Key clinical point: Although patients with early breast cancer (BC) can undergo immediate breast reconstruction (IBR) after mastectomy, those with invasive BC should be made aware of the possibility of local recurrence (LR) if they have undergone skin- or nipple-sparing mastectomy (SSM/NSM), have not received radiotherapy, or had lymphovascular invasion or cancer at the surgical margin.

Major finding: The rate of 7-year LR was generally low (3.6%) but was higher in invasive vs non-invasive BC (4.3% vs 2.1%; P < .001). SSM/NSM (P < .001), lymphovascular invasion (P = .005), cancer at the surgical margin (P < .001), and no radiotherapy (P = .003) were associated with worse LR rates in invasive BC.

Study details: This retrospective, observational study included 4153 patients with early BC who underwent mastectomy with IBR, of which 2851 and 1272 patients had invasive and non-invasive BC, respectively.

Disclosures: This study was supported by a grant from the scientific committee of the Japanese Breast Cancer Society. The authors declared no conflicts of interest.

Source: Ogiya A et al, on behalf of Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Long-term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases. Ann Surg Oncol. 2023 (Jul 5). Doi: 10.1245/s10434-023-13832-6

Key clinical point: Although patients with early breast cancer (BC) can undergo immediate breast reconstruction (IBR) after mastectomy, those with invasive BC should be made aware of the possibility of local recurrence (LR) if they have undergone skin- or nipple-sparing mastectomy (SSM/NSM), have not received radiotherapy, or had lymphovascular invasion or cancer at the surgical margin.

Major finding: The rate of 7-year LR was generally low (3.6%) but was higher in invasive vs non-invasive BC (4.3% vs 2.1%; P < .001). SSM/NSM (P < .001), lymphovascular invasion (P = .005), cancer at the surgical margin (P < .001), and no radiotherapy (P = .003) were associated with worse LR rates in invasive BC.

Study details: This retrospective, observational study included 4153 patients with early BC who underwent mastectomy with IBR, of which 2851 and 1272 patients had invasive and non-invasive BC, respectively.

Disclosures: This study was supported by a grant from the scientific committee of the Japanese Breast Cancer Society. The authors declared no conflicts of interest.

Source: Ogiya A et al, on behalf of Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Long-term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases. Ann Surg Oncol. 2023 (Jul 5). Doi: 10.1245/s10434-023-13832-6

Key clinical point: Although patients with early breast cancer (BC) can undergo immediate breast reconstruction (IBR) after mastectomy, those with invasive BC should be made aware of the possibility of local recurrence (LR) if they have undergone skin- or nipple-sparing mastectomy (SSM/NSM), have not received radiotherapy, or had lymphovascular invasion or cancer at the surgical margin.

Major finding: The rate of 7-year LR was generally low (3.6%) but was higher in invasive vs non-invasive BC (4.3% vs 2.1%; P < .001). SSM/NSM (P < .001), lymphovascular invasion (P = .005), cancer at the surgical margin (P < .001), and no radiotherapy (P = .003) were associated with worse LR rates in invasive BC.

Study details: This retrospective, observational study included 4153 patients with early BC who underwent mastectomy with IBR, of which 2851 and 1272 patients had invasive and non-invasive BC, respectively.

Disclosures: This study was supported by a grant from the scientific committee of the Japanese Breast Cancer Society. The authors declared no conflicts of interest.

Source: Ogiya A et al, on behalf of Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Long-term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases. Ann Surg Oncol. 2023 (Jul 5). Doi: 10.1245/s10434-023-13832-6

Key clinical point: Invasive lobular carcinoma (ILC), the most common special histological type of breast cancer (BC), had poorer survival outcomes than invasive ductal carcinoma (IDC) and no-lobular special type BC.

Major finding: Patients with ILC vs no-lobular special type BC and IDC had the shortest duration of both disease-free survival (197.2 vs 216.7 and 226.5 months, respectively) and overall survival (209.8 vs 227.9 and 233.2 months, respectively), and ILC vs IDC was associated with significantly worse overall survival (hazard ratio 1.45; P = .045).

Study details: Findings are from a retrospective study including 2157 patients with invasive carcinoma of the breast who were categorized into IDC (n = 1814), ILC (n = 193), and no-lobular special type BC (n = 150).

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Cosar R et al. Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer. PLoS One. 2023;18(7):e0283445 (Jul 10). Doi: 10.1371/journal.pone.0283445

Key clinical point: Invasive lobular carcinoma (ILC), the most common special histological type of breast cancer (BC), had poorer survival outcomes than invasive ductal carcinoma (IDC) and no-lobular special type BC.

Major finding: Patients with ILC vs no-lobular special type BC and IDC had the shortest duration of both disease-free survival (197.2 vs 216.7 and 226.5 months, respectively) and overall survival (209.8 vs 227.9 and 233.2 months, respectively), and ILC vs IDC was associated with significantly worse overall survival (hazard ratio 1.45; P = .045).

Study details: Findings are from a retrospective study including 2157 patients with invasive carcinoma of the breast who were categorized into IDC (n = 1814), ILC (n = 193), and no-lobular special type BC (n = 150).

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Cosar R et al. Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer. PLoS One. 2023;18(7):e0283445 (Jul 10). Doi: 10.1371/journal.pone.0283445

Key clinical point: Invasive lobular carcinoma (ILC), the most common special histological type of breast cancer (BC), had poorer survival outcomes than invasive ductal carcinoma (IDC) and no-lobular special type BC.

Major finding: Patients with ILC vs no-lobular special type BC and IDC had the shortest duration of both disease-free survival (197.2 vs 216.7 and 226.5 months, respectively) and overall survival (209.8 vs 227.9 and 233.2 months, respectively), and ILC vs IDC was associated with significantly worse overall survival (hazard ratio 1.45; P = .045).

Study details: Findings are from a retrospective study including 2157 patients with invasive carcinoma of the breast who were categorized into IDC (n = 1814), ILC (n = 193), and no-lobular special type BC (n = 150).

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Cosar R et al. Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer. PLoS One. 2023;18(7):e0283445 (Jul 10). Doi: 10.1371/journal.pone.0283445

Key clinical point: A higher body mass index (BMI) was not linked directly to survival outcomes but was linked to worse prognostic clinicopathologic variables in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) invasive lobular carcinoma (ILC) of the breast.

Major finding: Although BMI was not directly associated with disease-free survival and overall survival outcomes (both P = .08), a higher BMI was associated with larger tumor size (≥2 cm; P < .001), higher tumor grade (grade 3; P = .014), nodal involvement (P < .001), and multifocal BC (P = .01), which indicated significantly worsened prognosis.

Study details: This multicenter, retrospective study included 2490 patients with ER+/HER2− ILC of the breast, of which 1410, 712, and 368 patients were lean, overweight, and obese, respectively.

Disclosures: This study was funded by the Luxembourg Cancer Foundation and other sources. The authors declared no conflicts of interest.

Source: Baelen KV, Nguyen H-L, et al. Association of body mass index with clinicopathological features and survival in patients with primary invasive lobular breast cancer. Eur J Cancer. 2023;112988 (Jul 12). Doi: 10.1016/j.ejca.2023.112988

Key clinical point: A higher body mass index (BMI) was not linked directly to survival outcomes but was linked to worse prognostic clinicopathologic variables in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) invasive lobular carcinoma (ILC) of the breast.

Major finding: Although BMI was not directly associated with disease-free survival and overall survival outcomes (both P = .08), a higher BMI was associated with larger tumor size (≥2 cm; P < .001), higher tumor grade (grade 3; P = .014), nodal involvement (P < .001), and multifocal BC (P = .01), which indicated significantly worsened prognosis.

Study details: This multicenter, retrospective study included 2490 patients with ER+/HER2− ILC of the breast, of which 1410, 712, and 368 patients were lean, overweight, and obese, respectively.

Disclosures: This study was funded by the Luxembourg Cancer Foundation and other sources. The authors declared no conflicts of interest.

Source: Baelen KV, Nguyen H-L, et al. Association of body mass index with clinicopathological features and survival in patients with primary invasive lobular breast cancer. Eur J Cancer. 2023;112988 (Jul 12). Doi: 10.1016/j.ejca.2023.112988

Key clinical point: A higher body mass index (BMI) was not linked directly to survival outcomes but was linked to worse prognostic clinicopathologic variables in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) invasive lobular carcinoma (ILC) of the breast.

Major finding: Although BMI was not directly associated with disease-free survival and overall survival outcomes (both P = .08), a higher BMI was associated with larger tumor size (≥2 cm; P < .001), higher tumor grade (grade 3; P = .014), nodal involvement (P < .001), and multifocal BC (P = .01), which indicated significantly worsened prognosis.

Study details: This multicenter, retrospective study included 2490 patients with ER+/HER2− ILC of the breast, of which 1410, 712, and 368 patients were lean, overweight, and obese, respectively.

Disclosures: This study was funded by the Luxembourg Cancer Foundation and other sources. The authors declared no conflicts of interest.

Source: Baelen KV, Nguyen H-L, et al. Association of body mass index with clinicopathological features and survival in patients with primary invasive lobular breast cancer. Eur J Cancer. 2023;112988 (Jul 12). Doi: 10.1016/j.ejca.2023.112988

Key clinical point: Adjuvant radiotherapy treatment interruption for a greater number of days was associated with worsened survival outcomes in patients with nonmetastatic triple-negative breast cancer (TNBC).

Major finding: As little as 2-5 days of treatment interruption worsened the overall survival outcomes in patients with TNBC compared with 0-1 day (hazard ratio [HR] 1.069; 95% CI 1.002-1.140), with the mortality risk increasing further in case of 6-10 days (HR 1.236; 95% CI 1.137-1.345) and 11-15 days (HR 1.259; 95% CI 1.112-1.415) of treatment interruption.

Study details: This study analyzed the data of 35,845 patients with nonmetastatic TNBC from the US National Cancer Database who had received external beam radiation therapy and had an overall survival of at least 12 months.

Disclosures: This study was partly funded by the US National Institutes of Health/National Cancer Institute (NIH/NCI) Cancer Center support grant. The authors declared no conflicts of interest.

Source: Chow R et al. Effect of treatment interruptions on overall survival in patients with triple negative breast cancer. J Natl Cancer Inst. 2023 (Jul 3). Doi: 10.1093/jnci/djad127

Key clinical point: Adjuvant radiotherapy treatment interruption for a greater number of days was associated with worsened survival outcomes in patients with nonmetastatic triple-negative breast cancer (TNBC).

Major finding: As little as 2-5 days of treatment interruption worsened the overall survival outcomes in patients with TNBC compared with 0-1 day (hazard ratio [HR] 1.069; 95% CI 1.002-1.140), with the mortality risk increasing further in case of 6-10 days (HR 1.236; 95% CI 1.137-1.345) and 11-15 days (HR 1.259; 95% CI 1.112-1.415) of treatment interruption.

Study details: This study analyzed the data of 35,845 patients with nonmetastatic TNBC from the US National Cancer Database who had received external beam radiation therapy and had an overall survival of at least 12 months.

Disclosures: This study was partly funded by the US National Institutes of Health/National Cancer Institute (NIH/NCI) Cancer Center support grant. The authors declared no conflicts of interest.

Source: Chow R et al. Effect of treatment interruptions on overall survival in patients with triple negative breast cancer. J Natl Cancer Inst. 2023 (Jul 3). Doi: 10.1093/jnci/djad127

Key clinical point: Adjuvant radiotherapy treatment interruption for a greater number of days was associated with worsened survival outcomes in patients with nonmetastatic triple-negative breast cancer (TNBC).

Major finding: As little as 2-5 days of treatment interruption worsened the overall survival outcomes in patients with TNBC compared with 0-1 day (hazard ratio [HR] 1.069; 95% CI 1.002-1.140), with the mortality risk increasing further in case of 6-10 days (HR 1.236; 95% CI 1.137-1.345) and 11-15 days (HR 1.259; 95% CI 1.112-1.415) of treatment interruption.

Study details: This study analyzed the data of 35,845 patients with nonmetastatic TNBC from the US National Cancer Database who had received external beam radiation therapy and had an overall survival of at least 12 months.

Disclosures: This study was partly funded by the US National Institutes of Health/National Cancer Institute (NIH/NCI) Cancer Center support grant. The authors declared no conflicts of interest.

Source: Chow R et al. Effect of treatment interruptions on overall survival in patients with triple negative breast cancer. J Natl Cancer Inst. 2023 (Jul 3). Doi: 10.1093/jnci/djad127

Key clinical point: Female patients with meningioma have approximately 10-fold higher odds of developing breast cancer (BC) and should be screened more often for BC.

Major finding: Compared with the general population, the prevalence of BC was considerably higher in female patients with meningioma (odds ratio 9.87; 95% CI 7.31-13.32).

Study details: Findings are from a meta-analysis of 18 studies including patients diagnosed with intracranial or spinal meningioma or BC or both.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Degeneffe A et al. The association between meningioma and breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2023;6(6):e2318620 (Jun 16). Doi: 10.1001/jamanetworkopen.2023.18620

Key clinical point: Female patients with meningioma have approximately 10-fold higher odds of developing breast cancer (BC) and should be screened more often for BC.

Major finding: Compared with the general population, the prevalence of BC was considerably higher in female patients with meningioma (odds ratio 9.87; 95% CI 7.31-13.32).

Study details: Findings are from a meta-analysis of 18 studies including patients diagnosed with intracranial or spinal meningioma or BC or both.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Degeneffe A et al. The association between meningioma and breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2023;6(6):e2318620 (Jun 16). Doi: 10.1001/jamanetworkopen.2023.18620

Key clinical point: Female patients with meningioma have approximately 10-fold higher odds of developing breast cancer (BC) and should be screened more often for BC.

Major finding: Compared with the general population, the prevalence of BC was considerably higher in female patients with meningioma (odds ratio 9.87; 95% CI 7.31-13.32).

Study details: Findings are from a meta-analysis of 18 studies including patients diagnosed with intracranial or spinal meningioma or BC or both.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Degeneffe A et al. The association between meningioma and breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2023;6(6):e2318620 (Jun 16). Doi: 10.1001/jamanetworkopen.2023.18620

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.

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.