. J Natl Cancer Inst. 2023 (Jun 27). Doi: 10.1093/jnci/djad116

Key clinical point: Patients with germline (g) BRCA1/2-associated primary breast cancer (BC), particularly those with gBRCA2 pathogenic mutations, faced a moderately increased risk of developing contralateral breast cancer (CBC) after receiving adjuvant radiotherapy.

Major finding: The risk for invasive and in situ CBC increased by 44% in patients with gBRCA1/2 mutations who did vs did not receive radiotherapy (adjusted hazard ratio [HR] 1.44;  95% CI 1.12-1.86), with the risk being even more prominent in gBRCA2 pathogenic variant carriers (adjusted HR 1.77;  95% CI 1.13-2.77).

Study details: Findings are from an analysis including 3602 patients with gBRCA1/2-associated primary BC from the prospective international BRCA1/2 Carrier Cohort Study, of whom 64% of patients received adjuvant radiotherapy.

Disclosures: This study did not receive any specific external funding. DG Evans reported ties with AstraZeneca and AmGen, K Kast declared ties with Roche Pharma AG, and J Simard declared holding patents related to BRCA1 and BRCA2.

Source: van Barele M et al. Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant. J Natl Cancer Inst. 2023 (Jun 27). Doi: 10.1093/jnci/djad116

Key clinical point: Patients with germline (g) BRCA1/2-associated primary breast cancer (BC), particularly those with gBRCA2 pathogenic mutations, faced a moderately increased risk of developing contralateral breast cancer (CBC) after receiving adjuvant radiotherapy.

Major finding: The risk for invasive and in situ CBC increased by 44% in patients with gBRCA1/2 mutations who did vs did not receive radiotherapy (adjusted hazard ratio [HR] 1.44;  95% CI 1.12-1.86), with the risk being even more prominent in gBRCA2 pathogenic variant carriers (adjusted HR 1.77;  95% CI 1.13-2.77).

Study details: Findings are from an analysis including 3602 patients with gBRCA1/2-associated primary BC from the prospective international BRCA1/2 Carrier Cohort Study, of whom 64% of patients received adjuvant radiotherapy.

Disclosures: This study did not receive any specific external funding. DG Evans reported ties with AstraZeneca and AmGen, K Kast declared ties with Roche Pharma AG, and J Simard declared holding patents related to BRCA1 and BRCA2.

Source: van Barele M et al. Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant. J Natl Cancer Inst. 2023 (Jun 27). Doi: 10.1093/jnci/djad116

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) breast cancer (BC) experienced very low locoregional recurrence (LRR) events and comparable invasive disease-free survival (iDFS) outcomes both with and without receiving regional nodal irradiation (RNI) after surgery.

Major finding: The cumulative incidence of LRR at 5 years was low among patients who underwent breast-conserving surgery and radiotherapy with RNI (0.85%), breast-conserving surgery and radiotherapy without RNI (0.55%), mastectomy followed by radiotherapy (0.11%), or mastectomy without radiotherapy (1.7%). Receiving RNI was not associated with better iDFS outcomes (P > .1 for both pre- and postmenopausal women).

Study details: Findings are from the secondary analysis of the SWOG S1007 trial including 4871 women with HR+/ERBB2− node-positive BC, of whom 2274 women received RNI.

Disclosures: This study was supported by the US National Institutes of Health (NIH) and other sources. Some authors declared serving as consultants or receiving grants and personal fees from various sources, including NIH.

Source: Jagsi R et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. 2023 (Jul 6). Doi: 10.1001/jamaoncol.2023.1984

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) breast cancer (BC) experienced very low locoregional recurrence (LRR) events and comparable invasive disease-free survival (iDFS) outcomes both with and without receiving regional nodal irradiation (RNI) after surgery.

Major finding: The cumulative incidence of LRR at 5 years was low among patients who underwent breast-conserving surgery and radiotherapy with RNI (0.85%), breast-conserving surgery and radiotherapy without RNI (0.55%), mastectomy followed by radiotherapy (0.11%), or mastectomy without radiotherapy (1.7%). Receiving RNI was not associated with better iDFS outcomes (P > .1 for both pre- and postmenopausal women).

Study details: Findings are from the secondary analysis of the SWOG S1007 trial including 4871 women with HR+/ERBB2− node-positive BC, of whom 2274 women received RNI.

Disclosures: This study was supported by the US National Institutes of Health (NIH) and other sources. Some authors declared serving as consultants or receiving grants and personal fees from various sources, including NIH.

Source: Jagsi R et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. 2023 (Jul 6). Doi: 10.1001/jamaoncol.2023.1984

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) breast cancer (BC) experienced very low locoregional recurrence (LRR) events and comparable invasive disease-free survival (iDFS) outcomes both with and without receiving regional nodal irradiation (RNI) after surgery.

Major finding: The cumulative incidence of LRR at 5 years was low among patients who underwent breast-conserving surgery and radiotherapy with RNI (0.85%), breast-conserving surgery and radiotherapy without RNI (0.55%), mastectomy followed by radiotherapy (0.11%), or mastectomy without radiotherapy (1.7%). Receiving RNI was not associated with better iDFS outcomes (P > .1 for both pre- and postmenopausal women).

Study details: Findings are from the secondary analysis of the SWOG S1007 trial including 4871 women with HR+/ERBB2− node-positive BC, of whom 2274 women received RNI.

Disclosures: This study was supported by the US National Institutes of Health (NIH) and other sources. Some authors declared serving as consultants or receiving grants and personal fees from various sources, including NIH.

Source: Jagsi R et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. 2023 (Jul 6). Doi: 10.1001/jamaoncol.2023.1984

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

After 15 years of researching what works well in oncology – and where the field has gone awry – Christopher Booth, MD, had a career moment.

“As I approached mid-career, I realized publishing and describing problems wasn’t fulfilling. It wasn’t doing enough,” recalled Dr. Booth, an oncologist and professor at Queen’s University, Kingston, Ont. “I wanted to change mindsets and change systems so that things actually improved for the better for patients.”

His colleague, Bishal Gyawali, MD, PhD, described a similar epiphany. As a trainee, he noticed that the real-world effects of some so-called blockbuster cancer drugs too often failed to measure up to the hype.

“I realized we were lacking common sense in oncology,” said Dr. Gyawali, a medical oncologist and assistant professor at Queen’s University.

In 2019, Dr. Gyawali launched a Medscape column addressing what he considers to be that lack of common sense, and in 2022, he and Dr. Booth published a similarly titled opinion piece in Nature Medicine. The core idea: The cancer community needs to prioritize cancer treatments that benefit patients, treatments that meaningfully improve survival and quality of life.

Aaron Goodman, MD, a hematologist and associate professor at UC San Diego Health, was on the same page. He’d been interested in the evidence-based medicine movement since his time as a hematology fellow when that movement was “a bit of a counterculture,” he explained.

Dr. Goodman and Dr. Booth connected through their common interests and collaborated on a 2021 paper exploring the discomfort clinicians might feel when a patient’s needs fall on the “edge of oncology”: that is, when the guideline-recommended standard of care offers marginal benefit, at best, and could, at worst, cause patient harm.

“We said, ‘Now is the time to make change,’ ” he recalled. It was time to stop talking and do something.
 

Common sense and a common purpose

Dr. Booth, Dr. Gyawali, and Dr. Goodman joined forces and, with the backing of a philanthropist who had experience as a patient with cancer, convened an organizing committee of more than 30 like-minded oncologists and patient advocates from across the globe.

The group convened for a 3-day “meeting of the minds” in Kingston in April and laid out their intentions in a position paper published online in The Lancet Oncology.

The publication marks the official launch of an ambitious, multipronged, global initiative to enact change: Common Sense Oncology, a new patient-centered movement in cancer care.

In their paper, the committee outline the vision for Common Sense Oncology. The mission: prioritize patient-centered and equitable care by focusing on treatments that improve survival and quality of life, communication that promotes informed decision-making, and systems that ensure access to all patients.

However, increasingly, the cancer community faces a “troubling paradox,” the team wrote in The Lancet. In some instance, treatments that bring minimal benefit are overused while those that can make a meaningful difference in patients’ lives are not accessible to most worldwide.

One reason for this shift: Commercial interests, rather than patient interests, appear to be driving cancer research and care. The team explained, for instance, that over the past few decades, clinical trials have largely pivoted from publicly funded efforts to industry funded ones “designed to achieve regulatory approval or commercial advantage, [often] at the expense of investigating new approaches to surgery, radiotherapy, palliative care, and prevention.”

But “patients deserve better,” the group wrote.

The team outlined three pillars for the initiative: evidence generation, evidence interpretation, and evidence communication.

The evidence generation pillar will aim to improve trial design and reporting to prioritize outcomes that matter to patients.

“One concern is that over the last 10 years or so, most of our new treatments have had very, very small benefits, and we think the bar has dropped too low,” Dr. Booth said, explaining that many trials have moved away from focusing on improving survival and quality of life and toward detecting small differences between treatments on other endpoints – namely progression-free survival. “Those small benefits need to be balanced against the very real risks to our patients.”

The evidence interpretation pillar will aim to foster critical thinking so that clinicians can better identify poorly designed or reported trials and help patients make more informed decisions.

Lastly, the evidence communication pillar will focus on fostering better communication about treatment options among patients, the public, and policymakers. Without clear and thoughtful communication, patients may have unrealistic expectations about the effectiveness of treatments that offer only marginal clinical benefits.

The team also emphasized a need to focus on improving global equity and access to affordable treatments so all patients can benefit from care that extends survival or quality of life.

It’s an ambitious undertaking, especially for a group of full-time clinicians, researchers, and patient advocates “volunteering their time for societal good,” said Dr. Gyawali, but the project teams intend to hit the ground running.

The team has established short-term targets, such as identifying deficiencies in data interpretation within education programs within 6 months and developing educational materials that begin to correct those deficiencies within 12 months, Dr. Booth explained. In the longer term, the team will also aim to design clinical trials that focus on patient outcomes, such as overall survival and quality of life.

Breast cancer survivor and patient advocate Michelle Tregear, PhD, who was recruited to help with Common Sense Oncology, also hopes the initiative will lead to better regulatory control that requires trial sponsors to “focus on what matters to patients, not on surrogate endpoints.”

When it comes to clinical trials, “more, more, more is not always better,” said Dr. Tregear, director of Education and Training Programs for patient advocates at the National Breast Cancer Coalition, Washington, D.C. “Industry interests are not always aligned with patient interests,” and “the system, by and large, is not addressing questions that really matter to patients and their families.”

Although “it’s a tall order to change the direction that we’re going in,” Dr. Tregear is up to the challenge of helping raise awareness, which will hopefully spur patients to demand change.

When Dr. Goodman announced the Common Sense Oncology initiative on Twitter, the news brought excitement, with many oncologists asking to join.

With its sweeping, ambitious goals, the Common Sense Oncology initiative has a long road ahead. Figuring out how to implement some of its aims in practice will take time, Dr. Booth acknowledges, and the initial launch marks the first steps, which will continue to evolve over time.

“We’re not proposing we have all the answers or that we know what every patient would want – we’re saying we’ve not done a good job of communicating to patients the relative benefits and risks of different treatments,” Dr. Booth explained. “We want to celebrate and promote what helps and speak out about what’s not in the best interest of patients.”

Dr. Goodman reported consulting fees from Seattle Genetics and speaking honoraria from Curio. Dr. Booth, Dr. Gyawali, and Dr. Tregear reported having no financial conflicts of interest.

A version of this article appeared on Medscape.com.

After 15 years of researching what works well in oncology – and where the field has gone awry – Christopher Booth, MD, had a career moment.

“As I approached mid-career, I realized publishing and describing problems wasn’t fulfilling. It wasn’t doing enough,” recalled Dr. Booth, an oncologist and professor at Queen’s University, Kingston, Ont. “I wanted to change mindsets and change systems so that things actually improved for the better for patients.”

His colleague, Bishal Gyawali, MD, PhD, described a similar epiphany. As a trainee, he noticed that the real-world effects of some so-called blockbuster cancer drugs too often failed to measure up to the hype.

“I realized we were lacking common sense in oncology,” said Dr. Gyawali, a medical oncologist and assistant professor at Queen’s University.

In 2019, Dr. Gyawali launched a Medscape column addressing what he considers to be that lack of common sense, and in 2022, he and Dr. Booth published a similarly titled opinion piece in Nature Medicine. The core idea: The cancer community needs to prioritize cancer treatments that benefit patients, treatments that meaningfully improve survival and quality of life.

Aaron Goodman, MD, a hematologist and associate professor at UC San Diego Health, was on the same page. He’d been interested in the evidence-based medicine movement since his time as a hematology fellow when that movement was “a bit of a counterculture,” he explained.

Dr. Goodman and Dr. Booth connected through their common interests and collaborated on a 2021 paper exploring the discomfort clinicians might feel when a patient’s needs fall on the “edge of oncology”: that is, when the guideline-recommended standard of care offers marginal benefit, at best, and could, at worst, cause patient harm.

“We said, ‘Now is the time to make change,’ ” he recalled. It was time to stop talking and do something.
 

Common sense and a common purpose

Dr. Booth, Dr. Gyawali, and Dr. Goodman joined forces and, with the backing of a philanthropist who had experience as a patient with cancer, convened an organizing committee of more than 30 like-minded oncologists and patient advocates from across the globe.

The group convened for a 3-day “meeting of the minds” in Kingston in April and laid out their intentions in a position paper published online in The Lancet Oncology.

The publication marks the official launch of an ambitious, multipronged, global initiative to enact change: Common Sense Oncology, a new patient-centered movement in cancer care.

In their paper, the committee outline the vision for Common Sense Oncology. The mission: prioritize patient-centered and equitable care by focusing on treatments that improve survival and quality of life, communication that promotes informed decision-making, and systems that ensure access to all patients.

However, increasingly, the cancer community faces a “troubling paradox,” the team wrote in The Lancet. In some instance, treatments that bring minimal benefit are overused while those that can make a meaningful difference in patients’ lives are not accessible to most worldwide.

One reason for this shift: Commercial interests, rather than patient interests, appear to be driving cancer research and care. The team explained, for instance, that over the past few decades, clinical trials have largely pivoted from publicly funded efforts to industry funded ones “designed to achieve regulatory approval or commercial advantage, [often] at the expense of investigating new approaches to surgery, radiotherapy, palliative care, and prevention.”

But “patients deserve better,” the group wrote.

The team outlined three pillars for the initiative: evidence generation, evidence interpretation, and evidence communication.

The evidence generation pillar will aim to improve trial design and reporting to prioritize outcomes that matter to patients.

“One concern is that over the last 10 years or so, most of our new treatments have had very, very small benefits, and we think the bar has dropped too low,” Dr. Booth said, explaining that many trials have moved away from focusing on improving survival and quality of life and toward detecting small differences between treatments on other endpoints – namely progression-free survival. “Those small benefits need to be balanced against the very real risks to our patients.”

The evidence interpretation pillar will aim to foster critical thinking so that clinicians can better identify poorly designed or reported trials and help patients make more informed decisions.

Lastly, the evidence communication pillar will focus on fostering better communication about treatment options among patients, the public, and policymakers. Without clear and thoughtful communication, patients may have unrealistic expectations about the effectiveness of treatments that offer only marginal clinical benefits.

The team also emphasized a need to focus on improving global equity and access to affordable treatments so all patients can benefit from care that extends survival or quality of life.

It’s an ambitious undertaking, especially for a group of full-time clinicians, researchers, and patient advocates “volunteering their time for societal good,” said Dr. Gyawali, but the project teams intend to hit the ground running.

The team has established short-term targets, such as identifying deficiencies in data interpretation within education programs within 6 months and developing educational materials that begin to correct those deficiencies within 12 months, Dr. Booth explained. In the longer term, the team will also aim to design clinical trials that focus on patient outcomes, such as overall survival and quality of life.

Breast cancer survivor and patient advocate Michelle Tregear, PhD, who was recruited to help with Common Sense Oncology, also hopes the initiative will lead to better regulatory control that requires trial sponsors to “focus on what matters to patients, not on surrogate endpoints.”

When it comes to clinical trials, “more, more, more is not always better,” said Dr. Tregear, director of Education and Training Programs for patient advocates at the National Breast Cancer Coalition, Washington, D.C. “Industry interests are not always aligned with patient interests,” and “the system, by and large, is not addressing questions that really matter to patients and their families.”

Although “it’s a tall order to change the direction that we’re going in,” Dr. Tregear is up to the challenge of helping raise awareness, which will hopefully spur patients to demand change.

When Dr. Goodman announced the Common Sense Oncology initiative on Twitter, the news brought excitement, with many oncologists asking to join.

With its sweeping, ambitious goals, the Common Sense Oncology initiative has a long road ahead. Figuring out how to implement some of its aims in practice will take time, Dr. Booth acknowledges, and the initial launch marks the first steps, which will continue to evolve over time.

“We’re not proposing we have all the answers or that we know what every patient would want – we’re saying we’ve not done a good job of communicating to patients the relative benefits and risks of different treatments,” Dr. Booth explained. “We want to celebrate and promote what helps and speak out about what’s not in the best interest of patients.”

Dr. Goodman reported consulting fees from Seattle Genetics and speaking honoraria from Curio. Dr. Booth, Dr. Gyawali, and Dr. Tregear reported having no financial conflicts of interest.

A version of this article appeared on Medscape.com.

After 15 years of researching what works well in oncology – and where the field has gone awry – Christopher Booth, MD, had a career moment.

“As I approached mid-career, I realized publishing and describing problems wasn’t fulfilling. It wasn’t doing enough,” recalled Dr. Booth, an oncologist and professor at Queen’s University, Kingston, Ont. “I wanted to change mindsets and change systems so that things actually improved for the better for patients.”

His colleague, Bishal Gyawali, MD, PhD, described a similar epiphany. As a trainee, he noticed that the real-world effects of some so-called blockbuster cancer drugs too often failed to measure up to the hype.

“I realized we were lacking common sense in oncology,” said Dr. Gyawali, a medical oncologist and assistant professor at Queen’s University.

In 2019, Dr. Gyawali launched a Medscape column addressing what he considers to be that lack of common sense, and in 2022, he and Dr. Booth published a similarly titled opinion piece in Nature Medicine. The core idea: The cancer community needs to prioritize cancer treatments that benefit patients, treatments that meaningfully improve survival and quality of life.

Aaron Goodman, MD, a hematologist and associate professor at UC San Diego Health, was on the same page. He’d been interested in the evidence-based medicine movement since his time as a hematology fellow when that movement was “a bit of a counterculture,” he explained.

Dr. Goodman and Dr. Booth connected through their common interests and collaborated on a 2021 paper exploring the discomfort clinicians might feel when a patient’s needs fall on the “edge of oncology”: that is, when the guideline-recommended standard of care offers marginal benefit, at best, and could, at worst, cause patient harm.

“We said, ‘Now is the time to make change,’ ” he recalled. It was time to stop talking and do something.
 

Common sense and a common purpose

Dr. Booth, Dr. Gyawali, and Dr. Goodman joined forces and, with the backing of a philanthropist who had experience as a patient with cancer, convened an organizing committee of more than 30 like-minded oncologists and patient advocates from across the globe.

The group convened for a 3-day “meeting of the minds” in Kingston in April and laid out their intentions in a position paper published online in The Lancet Oncology.

The publication marks the official launch of an ambitious, multipronged, global initiative to enact change: Common Sense Oncology, a new patient-centered movement in cancer care.

In their paper, the committee outline the vision for Common Sense Oncology. The mission: prioritize patient-centered and equitable care by focusing on treatments that improve survival and quality of life, communication that promotes informed decision-making, and systems that ensure access to all patients.

However, increasingly, the cancer community faces a “troubling paradox,” the team wrote in The Lancet. In some instance, treatments that bring minimal benefit are overused while those that can make a meaningful difference in patients’ lives are not accessible to most worldwide.

One reason for this shift: Commercial interests, rather than patient interests, appear to be driving cancer research and care. The team explained, for instance, that over the past few decades, clinical trials have largely pivoted from publicly funded efforts to industry funded ones “designed to achieve regulatory approval or commercial advantage, [often] at the expense of investigating new approaches to surgery, radiotherapy, palliative care, and prevention.”

But “patients deserve better,” the group wrote.

The team outlined three pillars for the initiative: evidence generation, evidence interpretation, and evidence communication.

The evidence generation pillar will aim to improve trial design and reporting to prioritize outcomes that matter to patients.

“One concern is that over the last 10 years or so, most of our new treatments have had very, very small benefits, and we think the bar has dropped too low,” Dr. Booth said, explaining that many trials have moved away from focusing on improving survival and quality of life and toward detecting small differences between treatments on other endpoints – namely progression-free survival. “Those small benefits need to be balanced against the very real risks to our patients.”

The evidence interpretation pillar will aim to foster critical thinking so that clinicians can better identify poorly designed or reported trials and help patients make more informed decisions.

Lastly, the evidence communication pillar will focus on fostering better communication about treatment options among patients, the public, and policymakers. Without clear and thoughtful communication, patients may have unrealistic expectations about the effectiveness of treatments that offer only marginal clinical benefits.

The team also emphasized a need to focus on improving global equity and access to affordable treatments so all patients can benefit from care that extends survival or quality of life.

It’s an ambitious undertaking, especially for a group of full-time clinicians, researchers, and patient advocates “volunteering their time for societal good,” said Dr. Gyawali, but the project teams intend to hit the ground running.

The team has established short-term targets, such as identifying deficiencies in data interpretation within education programs within 6 months and developing educational materials that begin to correct those deficiencies within 12 months, Dr. Booth explained. In the longer term, the team will also aim to design clinical trials that focus on patient outcomes, such as overall survival and quality of life.

Breast cancer survivor and patient advocate Michelle Tregear, PhD, who was recruited to help with Common Sense Oncology, also hopes the initiative will lead to better regulatory control that requires trial sponsors to “focus on what matters to patients, not on surrogate endpoints.”

When it comes to clinical trials, “more, more, more is not always better,” said Dr. Tregear, director of Education and Training Programs for patient advocates at the National Breast Cancer Coalition, Washington, D.C. “Industry interests are not always aligned with patient interests,” and “the system, by and large, is not addressing questions that really matter to patients and their families.”

Although “it’s a tall order to change the direction that we’re going in,” Dr. Tregear is up to the challenge of helping raise awareness, which will hopefully spur patients to demand change.

When Dr. Goodman announced the Common Sense Oncology initiative on Twitter, the news brought excitement, with many oncologists asking to join.

With its sweeping, ambitious goals, the Common Sense Oncology initiative has a long road ahead. Figuring out how to implement some of its aims in practice will take time, Dr. Booth acknowledges, and the initial launch marks the first steps, which will continue to evolve over time.

“We’re not proposing we have all the answers or that we know what every patient would want – we’re saying we’ve not done a good job of communicating to patients the relative benefits and risks of different treatments,” Dr. Booth explained. “We want to celebrate and promote what helps and speak out about what’s not in the best interest of patients.”

Dr. Goodman reported consulting fees from Seattle Genetics and speaking honoraria from Curio. Dr. Booth, Dr. Gyawali, and Dr. Tregear reported having no financial conflicts of interest.

A version of this article appeared on Medscape.com.

Topline

Even 2 days off from radiotherapy for triple-negative breast cancer (TNBC) may affect overall survival.

Methodology

• Clinicians sometimes give women with TNBC a break between radiation sessions so that their skin can heal.
• To gauge the impact, investigators reviewed data from the National Cancer Database on 35,845 patients with TNBC who were treated between 2010 and 2014.
• The researchers determined the number of interrupted radiation treatment days as the difference between the number of days women received radiotherapy versus the number of expected treatment days.
• The team then correlated treatment interruptions with overall survival.

Takeaway

• Longer duration of treatment was associated with worse overall survival (hazard ratio, 1.023).
• Compared with no days or just 1 day off, 2-5 interrupted days (HR, 1.069), 6-10 interrupted days (HR, 1.239), and 11-15 interrupted days (HR, 1.265) increased the likelihood of death in a stepwise fashion.
• More days between diagnosis and first cancer treatment of any kind (HR, 1.001) were associated with worse overall survival.
• Older age (HR, 1.014), Black race (HR, 1.278), race than other Black or White (HR, 1.337), grade II or III/IV tumors (HR, 1.471 and 1.743, respectively), and clinical N1-N3 stage (HR, 2.534, 3.729, 4.992, respectively) were also associated with worse overall survival.

In practice

“All reasonable efforts should be made to prevent any treatment interruptions,” including “prophylactic measures to reduce the severity of radiation dermatitis,” and consideration should be given to the use of hypofractionated regimens to shorten radiation schedules.

Source

The study was led by Ronald Chow, MS, of the Memorial Sloan Kettering Cancer Center, New York, and was published  in the Journal of the National Cancer Institute.

Limitations

• The findings may not be applicable to less aggressive forms of breast cancer.
• Treatment interruptions may have been caused by poor performance status and other confounders that shorten survival.

Disclosures

The study was funded by the National Cancer Institute. The investigators had no disclosures.

A version of this article appeared on Medscape.com.

Topline

Even 2 days off from radiotherapy for triple-negative breast cancer (TNBC) may affect overall survival.

Methodology

• Clinicians sometimes give women with TNBC a break between radiation sessions so that their skin can heal.
• To gauge the impact, investigators reviewed data from the National Cancer Database on 35,845 patients with TNBC who were treated between 2010 and 2014.
• The researchers determined the number of interrupted radiation treatment days as the difference between the number of days women received radiotherapy versus the number of expected treatment days.
• The team then correlated treatment interruptions with overall survival.

Takeaway

• Longer duration of treatment was associated with worse overall survival (hazard ratio, 1.023).
• Compared with no days or just 1 day off, 2-5 interrupted days (HR, 1.069), 6-10 interrupted days (HR, 1.239), and 11-15 interrupted days (HR, 1.265) increased the likelihood of death in a stepwise fashion.
• More days between diagnosis and first cancer treatment of any kind (HR, 1.001) were associated with worse overall survival.
• Older age (HR, 1.014), Black race (HR, 1.278), race than other Black or White (HR, 1.337), grade II or III/IV tumors (HR, 1.471 and 1.743, respectively), and clinical N1-N3 stage (HR, 2.534, 3.729, 4.992, respectively) were also associated with worse overall survival.

In practice

“All reasonable efforts should be made to prevent any treatment interruptions,” including “prophylactic measures to reduce the severity of radiation dermatitis,” and consideration should be given to the use of hypofractionated regimens to shorten radiation schedules.

Source

The study was led by Ronald Chow, MS, of the Memorial Sloan Kettering Cancer Center, New York, and was published  in the Journal of the National Cancer Institute.

Limitations

• The findings may not be applicable to less aggressive forms of breast cancer.
• Treatment interruptions may have been caused by poor performance status and other confounders that shorten survival.

Disclosures

The study was funded by the National Cancer Institute. The investigators had no disclosures.

A version of this article appeared on Medscape.com.

Topline

Even 2 days off from radiotherapy for triple-negative breast cancer (TNBC) may affect overall survival.

Methodology

• Clinicians sometimes give women with TNBC a break between radiation sessions so that their skin can heal.
• To gauge the impact, investigators reviewed data from the National Cancer Database on 35,845 patients with TNBC who were treated between 2010 and 2014.
• The researchers determined the number of interrupted radiation treatment days as the difference between the number of days women received radiotherapy versus the number of expected treatment days.
• The team then correlated treatment interruptions with overall survival.

Takeaway

• Longer duration of treatment was associated with worse overall survival (hazard ratio, 1.023).
• Compared with no days or just 1 day off, 2-5 interrupted days (HR, 1.069), 6-10 interrupted days (HR, 1.239), and 11-15 interrupted days (HR, 1.265) increased the likelihood of death in a stepwise fashion.
• More days between diagnosis and first cancer treatment of any kind (HR, 1.001) were associated with worse overall survival.
• Older age (HR, 1.014), Black race (HR, 1.278), race than other Black or White (HR, 1.337), grade II or III/IV tumors (HR, 1.471 and 1.743, respectively), and clinical N1-N3 stage (HR, 2.534, 3.729, 4.992, respectively) were also associated with worse overall survival.

In practice

“All reasonable efforts should be made to prevent any treatment interruptions,” including “prophylactic measures to reduce the severity of radiation dermatitis,” and consideration should be given to the use of hypofractionated regimens to shorten radiation schedules.

Source

The study was led by Ronald Chow, MS, of the Memorial Sloan Kettering Cancer Center, New York, and was published  in the Journal of the National Cancer Institute.

Limitations

• The findings may not be applicable to less aggressive forms of breast cancer.
• Treatment interruptions may have been caused by poor performance status and other confounders that shorten survival.

Disclosures

The study was funded by the National Cancer Institute. The investigators had no disclosures.

A version of this article appeared on Medscape.com.

Topline

Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.

Methodology

• Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
• Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
• Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
• General fatigue trajectories were classified as low, moderate, high, or decreasing.

Takeaways

• In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
• About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
• Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
• Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.

In practice

“Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered,” the authors concluded.
 

Source

The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
 

Limitations

About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
 

Disclosures

The study had no commercial funding. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Topline

Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.

Methodology

• Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
• Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
• Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
• General fatigue trajectories were classified as low, moderate, high, or decreasing.

Takeaways

• In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
• About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
• Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
• Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.

In practice

“Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered,” the authors concluded.
 

Source

The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
 

Limitations

About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
 

Disclosures

The study had no commercial funding. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Topline

Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.

Methodology

• Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
• Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
• Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
• General fatigue trajectories were classified as low, moderate, high, or decreasing.

Takeaways

• In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
• About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
• Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
• Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.

In practice

“Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered,” the authors concluded.
 

Source

The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
 

Limitations

About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
 

Disclosures

The study had no commercial funding. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early-stage breast cancer who do not adhere to adjuvant endocrine therapy as prescribed or stop early may face as much as a twofold higher risk of relapse or death, a new systematic review found.

METHODOLOGY:

• The investigators conducted a systematic literature search of five databases, looking for studies involving patients with nonmetastatic hormone receptor–positive breast cancer that were published between 2010 and 2020.
• Adequate adherence was defined as a medical possession ratio – the percentage of days the prescribed treatment dose of adjuvant endocrine therapy was available to the patient – of at least 80%.
• Medication nonpersistence was defined as a period in which no new adjuvant endocrine therapy prescriptions were filled before the scheduled end of treatment of 90-180 days, depending on the study.
• The impact of both parameters on event-free survival, which included breast cancer recurrence, disease-free survival, breast cancer–specific survival, and overall survival cancer was calculated.
• Of 2,026 articles retrieved, 14 studies, with sample sizes ranging from 857 to 30,573 patients, met the eligibility and quality criteria; 11 examined patient adherence, and 6 examined patient persistence.

TAKEAWAY:

• Of 10 studies that assessed event-free survival, 7 showed significantly worse survival for nonadherent or nonpersistent patients, at hazard ratios of 1.39-2.44.
• Of nine studies that examined overall survival, seven demonstrated a significantly higher risk for mortality in the groups with nonadherence and nonpersistence, at HRs of 1.26-2.18.
• The largest study, which included data on more than 30,000 patients in Taiwan, found that nonadherence and nonpersistence were associated with a significantly increased risk for mortality, at HRs of 1.98 and 2.18, respectively.

IN PRACTICE:

“The available data highlight the dangers of nonadherence and nonpersistence, showing an up to twofold higher risk of relapse or death for patients who do not use endocrine treatment as prescribed,” the researchers said. “Importantly, improving adherence and persistence represents a low-hanging fruit for increasing survival in luminal breast cancer.”

SOURCE:

The study, led by Finn Magnus Eliassen, MD, department of surgery, Stavanger (Norway) University Hospital, was published online on July 4 in BMC Cancer.

LIMITATIONS:

• The review is limited by the relatively small number of studies that met the eligibility criteria and by their heterogeneity, which ruled out a meta-analysis.
• There are no gold-standard definitions of adherence and persistence.

DISCLOSURES:

• No funding was declared. No relevant financial relationships were declared.
• A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with early-stage breast cancer who do not adhere to adjuvant endocrine therapy as prescribed or stop early may face as much as a twofold higher risk of relapse or death, a new systematic review found.

METHODOLOGY:

• The investigators conducted a systematic literature search of five databases, looking for studies involving patients with nonmetastatic hormone receptor–positive breast cancer that were published between 2010 and 2020.
• Adequate adherence was defined as a medical possession ratio – the percentage of days the prescribed treatment dose of adjuvant endocrine therapy was available to the patient – of at least 80%.
• Medication nonpersistence was defined as a period in which no new adjuvant endocrine therapy prescriptions were filled before the scheduled end of treatment of 90-180 days, depending on the study.
• The impact of both parameters on event-free survival, which included breast cancer recurrence, disease-free survival, breast cancer–specific survival, and overall survival cancer was calculated.
• Of 2,026 articles retrieved, 14 studies, with sample sizes ranging from 857 to 30,573 patients, met the eligibility and quality criteria; 11 examined patient adherence, and 6 examined patient persistence.

TAKEAWAY:

• Of 10 studies that assessed event-free survival, 7 showed significantly worse survival for nonadherent or nonpersistent patients, at hazard ratios of 1.39-2.44.
• Of nine studies that examined overall survival, seven demonstrated a significantly higher risk for mortality in the groups with nonadherence and nonpersistence, at HRs of 1.26-2.18.
• The largest study, which included data on more than 30,000 patients in Taiwan, found that nonadherence and nonpersistence were associated with a significantly increased risk for mortality, at HRs of 1.98 and 2.18, respectively.

IN PRACTICE:

“The available data highlight the dangers of nonadherence and nonpersistence, showing an up to twofold higher risk of relapse or death for patients who do not use endocrine treatment as prescribed,” the researchers said. “Importantly, improving adherence and persistence represents a low-hanging fruit for increasing survival in luminal breast cancer.”

SOURCE:

The study, led by Finn Magnus Eliassen, MD, department of surgery, Stavanger (Norway) University Hospital, was published online on July 4 in BMC Cancer.

LIMITATIONS:

• The review is limited by the relatively small number of studies that met the eligibility criteria and by their heterogeneity, which ruled out a meta-analysis.
• There are no gold-standard definitions of adherence and persistence.

DISCLOSURES:

• No funding was declared. No relevant financial relationships were declared.
• A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with early-stage breast cancer who do not adhere to adjuvant endocrine therapy as prescribed or stop early may face as much as a twofold higher risk of relapse or death, a new systematic review found.

METHODOLOGY:

• The investigators conducted a systematic literature search of five databases, looking for studies involving patients with nonmetastatic hormone receptor–positive breast cancer that were published between 2010 and 2020.
• Adequate adherence was defined as a medical possession ratio – the percentage of days the prescribed treatment dose of adjuvant endocrine therapy was available to the patient – of at least 80%.
• Medication nonpersistence was defined as a period in which no new adjuvant endocrine therapy prescriptions were filled before the scheduled end of treatment of 90-180 days, depending on the study.
• The impact of both parameters on event-free survival, which included breast cancer recurrence, disease-free survival, breast cancer–specific survival, and overall survival cancer was calculated.
• Of 2,026 articles retrieved, 14 studies, with sample sizes ranging from 857 to 30,573 patients, met the eligibility and quality criteria; 11 examined patient adherence, and 6 examined patient persistence.

TAKEAWAY:

• Of 10 studies that assessed event-free survival, 7 showed significantly worse survival for nonadherent or nonpersistent patients, at hazard ratios of 1.39-2.44.
• Of nine studies that examined overall survival, seven demonstrated a significantly higher risk for mortality in the groups with nonadherence and nonpersistence, at HRs of 1.26-2.18.
• The largest study, which included data on more than 30,000 patients in Taiwan, found that nonadherence and nonpersistence were associated with a significantly increased risk for mortality, at HRs of 1.98 and 2.18, respectively.

IN PRACTICE:

“The available data highlight the dangers of nonadherence and nonpersistence, showing an up to twofold higher risk of relapse or death for patients who do not use endocrine treatment as prescribed,” the researchers said. “Importantly, improving adherence and persistence represents a low-hanging fruit for increasing survival in luminal breast cancer.”

SOURCE:

The study, led by Finn Magnus Eliassen, MD, department of surgery, Stavanger (Norway) University Hospital, was published online on July 4 in BMC Cancer.

LIMITATIONS:

• The review is limited by the relatively small number of studies that met the eligibility criteria and by their heterogeneity, which ruled out a meta-analysis.
• There are no gold-standard definitions of adherence and persistence.

DISCLOSURES:

• No funding was declared. No relevant financial relationships were declared.
• A version of this article first appeared on Medscape.com.

The current standard for breast cancer screening (for non–high-risk patients) is an annual or semiannual mammogram for women aged 40 and older.¹ However, mammography-based screening can give false-positive or false-negative results. This can lead to excessive use of invasive tissue biopsies and unnecessary exposure to ionizing radiation—which can also become expensive and time-consuming for patients.²

Both normal and cancerous cells shed cell-free DNA (cfDNA) into the blood circulation.³ Circulating tumor DNA (ctDNA) are fragments of DNA derived from tumor cells that circulate in the blood together with cfDNA. The ctDNA originates directly from a tumor or from circulating tumor cells (and carries information from the tumor cell genome), whereas cfDNA enters the bloodstream after apoptosis or necrosis and carries genome-wide DNA information. The amount of ctDNA in the blood has been shown to be elevated in patients with cancer.³ Different cancers release varying levels of ctDNA; the amount of ctDNA released depends on the number of tumor cells that are in senescence vs undergoing apoptosis.⁴ 

The possibility of incorporating this biomarker obtained from a “liquid biopsy” is currently being studied and will hopefully become a standard of care for breast cancer screening and monitoring. The liquid biopsy detects ctDNA that has been released into the bloodstream from tumor regions and helps identify intratumoral heterogeneity and clonal        evolution.⁵ Additionally, sequencing tumor DNA has opened new possibilities for precision oncology.⁶ Detection of somatic gene mutations, amplifications, and gene fusions helps to deliver targeted therapies.⁶ Analysis of potential somatic mutations in ctDNA, in combination with cfDNA levels, can help capture clinically relevant information beyond single genetic alterations and tumor fraction, potentially improving the accuracy of early detection and screening for breast cancer.

Recent advances in ctDNA testing technology have made it more accurate and reliable. ctDNA testing has several benefits, including early detection of cancer (detecting ctDNA at low levels⁾⁷; monitoring of tumor dynamics, therapeutic response, and residual disease⁸; as well as analysis of the evolution of genetic or epigenetic alterations characterizing the tumor.⁹ Its noninvasiveness, rapidity, and low cost allow for longitudinal monitoring of cancer in real time, potentially capturing tumor heterogeneity.^10,11 

The liquid biopsy potentially can give more options for therapeutic monitoring for breast cancer and may mirror clinically relevant genetic alterations that occur in all tumor tissues. Liquid biopsy offers many advantages. It allows for the detection of minimal residual disease and micrometastatic disease that may be difficult to detect with a traditional tissue biopsy.¹² Liquid biopsy detects ctDNA that has been released into the bloodstream from multiple tumor regions and allows the possibility of identifying intratumoral heterogeneity and  clonal evolution.⁵ It can also detect small quantitative variations within the blood, enabling real-time surveillance.

The liquid biopsy can offer earlier and easier access to some tumor-based genetic information at any given timepoint and can replace a tumor tissue biopsy in some cases, helping to avoid delays and complications of a solid tumor invasive biopsy procedure. This is especially relevant in the metastatic setting, in which ctDNA might be the only available genetic material from tumors.¹³ Tissue biopsy can only provide a static and spatially limited view of the disease at the time of sampling; ctDNA analysis could potentially reflect the genetic alterations that occur in all metastatic breast cancer sites over time.^14,15 Furthermore, machine learning of multi-gene signatures, obtained from ctDNA, can possibly identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to direct tumor tissue DNA or RNA profiling.¹⁶

ctDNA testing is currently being studied to monitor patients who have been diagnosed with breast cancer. Small retrospective studies have shown that detection of ctDNA in plasma, after patients have completed therapy for early-stage breast cancer, is associated with a very high risk of relapse.¹⁷

Ongoing studies are examining the tailoring of adjuvant treatment based on ctDNA. If these trials are successful, certain aspects of adjuvant treatment could be lessened, or omitted, for patients who have undetectable ctDNA or intensified for patients who have detectable ctDNA after definitive treatments. This could personalize treatment specifically to the patient.

The detection and persistence of ctDNA in the middle of neoadjuvant systemic therapy may have the potential to negatively predict response to treatment and identify patients who will not achieve pathologic complete response. This may have the potential to aid in clinical decision-making for treatment escalation in these nonresponders.¹⁸ 

Despite these distinct characteristics, the low levels of ctDNA found in early-stage disease, along with the lack of ctDNA shedding from some tumors, can further complicate or impede detection of recurrence in early-stage breast cancer. Testing is further complicated by hematologic genetic alterations.⁵ The limitation of ctDNA approaches is that these techniques only detect known mutations in certain genes, so patients without these mutations could be overlooked, limiting the application of this technology.¹⁹

Overall, ctDNA testing represents a promising area of research for the diagnosis, treatment, and monitoring of breast cancer. While more research is needed to fully understand its potential, the advances in this technology are certainly exciting and could lead to significant improvements in patient outcomes. It is hopeful that in the near future, ctDNA testing from liquid biopsy could become a standard of care in breast cancer screening, ultimately helping clinicians to personalize treatment therapies and improve patient outcomes when treating patients with breast cancer.

The current standard for breast cancer screening (for non–high-risk patients) is an annual or semiannual mammogram for women aged 40 and older.¹ However, mammography-based screening can give false-positive or false-negative results. This can lead to excessive use of invasive tissue biopsies and unnecessary exposure to ionizing radiation—which can also become expensive and time-consuming for patients.²

Both normal and cancerous cells shed cell-free DNA (cfDNA) into the blood circulation.³ Circulating tumor DNA (ctDNA) are fragments of DNA derived from tumor cells that circulate in the blood together with cfDNA. The ctDNA originates directly from a tumor or from circulating tumor cells (and carries information from the tumor cell genome), whereas cfDNA enters the bloodstream after apoptosis or necrosis and carries genome-wide DNA information. The amount of ctDNA in the blood has been shown to be elevated in patients with cancer.³ Different cancers release varying levels of ctDNA; the amount of ctDNA released depends on the number of tumor cells that are in senescence vs undergoing apoptosis.⁴ 

The possibility of incorporating this biomarker obtained from a “liquid biopsy” is currently being studied and will hopefully become a standard of care for breast cancer screening and monitoring. The liquid biopsy detects ctDNA that has been released into the bloodstream from tumor regions and helps identify intratumoral heterogeneity and clonal        evolution.⁵ Additionally, sequencing tumor DNA has opened new possibilities for precision oncology.⁶ Detection of somatic gene mutations, amplifications, and gene fusions helps to deliver targeted therapies.⁶ Analysis of potential somatic mutations in ctDNA, in combination with cfDNA levels, can help capture clinically relevant information beyond single genetic alterations and tumor fraction, potentially improving the accuracy of early detection and screening for breast cancer.

Recent advances in ctDNA testing technology have made it more accurate and reliable. ctDNA testing has several benefits, including early detection of cancer (detecting ctDNA at low levels⁾⁷; monitoring of tumor dynamics, therapeutic response, and residual disease⁸; as well as analysis of the evolution of genetic or epigenetic alterations characterizing the tumor.⁹ Its noninvasiveness, rapidity, and low cost allow for longitudinal monitoring of cancer in real time, potentially capturing tumor heterogeneity.^10,11 

The liquid biopsy potentially can give more options for therapeutic monitoring for breast cancer and may mirror clinically relevant genetic alterations that occur in all tumor tissues. Liquid biopsy offers many advantages. It allows for the detection of minimal residual disease and micrometastatic disease that may be difficult to detect with a traditional tissue biopsy.¹² Liquid biopsy detects ctDNA that has been released into the bloodstream from multiple tumor regions and allows the possibility of identifying intratumoral heterogeneity and  clonal evolution.⁵ It can also detect small quantitative variations within the blood, enabling real-time surveillance.

The liquid biopsy can offer earlier and easier access to some tumor-based genetic information at any given timepoint and can replace a tumor tissue biopsy in some cases, helping to avoid delays and complications of a solid tumor invasive biopsy procedure. This is especially relevant in the metastatic setting, in which ctDNA might be the only available genetic material from tumors.¹³ Tissue biopsy can only provide a static and spatially limited view of the disease at the time of sampling; ctDNA analysis could potentially reflect the genetic alterations that occur in all metastatic breast cancer sites over time.^14,15 Furthermore, machine learning of multi-gene signatures, obtained from ctDNA, can possibly identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to direct tumor tissue DNA or RNA profiling.¹⁶

ctDNA testing is currently being studied to monitor patients who have been diagnosed with breast cancer. Small retrospective studies have shown that detection of ctDNA in plasma, after patients have completed therapy for early-stage breast cancer, is associated with a very high risk of relapse.¹⁷

Ongoing studies are examining the tailoring of adjuvant treatment based on ctDNA. If these trials are successful, certain aspects of adjuvant treatment could be lessened, or omitted, for patients who have undetectable ctDNA or intensified for patients who have detectable ctDNA after definitive treatments. This could personalize treatment specifically to the patient.

The detection and persistence of ctDNA in the middle of neoadjuvant systemic therapy may have the potential to negatively predict response to treatment and identify patients who will not achieve pathologic complete response. This may have the potential to aid in clinical decision-making for treatment escalation in these nonresponders.¹⁸ 

Despite these distinct characteristics, the low levels of ctDNA found in early-stage disease, along with the lack of ctDNA shedding from some tumors, can further complicate or impede detection of recurrence in early-stage breast cancer. Testing is further complicated by hematologic genetic alterations.⁵ The limitation of ctDNA approaches is that these techniques only detect known mutations in certain genes, so patients without these mutations could be overlooked, limiting the application of this technology.¹⁹

Overall, ctDNA testing represents a promising area of research for the diagnosis, treatment, and monitoring of breast cancer. While more research is needed to fully understand its potential, the advances in this technology are certainly exciting and could lead to significant improvements in patient outcomes. It is hopeful that in the near future, ctDNA testing from liquid biopsy could become a standard of care in breast cancer screening, ultimately helping clinicians to personalize treatment therapies and improve patient outcomes when treating patients with breast cancer.

The current standard for breast cancer screening (for non–high-risk patients) is an annual or semiannual mammogram for women aged 40 and older.¹ However, mammography-based screening can give false-positive or false-negative results. This can lead to excessive use of invasive tissue biopsies and unnecessary exposure to ionizing radiation—which can also become expensive and time-consuming for patients.²

Both normal and cancerous cells shed cell-free DNA (cfDNA) into the blood circulation.³ Circulating tumor DNA (ctDNA) are fragments of DNA derived from tumor cells that circulate in the blood together with cfDNA. The ctDNA originates directly from a tumor or from circulating tumor cells (and carries information from the tumor cell genome), whereas cfDNA enters the bloodstream after apoptosis or necrosis and carries genome-wide DNA information. The amount of ctDNA in the blood has been shown to be elevated in patients with cancer.³ Different cancers release varying levels of ctDNA; the amount of ctDNA released depends on the number of tumor cells that are in senescence vs undergoing apoptosis.⁴ 

The possibility of incorporating this biomarker obtained from a “liquid biopsy” is currently being studied and will hopefully become a standard of care for breast cancer screening and monitoring. The liquid biopsy detects ctDNA that has been released into the bloodstream from tumor regions and helps identify intratumoral heterogeneity and clonal        evolution.⁵ Additionally, sequencing tumor DNA has opened new possibilities for precision oncology.⁶ Detection of somatic gene mutations, amplifications, and gene fusions helps to deliver targeted therapies.⁶ Analysis of potential somatic mutations in ctDNA, in combination with cfDNA levels, can help capture clinically relevant information beyond single genetic alterations and tumor fraction, potentially improving the accuracy of early detection and screening for breast cancer.

Recent advances in ctDNA testing technology have made it more accurate and reliable. ctDNA testing has several benefits, including early detection of cancer (detecting ctDNA at low levels⁾⁷; monitoring of tumor dynamics, therapeutic response, and residual disease⁸; as well as analysis of the evolution of genetic or epigenetic alterations characterizing the tumor.⁹ Its noninvasiveness, rapidity, and low cost allow for longitudinal monitoring of cancer in real time, potentially capturing tumor heterogeneity.^10,11 

The liquid biopsy potentially can give more options for therapeutic monitoring for breast cancer and may mirror clinically relevant genetic alterations that occur in all tumor tissues. Liquid biopsy offers many advantages. It allows for the detection of minimal residual disease and micrometastatic disease that may be difficult to detect with a traditional tissue biopsy.¹² Liquid biopsy detects ctDNA that has been released into the bloodstream from multiple tumor regions and allows the possibility of identifying intratumoral heterogeneity and  clonal evolution.⁵ It can also detect small quantitative variations within the blood, enabling real-time surveillance.

The liquid biopsy can offer earlier and easier access to some tumor-based genetic information at any given timepoint and can replace a tumor tissue biopsy in some cases, helping to avoid delays and complications of a solid tumor invasive biopsy procedure. This is especially relevant in the metastatic setting, in which ctDNA might be the only available genetic material from tumors.¹³ Tissue biopsy can only provide a static and spatially limited view of the disease at the time of sampling; ctDNA analysis could potentially reflect the genetic alterations that occur in all metastatic breast cancer sites over time.^14,15 Furthermore, machine learning of multi-gene signatures, obtained from ctDNA, can possibly identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to direct tumor tissue DNA or RNA profiling.¹⁶

ctDNA testing is currently being studied to monitor patients who have been diagnosed with breast cancer. Small retrospective studies have shown that detection of ctDNA in plasma, after patients have completed therapy for early-stage breast cancer, is associated with a very high risk of relapse.¹⁷

Ongoing studies are examining the tailoring of adjuvant treatment based on ctDNA. If these trials are successful, certain aspects of adjuvant treatment could be lessened, or omitted, for patients who have undetectable ctDNA or intensified for patients who have detectable ctDNA after definitive treatments. This could personalize treatment specifically to the patient.

The detection and persistence of ctDNA in the middle of neoadjuvant systemic therapy may have the potential to negatively predict response to treatment and identify patients who will not achieve pathologic complete response. This may have the potential to aid in clinical decision-making for treatment escalation in these nonresponders.¹⁸ 

Despite these distinct characteristics, the low levels of ctDNA found in early-stage disease, along with the lack of ctDNA shedding from some tumors, can further complicate or impede detection of recurrence in early-stage breast cancer. Testing is further complicated by hematologic genetic alterations.⁵ The limitation of ctDNA approaches is that these techniques only detect known mutations in certain genes, so patients without these mutations could be overlooked, limiting the application of this technology.¹⁹

Overall, ctDNA testing represents a promising area of research for the diagnosis, treatment, and monitoring of breast cancer. While more research is needed to fully understand its potential, the advances in this technology are certainly exciting and could lead to significant improvements in patient outcomes. It is hopeful that in the near future, ctDNA testing from liquid biopsy could become a standard of care in breast cancer screening, ultimately helping clinicians to personalize treatment therapies and improve patient outcomes when treating patients with breast cancer.

Click here to view more from Cancer Data Trends 2023.

Click here to view more from Cancer Data Trends 2023.

Click here to view more from Cancer Data Trends 2023.

Federal Practitioner and the Association of VA Hematology/Oncology (AVAHO) present the 2023 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• COVID-19 Outcomes in Veterans With Hematologic Cancers
• Promising New Approaches for Testicular and Prostate Cancer
• Screening Guideline Updates and New Treatments in Colon Cancer
• Exposure-Related Cancers: A Look at the PACT Act
• New Classifications and Emerging Treatments in Brain Cancer
• Gender Disparity in Breast Cancer Among US Veterans
• Lung Cancer Screening in Veterans
• Necessary Updates to Skin Cancer Risk Stratification
• Innovation in Cancer Treatment

Federal Practitioner and the Association of VA Hematology/Oncology (AVAHO) present the 2023 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• COVID-19 Outcomes in Veterans With Hematologic Cancers
• Promising New Approaches for Testicular and Prostate Cancer
• Screening Guideline Updates and New Treatments in Colon Cancer
• Exposure-Related Cancers: A Look at the PACT Act
• New Classifications and Emerging Treatments in Brain Cancer
• Gender Disparity in Breast Cancer Among US Veterans
• Lung Cancer Screening in Veterans
• Necessary Updates to Skin Cancer Risk Stratification
• Innovation in Cancer Treatment

Federal Practitioner and the Association of VA Hematology/Oncology (AVAHO) present the 2023 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• COVID-19 Outcomes in Veterans With Hematologic Cancers
• Promising New Approaches for Testicular and Prostate Cancer
• Screening Guideline Updates and New Treatments in Colon Cancer
• Exposure-Related Cancers: A Look at the PACT Act
• New Classifications and Emerging Treatments in Brain Cancer
• Gender Disparity in Breast Cancer Among US Veterans
• Lung Cancer Screening in Veterans
• Necessary Updates to Skin Cancer Risk Stratification
• Innovation in Cancer Treatment