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This is how you get patients back for follow-up cancer testing
according to authors of a new study published in the Journal of the American Medical Association.
Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.
Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.
“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.
Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.
“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.
In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.
Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.
They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.
All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.
The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.
All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.
After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.
Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.
The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.
“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.
While interventions improved patient follow-up, the overall rates were still low.
“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.
The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.
The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
according to authors of a new study published in the Journal of the American Medical Association.
Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.
Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.
“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.
Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.
“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.
In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.
Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.
They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.
All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.
The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.
All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.
After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.
Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.
The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.
“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.
While interventions improved patient follow-up, the overall rates were still low.
“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.
The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.
The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
according to authors of a new study published in the Journal of the American Medical Association.
Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.
Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.
“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.
Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.
“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.
In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.
Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.
They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.
All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.
The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.
All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.
After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.
Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.
The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.
“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.
While interventions improved patient follow-up, the overall rates were still low.
“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.
The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.
The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM JAMA
Does surgery improve survival in metastatic breast cancer?
TOPLINE:
METHODOLOGY:
- Given conflicting results from prospective trials and improved outcomes reported in retrospective studies, removing the primary tumor in patients with metastatic breast cancer remains common practice but also “controversial,” the authors explained.
- To clarify whether to remove the primary tumor in metastatic breast cancer, investigators performed a meta-analysis of the five randomized clinical trials evaluating the issue.
- The five trials, published from 2015 to 2023, included 1,381 women with de novo metastatic breast cancer; half had their primary tumor removed, half did not.
TAKEAWAY:
- The analysis revealed no overall survival benefit for patients who underwent surgical excision of their primary breast tumor (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.76-1.14).
- Surgery was not associated with an overall survival benefit in subgroup analyses by receptor status, pattern of metastasis (bone vs. viscera or oligometastatic vs nonoligometastatic disease), number of metastatic sites, or location of metastatic lesions.
- The one possible exception: Surgery did appear to improve overall survival in younger, premenopausal women (HR, 0.74; 95% CI 0.58-0.94), but “the lack of uniform definitions and inconsistent trial results suggest that this subgroup analysis should be viewed as exploratory and requiring further validation,” the authors said.
- Breast surgery was associated with improved local progression-free survival (HR, 0.37) but not distant progression-free survival or patient-reported quality of life.
IN PRACTICE:
“We conclude that surgical excision of the primary tumor in case of de novo metastatic breast cancer is not associated with improved patient survival,” with a “potential exception” among younger patients, the authors said. “As such, besides the need to palliate local symptoms, surgery should not be routinely offered to patients with metastatic disease.”
SOURCE:
The work, led by Guillermo Villacampa of the SOLTI Breast Cancer Research Group in Barcelona, was published Sept. 12 in The Oncologist.
LIMITATIONS:
The five trials had various weaknesses, including imbalances in patient characteristics, protocol violations regarding planned and administered treatment, and missing information on associations between surgical margins and outcomes.
DISCLOSURES:
There was no funding for the work. Investigators reported speaker fees, consultant fees, and/or research funding from various companies, including Merck, AstraZeneca, Pfizer, and Novartis.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Given conflicting results from prospective trials and improved outcomes reported in retrospective studies, removing the primary tumor in patients with metastatic breast cancer remains common practice but also “controversial,” the authors explained.
- To clarify whether to remove the primary tumor in metastatic breast cancer, investigators performed a meta-analysis of the five randomized clinical trials evaluating the issue.
- The five trials, published from 2015 to 2023, included 1,381 women with de novo metastatic breast cancer; half had their primary tumor removed, half did not.
TAKEAWAY:
- The analysis revealed no overall survival benefit for patients who underwent surgical excision of their primary breast tumor (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.76-1.14).
- Surgery was not associated with an overall survival benefit in subgroup analyses by receptor status, pattern of metastasis (bone vs. viscera or oligometastatic vs nonoligometastatic disease), number of metastatic sites, or location of metastatic lesions.
- The one possible exception: Surgery did appear to improve overall survival in younger, premenopausal women (HR, 0.74; 95% CI 0.58-0.94), but “the lack of uniform definitions and inconsistent trial results suggest that this subgroup analysis should be viewed as exploratory and requiring further validation,” the authors said.
- Breast surgery was associated with improved local progression-free survival (HR, 0.37) but not distant progression-free survival or patient-reported quality of life.
IN PRACTICE:
“We conclude that surgical excision of the primary tumor in case of de novo metastatic breast cancer is not associated with improved patient survival,” with a “potential exception” among younger patients, the authors said. “As such, besides the need to palliate local symptoms, surgery should not be routinely offered to patients with metastatic disease.”
SOURCE:
The work, led by Guillermo Villacampa of the SOLTI Breast Cancer Research Group in Barcelona, was published Sept. 12 in The Oncologist.
LIMITATIONS:
The five trials had various weaknesses, including imbalances in patient characteristics, protocol violations regarding planned and administered treatment, and missing information on associations between surgical margins and outcomes.
DISCLOSURES:
There was no funding for the work. Investigators reported speaker fees, consultant fees, and/or research funding from various companies, including Merck, AstraZeneca, Pfizer, and Novartis.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Given conflicting results from prospective trials and improved outcomes reported in retrospective studies, removing the primary tumor in patients with metastatic breast cancer remains common practice but also “controversial,” the authors explained.
- To clarify whether to remove the primary tumor in metastatic breast cancer, investigators performed a meta-analysis of the five randomized clinical trials evaluating the issue.
- The five trials, published from 2015 to 2023, included 1,381 women with de novo metastatic breast cancer; half had their primary tumor removed, half did not.
TAKEAWAY:
- The analysis revealed no overall survival benefit for patients who underwent surgical excision of their primary breast tumor (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.76-1.14).
- Surgery was not associated with an overall survival benefit in subgroup analyses by receptor status, pattern of metastasis (bone vs. viscera or oligometastatic vs nonoligometastatic disease), number of metastatic sites, or location of metastatic lesions.
- The one possible exception: Surgery did appear to improve overall survival in younger, premenopausal women (HR, 0.74; 95% CI 0.58-0.94), but “the lack of uniform definitions and inconsistent trial results suggest that this subgroup analysis should be viewed as exploratory and requiring further validation,” the authors said.
- Breast surgery was associated with improved local progression-free survival (HR, 0.37) but not distant progression-free survival or patient-reported quality of life.
IN PRACTICE:
“We conclude that surgical excision of the primary tumor in case of de novo metastatic breast cancer is not associated with improved patient survival,” with a “potential exception” among younger patients, the authors said. “As such, besides the need to palliate local symptoms, surgery should not be routinely offered to patients with metastatic disease.”
SOURCE:
The work, led by Guillermo Villacampa of the SOLTI Breast Cancer Research Group in Barcelona, was published Sept. 12 in The Oncologist.
LIMITATIONS:
The five trials had various weaknesses, including imbalances in patient characteristics, protocol violations regarding planned and administered treatment, and missing information on associations between surgical margins and outcomes.
DISCLOSURES:
There was no funding for the work. Investigators reported speaker fees, consultant fees, and/or research funding from various companies, including Merck, AstraZeneca, Pfizer, and Novartis.
A version of this article first appeared on Medscape.com.
‘Reassuring’ follow-up validates radiation strategy for early breast cancer
SAN DIEGO –
The follow-up analysis of the 2,016-subject IMPORT LOW study found that 10-year overall survival rates were 87.8% (95% confidence interval, 84.9-90.1) for a full-breast radiation group, 87.2% (95% CI, 84.3-89.6) for a reduced-dose group, and 90.3% (95% CI, 87.7-92.4) in a partial-breast group. Breast cancer radiotherapy specialist Anna Kirby, MB, MD (Res), MA, of the Royal Marsden and Institute of Cancer Research, London, reported the results at the annual meeting of the American Society for Radiation Oncology.
Ipsilateral breast tumor relapse was also similar in the three groups at the 10-year mark at 2.8% (95% CI, 1.8-4.5), 1.9% (95% CI, 1.1-3.4), and 2.8% (95% CI, 1.7-4.5), respectively. Moderate/marked adverse effects were deemed to be low.
Dr. Kirby said the new findings are not “practice-changing.” However, “this complementary data supporting the change in practice that happened in the UK and elsewhere following the publication back in 2017.”
The findings are “reassuring,” breast cancer radiology specialist Robert W. Mutter, MD, of the Mayo Clinic, Rochester, Minn., said in an interview after reviewing the study findings. While the outcomes and adverse events are similar between the groups, “partial-breast irradiation is attractive because it exposes less normal tissue such as the heart and lungs than whole-breast irradiation. This could lead to fewer side effects for patients later in life at a population level. Partial-breast irradiation should be considered a standard of care in selected patients.”
In a presentation at ASTRO, Dr. Kirby provided background about the motivation for the study. It was clear that radiotherapy reduces local recurrence by up to two-thirds in early breast cancer, she said. “But in a population with excellent prognosis, this translates into relatively small absolute benefits from radiotherapy for many of our lower-risk patients,” she said. “All patients treated are at risk of radiotherapy side effects, and these become the main hazard for many women. Radiotherapy that’s focused on the part of the breast that contained the tumor – the so-called tumor bed – may reduce the long-term complications from radiotherapy, particularly in the breast, and potentially in the heart and lung, whilst hopefully maintaining low local recurrence rates.”
The initial 5-year study was a randomized, multicenter, phase III trial of patients ≥ age 50 in the United Kingdom who were tracked since recruitment in 2007-2010 (median age, 63). All had undergone breast conservation surgery. The patients were assigned to the control group (n = 674, 40 Gy), reduced-dose (n = 673, 40 Gy) and partial-breast (n = 669, 40 Gy to partial breast only) in 15 daily treatment fractions. The initial results, published in The Lancet, reported noninferiority for both reduced-dose and partial-breast radiotherapy. Adverse effects were similar in the three groups except for change in breast appearance, which was better in partial-breast therapy vs. whole-breast, and breast harder or firmer, which was better in both partial- and reduced-dose groups vs. whole-breast.
Dr. Mutter described the IMPORT LOW trial as “a practice-changing study.”
The trial was unique since both the whole-breast and partial-breast arms received the same dosing schedule, he said, which “enables an unbiased assessment of the impact of target volume on treatment outcomes.” This contrasts “with other partial-breast irradiation studies where a different dosing schedule was employed for whole-breast and partial-breast irradiation.”
The new analysis tracked patients for a median of 121 months. “There is no difference in local recurrence rate across the three arms,” Dr. Kirby said. There were no differences in overall survival, breast cancer or cardiac deaths, she added, and “neither was there any difference in the time to any moderate or marked clinician-assessed breast normal tissue endpoint.”
Heart and lung outcomes may improve over time in the lower-dose groups because of less radiation exposure, “but we haven’t shown that yet with this data set.”
Dr. Mutter cautioned that “the results of this trial may not necessarily be extrapolated to other partial-breast irradiation techniques that treat a much smaller volume of breast tissue such as intracavitary brachytherapy and intraoperative radiotherapy. Whether these same excellent outcomes can be achieved with smaller treatment volumes is an area for further investigation.”
Funding information was not provided; the initial study was funded by Cancer Research UK. Dr. Kirby discloses travel costs paid by European Society of Radiotherapy and Oncology, and other authors have various disclosures including relationships with companies such as Pfizer, Seagen, AstraZeneca, Eli Lilly, Bayer, and Janssen. Dr. Mutter has no disclosures.
SAN DIEGO –
The follow-up analysis of the 2,016-subject IMPORT LOW study found that 10-year overall survival rates were 87.8% (95% confidence interval, 84.9-90.1) for a full-breast radiation group, 87.2% (95% CI, 84.3-89.6) for a reduced-dose group, and 90.3% (95% CI, 87.7-92.4) in a partial-breast group. Breast cancer radiotherapy specialist Anna Kirby, MB, MD (Res), MA, of the Royal Marsden and Institute of Cancer Research, London, reported the results at the annual meeting of the American Society for Radiation Oncology.
Ipsilateral breast tumor relapse was also similar in the three groups at the 10-year mark at 2.8% (95% CI, 1.8-4.5), 1.9% (95% CI, 1.1-3.4), and 2.8% (95% CI, 1.7-4.5), respectively. Moderate/marked adverse effects were deemed to be low.
Dr. Kirby said the new findings are not “practice-changing.” However, “this complementary data supporting the change in practice that happened in the UK and elsewhere following the publication back in 2017.”
The findings are “reassuring,” breast cancer radiology specialist Robert W. Mutter, MD, of the Mayo Clinic, Rochester, Minn., said in an interview after reviewing the study findings. While the outcomes and adverse events are similar between the groups, “partial-breast irradiation is attractive because it exposes less normal tissue such as the heart and lungs than whole-breast irradiation. This could lead to fewer side effects for patients later in life at a population level. Partial-breast irradiation should be considered a standard of care in selected patients.”
In a presentation at ASTRO, Dr. Kirby provided background about the motivation for the study. It was clear that radiotherapy reduces local recurrence by up to two-thirds in early breast cancer, she said. “But in a population with excellent prognosis, this translates into relatively small absolute benefits from radiotherapy for many of our lower-risk patients,” she said. “All patients treated are at risk of radiotherapy side effects, and these become the main hazard for many women. Radiotherapy that’s focused on the part of the breast that contained the tumor – the so-called tumor bed – may reduce the long-term complications from radiotherapy, particularly in the breast, and potentially in the heart and lung, whilst hopefully maintaining low local recurrence rates.”
The initial 5-year study was a randomized, multicenter, phase III trial of patients ≥ age 50 in the United Kingdom who were tracked since recruitment in 2007-2010 (median age, 63). All had undergone breast conservation surgery. The patients were assigned to the control group (n = 674, 40 Gy), reduced-dose (n = 673, 40 Gy) and partial-breast (n = 669, 40 Gy to partial breast only) in 15 daily treatment fractions. The initial results, published in The Lancet, reported noninferiority for both reduced-dose and partial-breast radiotherapy. Adverse effects were similar in the three groups except for change in breast appearance, which was better in partial-breast therapy vs. whole-breast, and breast harder or firmer, which was better in both partial- and reduced-dose groups vs. whole-breast.
Dr. Mutter described the IMPORT LOW trial as “a practice-changing study.”
The trial was unique since both the whole-breast and partial-breast arms received the same dosing schedule, he said, which “enables an unbiased assessment of the impact of target volume on treatment outcomes.” This contrasts “with other partial-breast irradiation studies where a different dosing schedule was employed for whole-breast and partial-breast irradiation.”
The new analysis tracked patients for a median of 121 months. “There is no difference in local recurrence rate across the three arms,” Dr. Kirby said. There were no differences in overall survival, breast cancer or cardiac deaths, she added, and “neither was there any difference in the time to any moderate or marked clinician-assessed breast normal tissue endpoint.”
Heart and lung outcomes may improve over time in the lower-dose groups because of less radiation exposure, “but we haven’t shown that yet with this data set.”
Dr. Mutter cautioned that “the results of this trial may not necessarily be extrapolated to other partial-breast irradiation techniques that treat a much smaller volume of breast tissue such as intracavitary brachytherapy and intraoperative radiotherapy. Whether these same excellent outcomes can be achieved with smaller treatment volumes is an area for further investigation.”
Funding information was not provided; the initial study was funded by Cancer Research UK. Dr. Kirby discloses travel costs paid by European Society of Radiotherapy and Oncology, and other authors have various disclosures including relationships with companies such as Pfizer, Seagen, AstraZeneca, Eli Lilly, Bayer, and Janssen. Dr. Mutter has no disclosures.
SAN DIEGO –
The follow-up analysis of the 2,016-subject IMPORT LOW study found that 10-year overall survival rates were 87.8% (95% confidence interval, 84.9-90.1) for a full-breast radiation group, 87.2% (95% CI, 84.3-89.6) for a reduced-dose group, and 90.3% (95% CI, 87.7-92.4) in a partial-breast group. Breast cancer radiotherapy specialist Anna Kirby, MB, MD (Res), MA, of the Royal Marsden and Institute of Cancer Research, London, reported the results at the annual meeting of the American Society for Radiation Oncology.
Ipsilateral breast tumor relapse was also similar in the three groups at the 10-year mark at 2.8% (95% CI, 1.8-4.5), 1.9% (95% CI, 1.1-3.4), and 2.8% (95% CI, 1.7-4.5), respectively. Moderate/marked adverse effects were deemed to be low.
Dr. Kirby said the new findings are not “practice-changing.” However, “this complementary data supporting the change in practice that happened in the UK and elsewhere following the publication back in 2017.”
The findings are “reassuring,” breast cancer radiology specialist Robert W. Mutter, MD, of the Mayo Clinic, Rochester, Minn., said in an interview after reviewing the study findings. While the outcomes and adverse events are similar between the groups, “partial-breast irradiation is attractive because it exposes less normal tissue such as the heart and lungs than whole-breast irradiation. This could lead to fewer side effects for patients later in life at a population level. Partial-breast irradiation should be considered a standard of care in selected patients.”
In a presentation at ASTRO, Dr. Kirby provided background about the motivation for the study. It was clear that radiotherapy reduces local recurrence by up to two-thirds in early breast cancer, she said. “But in a population with excellent prognosis, this translates into relatively small absolute benefits from radiotherapy for many of our lower-risk patients,” she said. “All patients treated are at risk of radiotherapy side effects, and these become the main hazard for many women. Radiotherapy that’s focused on the part of the breast that contained the tumor – the so-called tumor bed – may reduce the long-term complications from radiotherapy, particularly in the breast, and potentially in the heart and lung, whilst hopefully maintaining low local recurrence rates.”
The initial 5-year study was a randomized, multicenter, phase III trial of patients ≥ age 50 in the United Kingdom who were tracked since recruitment in 2007-2010 (median age, 63). All had undergone breast conservation surgery. The patients were assigned to the control group (n = 674, 40 Gy), reduced-dose (n = 673, 40 Gy) and partial-breast (n = 669, 40 Gy to partial breast only) in 15 daily treatment fractions. The initial results, published in The Lancet, reported noninferiority for both reduced-dose and partial-breast radiotherapy. Adverse effects were similar in the three groups except for change in breast appearance, which was better in partial-breast therapy vs. whole-breast, and breast harder or firmer, which was better in both partial- and reduced-dose groups vs. whole-breast.
Dr. Mutter described the IMPORT LOW trial as “a practice-changing study.”
The trial was unique since both the whole-breast and partial-breast arms received the same dosing schedule, he said, which “enables an unbiased assessment of the impact of target volume on treatment outcomes.” This contrasts “with other partial-breast irradiation studies where a different dosing schedule was employed for whole-breast and partial-breast irradiation.”
The new analysis tracked patients for a median of 121 months. “There is no difference in local recurrence rate across the three arms,” Dr. Kirby said. There were no differences in overall survival, breast cancer or cardiac deaths, she added, and “neither was there any difference in the time to any moderate or marked clinician-assessed breast normal tissue endpoint.”
Heart and lung outcomes may improve over time in the lower-dose groups because of less radiation exposure, “but we haven’t shown that yet with this data set.”
Dr. Mutter cautioned that “the results of this trial may not necessarily be extrapolated to other partial-breast irradiation techniques that treat a much smaller volume of breast tissue such as intracavitary brachytherapy and intraoperative radiotherapy. Whether these same excellent outcomes can be achieved with smaller treatment volumes is an area for further investigation.”
Funding information was not provided; the initial study was funded by Cancer Research UK. Dr. Kirby discloses travel costs paid by European Society of Radiotherapy and Oncology, and other authors have various disclosures including relationships with companies such as Pfizer, Seagen, AstraZeneca, Eli Lilly, Bayer, and Janssen. Dr. Mutter has no disclosures.
AT ASTRO 2023
Adopting high-dose radiation vs. conventional after mastectomy could be ‘game changer’
SAN DIEGO – , according to a new prospective, randomized study.
Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.
The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”
According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”
The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.
From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.
The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).
The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.
“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.
Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).
Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).
The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.
At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”
The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.
“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.
In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”
However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.
The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.
SAN DIEGO – , according to a new prospective, randomized study.
Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.
The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”
According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”
The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.
From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.
The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).
The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.
“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.
Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).
Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).
The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.
At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”
The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.
“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.
In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”
However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.
The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.
SAN DIEGO – , according to a new prospective, randomized study.
Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.
The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”
According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”
The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.
From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.
The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).
The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.
“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.
Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).
Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).
The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.
At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”
The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.
“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.
In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”
However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.
The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.
AT ASTRO 2023
SABR could defer systemic therapy in oligoprogressive breast cancer
SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.
In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.
“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”
According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.
The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.
For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).
The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.
The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.
Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”
Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.
A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.
The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.
In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”
Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.
The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.
SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.
In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.
“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”
According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.
The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.
For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).
The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.
The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.
Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”
Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.
A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.
The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.
In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”
Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.
The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.
SAN DIEGO – Stereotactic ablative body radiotherapy (SABR) appeared to delay the need for changes in systemic therapy in postmenopausal patients with oligoprogressive luminal ER-positive, HER2-negative breast cancer, according to a new phase 2 study.
In the AVATAR trial, patients with one to five metastatic lesions who’d been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and aromatase inhibitors for at least 6 months underwent SABR. Of those, 47% had event-free survival of more than 6 months, an unexpectedly high figure, reported radiation oncologist Steven David, MBBS, of Peter MacCallum Cancer Center, Melbourne, and colleagues at the annual meeting of the American Society for Radiation Oncology.
“We found surprisingly that SABR delayed a change in therapy by 10 months, which is great for patients. Also, one in three patients had a second round of SABR,” said Dr. David in an interview. “This trial provides the first prospective evidence to delay a change in therapy in this population, and this strategy is ready to go now.”
According to Dr. David, oligoprogressive luminal, ER-positive, HER2-negative, advanced breast cancer cannot be cured. However, patients can live more than 10 years in some cases, and an early treatment – CDK 4/6 inhibitors and aromatase inhibitors – is well tolerated. “Patients can lead a normal life and avoid chemo” as long as those medications keep working.
The goal of the study was to determine if SABR is helpful in these patients. The treatment, which produces highly focused radiation, “has very few side effects and does a great job in eliminating progressing metastases,” Dr. David said.
For the study, researchers recruited 32 subjects at 13 Australian sites. Participants could not have had leptomeningeal disease, previous chemotherapy for metastatic disease, or prior radiotherapy to an oligoprogressing lesion. Most metastases were to bone (n = 44, 71%), node (systemic, n = 8; 13%) and lung (n = 4; 6%).
The patients were treated with SABR, most commonly 24 Gy (n = 25; 43%) and 20 Gy (n = 10; 17%); half had one lesion treated (50%), and 25% had two lesions treated.
The median follow-up was 15.8 months. The median event-free survival was 5.2 months (95% confidence interval, 3.1-9.4 months), with events defined as progression within 6 months or in at least three lesions. Fifteen patients (47%) reached event-free survival of 6 or more months.
Elysia Donovan, MD, MSc, a radiation oncologist at McMaster University, Hamilton, Ont., said in an interview that the new study is thoughtfully designed, although it’s not definitive. “At this point we still do not know the optimal treatment regimen for oligoprogressive breast cancer. The findings of this trial are promising and exciting. However, further randomized trials are required before routine implementation in clinical practice. For now, patients should be considered in a case by case basis with multidisciplinary discussion to determine the optimal systemic therapy regimen at oligoprogression and whether SABR may provide benefit.”
Median modified progression-free survival was 10.4 months, and median progression-free survival was 5.2 months; 31% of patients received SABR for further oligoprogression, and 46% patients remained on CDK4/6 inhibitors and aromatase inhibitors for 12 months. Overall survival was 100%.
A total of 14 patients had grade 1 adverse events, 2 had grade 2 events, and none had grade 3 or higher events; 47% had no treatment-related toxicity.
The strategy “potentially has a place in other cancer types and other breast cancer types,” Dr. David said.
In an interview, Katarzyna Jerzak, MD, MSc, a medical oncologist with Sunnybrook Odette Cancer Center in Toronto, said the findings are promising, although the study is small and the patients are similar. Toxicity was limited, and a 12-month delay in a switch to therapy – reached by 46% – “is very meaningful for patients.” She added that “the positive results should serve as motivation to investigate the strategy further.”
Dr. David said a larger trial called AVATAR 2 is funded and in the works. It will have more patients and more breast cancer subtypes.
The study was funded by the Donald Ratcliffe and Phyllis McLeod Trust. Dr. David disclosed grant/research funding from Roche Genentech, and other authors reported various disclosures including relationships with AstraZeneca, Pfizer, Gilead, and others. Dr. Jerzak disclosed speaker/advisor board/consultant relationships with Amgen, AstraZeneca, Apobiologix, Eli Lilly, Esai, Genomic Health, Gilead, Knight Therapeutics, Merck, Myriad Genetics, Pfizer, Roche, Seagen, and Novartis and research funding from AstraZeneca, Eli Lilly, and Seagen. Dr. Donovan disclosed a Bright Foundation grant for a prospective trial of SABR for oligoprogressive breast cancer.
AT ASTRO 2023
USPSTF should reconsider recommendation to lower mammogram age: Experts
The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.
The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.
Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”
But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.
In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.
Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.
Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.
That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”
In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.
Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.
The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.
Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.
The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
Ease or exacerbate racial disparity?
Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.
Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.
“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.
Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.
“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”
Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.
In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
Reconsider the change?
Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.
“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.
That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”
The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”
The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.
The research had no funding. Dr. Woloshin has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.
The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.
Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”
But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.
In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.
Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.
Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.
That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”
In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.
Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.
The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.
Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.
The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
Ease or exacerbate racial disparity?
Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.
Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.
“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.
Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.
“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”
Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.
In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
Reconsider the change?
Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.
“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.
That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”
The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”
The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.
The research had no funding. Dr. Woloshin has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.
The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.
Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”
But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.
In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.
Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.
Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.
That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”
In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.
Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.
The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.
Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.
The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
Ease or exacerbate racial disparity?
Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.
Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.
“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.
Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.
“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”
Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.
In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
Reconsider the change?
Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.
“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.
That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”
The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”
The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.
The research had no funding. Dr. Woloshin has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Commentary: Radiation therapy, endocrine therapy, metformin, and statins in breast cancer, October 2023
Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.2 In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.3 These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.
Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.4 A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.
Additional References
- Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586
- Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X
- Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
- Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797
Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.2 In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.3 These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.
Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.4 A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.
Additional References
- Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586
- Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X
- Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
- Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797
Endocrine therapy (ET) remains the backbone of treatment for hormone receptor–positive breast cancer; however, 15%-20% of tumors are initially resistant to ET and endocrine resistance develops over time in approximately 30%-40%.2 In an effort to overcome limitations with historical standard-of-care endocrine agents, the class of oral potent selective estrogen receptor degraders (SERD) is evolving. The phase 2, randomized, controlled coopERA Breast Cancer trial evaluated the antiproliferative effect of giredestrant (a highly potent nonsteroidal oral SERD) compared with anastrozole (each combined with palbociclib after 2-week window-of-opportunity phase) among postmenopausal women with early-stage (cT1c-cT4) ER+/HER2- breast cancer with a Ki67 score ≥ 5% (Hurvitz et al). Among 221 enrolled patients (giredestrant group n = 112, and anastrozole group n = 109), giredestrant led to a significantly greater relative geometric mean reduction of Ki67 at 2 weeks from baseline compared with anastrozole (-75% vs -67%; P = 0.043). Neutropenia (26% and 27%) and decreased neutrophil count (15% and 15%) were the most common grade 3-4 adverse events in the giredestrant-palbociclib and anastrozole-palbociclib groups, respectively. The value of Ki67 as a biomarker for efficacy and outcome was demonstrated in the phase 3 POETIC trial, which showed that the degree of Ki67 reduction after 2 weeks of ET correlated with 5-year recurrence risk.3 These data encourage further investigation of oral SERD combinations, predictors of response, and long-term outcomes that may influence agent selection and sequencing.
Anticancer properties have been demonstrated with aspirin, statins, and metformin, although the data on the prognostic impact of these agents in breast cancer have shown mixed results.4 A nationwide population-based cohort study including 26,190 women aged 50 years or older diagnosed with breast cancer and surviving 12 months or more after diagnosis was performed to evaluate the postdiagnosis use of aspirin, statins, and metformin and association with breast cancer-specific survival (BCSS) (Löfling et al). At 6.1 years of follow-up, there were 2169 deaths related to breast cancer and the results supported an association of postdiagnostic use of statins and metformin with survival (hazard ratio for association between use of statins vs no use and BCSS was 0.84 [95% CI 0.75-0.94]; hazard ratio for association between metformin use vs use of nonmetformin antidiabetics and BCSS was 0.70 [95% CI 0.51-0.96]). Furthermore, there appeared to be differences in association by ER status. An important relationship exists between cardiovascular health and breast cancer, and future efforts should continue to study pharmacologic and lifestyle interventions that may optimize metabolic profiles and improve outcomes for patients.
Additional References
- Kunkler IH, Williams LJ, Jack WJL, et al. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585-594. doi: 10.1056/NEJMoa2207586
- Lei JT, Anurag M, Haricharan S, et al. Endocrine therapy resistance: New insights. Breast. 2019;48:S26-S30. doi: 10.1016/S0960-9776(19)31118-X
- Smith I, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): An open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020;21:1443-1454. doi: 10.1016/S1470-2045(20)30458-7
- Nowakowska MK, Lei X, Thompson MT, et al. Association of statin use with clinical outcomes in patients with triple-negative breast cancer. Cancer. 2021;127:4142-4150. doi: 10.1002/cncr.33797
Commentary: New treatments and trial results, October 2023
A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.
It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.
Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.
The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.
Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.1 Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.
Additional Reference
- Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266
A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.
It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.
Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.
The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.
Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.1 Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.
Additional Reference
- Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266
A recently published study by Rugo and colleagues presented the final analysis of overall survival and endpoints by trophoblast cell surface antigen 2 (Trop-2) expression. Results showed that at the 12.5-month median follow-up, sacituzumab govitecan vs chemotherapy improved overall survival by 3.2 months (hazard ratio 0.79; P = .020). The survival benefit was consistent across different levels of Trop-2 expression. No new adverse events were reported; however, one fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. These updated data continue to support the use of sacituzumab govitecan as a new treatment option for patients with endocrine-resistant HR+ and HER2- MBC.
It remains unclear whether anti-HER2 therapy alone (without chemotherapy) is an effective treatment approach for patients with ERBB2-positive MBC in the first-line setting. Huober and the Swiss Group for Clinical Cancer Research, the Unicancer Breast Group, and the Dutch Breast Cancer Research Group report a phase 2 trial that included 210 patients with ERBB2+ MBC who were randomly assigned to receive pertuzumab plus trastuzumab with or without chemotherapy followed by trastuzumab-emtansine as the second-line therapy in both groups. Despite worse progression-free survival in the nonchemotherapy vs the chemotherapy group (8.4 months [95% CI 7.9-12.0] vs 23.3 months [95% CI 18.9-33.1]), overall survival rates were comparable at 2 years of follow-up (79.0% [90% CI 71.4%-85.4%] vs 78.1% [90% CI 70.4%-84.5%]). Furthermore, adverse events were more frequent in the chemotherapy cohort, with small quality-of-life improvements from baseline in the nonchemotherapy cohort. Further prospective data are needed to confirm whether a chemotherapy-free approach is an acceptable treatment approach in certain population of patients, without unfavorable effects on overall survival.
Prior results from the SOFT and TEXT trials have shown improved survival with the addition of ovarian function suppression (OFS) in premenopausal women after chemotherapy. The ASTRRA trial is a similar phase 3 study that included 1282 premenopausal women with estrogen receptor–positive BC who remained premenopausal or regained ovarian function after chemotherapy and were randomly assigned to receive tamoxifen with or without OFS. The results showed a consistent disease-free survival benefit in women who received tamoxifen plus OFS vs tamoxifen alone (85.4% vs 80.2%; hazard ratio 0.67; P = .003) after a median follow-up of 8 years. There were no significant differences in 8-year OS rates between the two groups (P = .305), although both cohorts had high OS rates overall (> 95%). This trial highlights the overall excellent prognosis in this patient population and underscores the importance of OFS in the subgroup of patients who remain in a premenopausal state or resume ovarian function after chemotherapy.
The ICE study (Ibandronate with or without Capecitabine in Elderly patients with early breast cancer) was a phase 3 trial looking at 1358 patients age ≥ 65 years with node-positive or high-risk node-negative early BC who were randomly assigned to receive 2 years of ibandronate with or without capecitabine for six cycles in the adjuvant setting. At a median follow-up of 61 months, the 5-year invasive disease-free survival rates were similar amongst patients treated with adjuvant ibandronate plus capecitabine and ibandronate alone (hazard ratio 0.96; 95% CI 0.78-1.19). Outcomes were independent of age, nodal status, and hormone receptor status. The incidences of high-grade gastrointestinal disorders (6.7% vs 1.0%; P < .001) and skin toxicity (14.6% vs 0.6%; P < .01) were significantly higher in the capecitabine plus ibandronate arm vs the ibandronate alone arm.
Adjuvant capecitabine plus ibandronate failed to show improved survival outcomes compared with ibandronate alone in older patients with node-positive/high-risk node-negative BC. This was similar to results of the CALGB 49907 trial, which showed inferior survival for adjuvant capecitabine compared with standard adjuvant chemotherapy in patients ≥ 65 years of age.1 Therefore, although oral capecitabine may be more tolerable than intravenous polychemotherapy in older patients with high-risk BC, this should be weighed against lower efficacy.
Additional Reference
- Muss HB, Berry DA, Cirrincione CT, et al, for the CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009;360:2055-2065. doi: 10.1056/NEJMoa0810266
It’s safe to skip SLNB for small, ultrasound-negative breast cancer
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.
The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?
A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.
In short, European
At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.
Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.
The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.
Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
A case-by-case decision
The study included women of all ages, with a median age of 60 years.
Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.
The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.
Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.
However, it didn’t seem to make a difference in the overall study results.
Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).
Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.
“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.
The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.
Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.
The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.
The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?
A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.
In short, European
At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.
Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.
The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.
Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
A case-by-case decision
The study included women of all ages, with a median age of 60 years.
Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.
The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.
Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.
However, it didn’t seem to make a difference in the overall study results.
Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).
Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.
“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.
The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.
Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.
The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging in early breast cancer, but previous studies have shown that removal of axillary lymph nodes has no therapeutic effect.
The finding raises a question: Is SLNB even necessary when preoperative axillary imaging is negative?
A new randomized trial addresses the question and brings much “welcome clarity” to the issue, Seema Khan, MD, a surgical oncologist and breast cancer researcher at Northwestern University, Chicago, said in an editorial to the trial, both of which were published in JAMA Oncology.
In short, European
At a median of follow-up of 5.7 years, distant disease-free survival and other outcomes were essentially equivalent between 708 women randomized to SLNB followed by full axillary dissection if nodes are positive and 697 other women randomized to observation without SLNB.
Adjuvant therapies were not significantly different between the two groups largely because adjuvant decisions were driven by tumor characteristics, not axillary studies.
The results support “the argument that sentinel node positivity is not, in and of itself, a critical parameter that determines therapeutic plans and outcomes in patients with stage I breast cancer. This is a major accomplishment of the SOUND [Sentinel Node vs. Observation After Axillary Ultra-Sound] trial, which will be strengthened when longer-term data become available” at 10-year follow up, Dr. Khan said.
Investigators led by Oreste Davide Gentilini, MD, a breast cancer surgeon at San Raffaele Scientific and Research Hospital, Milan, estimated that, of the 2.3 million breast cancers diagnosed globally each year, the study suggests “that approximately 500,000 patients might be able to take advantage of the total omission of axillary surgery,” sparing women lymphedema and other serious side effects and saving health care systems substantial dollars.
A case-by-case decision
The study included women of all ages, with a median age of 60 years.
Subjects had a single tumor 0.8-1.5 cm across with negative preoperative axillary ultrasonography. Almost 90% had estrogen receptor ERBB2 (formerly HER2) positive tumors. Almost all of the subjects had radiotherapy, and about 20% of women in each arm also had chemotherapy.
The trial was conducted in 18 sites, most in Italy with other sites in Switzerland, Spain, and Chile.
Overall, 13.7% of women in the SLNB group turned out to have positive axillary nodes, with 0.6% having four or more positive nodes.
However, it didn’t seem to make a difference in the overall study results.
Five-year distant disease-free survival was 97.7% in the SLNB group and 98% in the observation arm (P for noninferiority = .02).
Secondary outcomes were also essentially identical, including local/regional relapse (1.7% with SLNB versus 1.6% without); distant metastases (1.8% vs. 2%), and death from breast cancer (1% vs. 0.6%). The cumulative incidence of axillary lymph node recurrences in the observation arm was just 0.4%.
“These findings suggest that patients with BC of a diameter equal to or smaller than 2 cm and a negative result on preoperative axillary lymph node ultrasonography can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan,” Dr. Gentilini and associates concluded.
The team cautioned that decision to forgo SLNB must be made on a case-by-case basis in a multidisciplinary setting because there are still situations where nodal pathology is relevant, for instance when deciding to add chemotherapy to endocrine treatments in premenopausal women with endocrine-responsive disease.
Only about 20% of the subjects were under 50 years old and the team didn’t break down their results by age, which makes it difficult to apply their results to the situation.
The work was funded by the European Institute of Oncology. Dr. Khan didn’t have any disclosures. Dr. Gentilini reported personal fees from AstraZeneca, Bayer, BD, Eli Lilly, and MSD. Two other investigators also reported personal fees from those and/or other companies.
FROM JAMA ONCOLOGY
Older women who get mammograms risk overdiagnosis
TOPLINE:
Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.
METHODOLOGY:
- Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain.
- To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
- The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
- Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women.
- Results were adjusted for potential confounders, including age, race, and ethnicity.
TAKEAWAY:
- Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
- Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
- Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
- The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.
IN PRACTICE:
The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”
SOURCE:
The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.
LIMITATIONS:
The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.
DISCLOSURES:
The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
TOPLINE:
Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.
METHODOLOGY:
- Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain.
- To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
- The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
- Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women.
- Results were adjusted for potential confounders, including age, race, and ethnicity.
TAKEAWAY:
- Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
- Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
- Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
- The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.
IN PRACTICE:
The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”
SOURCE:
The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.
LIMITATIONS:
The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.
DISCLOSURES:
The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
TOPLINE:
Women who continue breast cancer screening after age 70 face a considerable risk for overdiagnosis.
METHODOLOGY:
- Overdiagnosis – the risk of detecting and treating cancers that would never have caused issues in a person’s lifetime – is increasingly recognized as a harm of breast cancer screening; however, the scope of the problem among older women remains uncertain.
- To get an idea, investigators linked Medicare claims data with Surveillance, Epidemiology, and End Results (SEER) data for 54,635 women 70 years or older to compare the incidence of breast cancer and breast cancer–specific death among women who continued screening mammography with those who did not.
- The women all had undergone recent screening mammograms and had no history of breast cancer at study entry. Those who had a subsequent mammogram within 3 years were classified as undergoing continued screening while those who did not were classified as not undergoing continued screening.
- Overdiagnosis was defined as the difference in cumulative incidence of breast cancer between screened and unscreened women divided by the cumulative incidence among screened women.
- Results were adjusted for potential confounders, including age, race, and ethnicity.
TAKEAWAY:
- Over 80% of women 70-84 years old and more than 60% of women 85 years or older continued screening.
- Among women 70-74 years old, the adjusted cumulative incidence of breast cancer was 6.1 cases per 100 screened women vs. 4.2 cases per 100 unscreened women; for women aged 75-84 years old, the cumulative incidence was 4.9 per 100 screened women vs. 2.6 per 100 unscreened women, and for women 85 years and older, the cumulative incidence was 2.8 vs. 1.3 per 100, respectively.
- Estimates of overdiagnosis ranged from 31% of breast cancer cases among screened women in the 70-74 age group to 54% of cases in the 85 and older group.
- The researchers found no statistically significant reduction in breast cancer–specific death associated with screening in any age or life-expectancy group. Overdiagnosis appeared to be driven by in situ and localized invasive breast cancer, not advanced breast cancer.
IN PRACTICE:
The proportion of older women who continue to receive screening mammograms and may experience breast cancer overdiagnosis is “considerable” and “increases with advancing age and with decreasing life expectancy,” the authors conclude. Given potential benefits and harms of screening in this population, “patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions.”
SOURCE:
The study was led by Ilana Richman, MD, MHS, of the Yale School of Medicine, New Haven, Connecticut, and published in the Annals of Internal Medicine.
LIMITATIONS:
The definition of screening mammography in the study may have misclassified some diagnostic mammograms as screening. Using a more conservative definition of screening mammogram, which largely accounted for this misclassification, estimates for overdiagnosis were smaller, ranging from 15% of cases in the 70-74 age group to 44% of cases in the 85 and older group. Results could not be adjusted for breast density, family history, and other breast cancer risk factors not captured by the data.
DISCLOSURES:
The work was funded by the National Cancer Institute. One author reported funding from Genentech and Johnson & Johnson.
A version of this article first appeared on Medscape.com.