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Breast cancer liquid biopsies don’t change outcomes....yet
LAS VEGAS – Although circulating tumor cells are prognostic in breast cancer, they aren’t likely to become a part of routine practice until they’ve been shown to improve outcomes, and that hasn’t happened yet, according to Anthony Lucci, MD, professor of breast surgical oncology at MD Anderson Cancer Center, Houston.
MD Anderson and other institutions have established that in breast cancer, from baseline through treatment follow-up, the presence of circulating tumor cells (CTCs) in the blood predicts worse outcomes in both metastatic and local disease, even among women who have a pathologic complete response to treatment.
That knowledge has not yet translated into better outcomes. In a pivotal trial, survival was no better in metastatic breast cancer when women were switched to an alternative chemotherapy regimen after their CTC levels did not fall in response to first-line treatment, compared with women who remained on their initial agent despite persistently high CTCs (J Clin Oncol. 2014 Nov 1;32[31]:3483-9).
“When we tried to switch chemotherapy” based on CTCs, “it really didn’t make a difference, so no one is really quite sure yet what to do with this information. We can’t tell a patient that they are likely to have a much worse outcome, but there’s nothing we can do about it,” and “I don’t think payers will pay” for CTC testing in breast cancer until “we establish a predictive benefit, and show what agents will reduce CTCs and improve outcomes,” Dr. Lucci said at the American Society of Breast Surgeons annual meeting.
Even so, the promise of CTCs as a clinical tool is too great to abandon research, and work continues at MD Anderson and elsewhere. It’s thought that tumor cells in the blood aren’t simply a marker of disease, but rather microscopic disease in themselves that contributes to recurrence and progression. It’s possible that cells shed by tumors lie dormant in the bone marrow, then reactivate and reseed the original tumor site or give rise to distant metastases.
CTCs are similar to tumor cells that have been found in the bone marrow of women with apparently quiescent breast cancer, but finding them in the blood means “you don’t have to poke a needle in someone’s bone. You can just take a sample of their blood, and it tells you the same information,” Dr. Lucci said.
CTCs have been shown in breast cancer to rise and fall depending on tumor response. “In the future, I do think we will [use them] as a serial monitoring tool and a guide to therapy.” There might even be a role for breast cancer screening, he said.
Analyzing the blood for evidence of solid tumors – popularly called “liquid biopsy” – has shown benefits in a variety of cancers, particularly for identifying disease, and in some cases mutations, sooner than with conventional methods. Science is catching up to the old-school notion that cancer spreads through the blood.
Another approach is to look for circulating tumor DNA, which has been shown to be useful for early detection in gynecologic cancers. The idea is that a few tumor cells shatter and spill their genetic material into the blood early on. “In the majority of breast cancer patients,” however, “you don’t find actionable mutations” with circulating tumor DNA, especially in earlier-stage, nonmetastatic disease. “There’s not enough DNA released into the blood,” Dr. Lucci said.
But “we need to be monitoring the blood on a routine basis” for breast cancer clues. “That, I think, is the wave of the future. Just looking at x-rays and waiting for something to happen is too late,” he said.
Dr. Lucci had no disclosures related to his talk.
LAS VEGAS – Although circulating tumor cells are prognostic in breast cancer, they aren’t likely to become a part of routine practice until they’ve been shown to improve outcomes, and that hasn’t happened yet, according to Anthony Lucci, MD, professor of breast surgical oncology at MD Anderson Cancer Center, Houston.
MD Anderson and other institutions have established that in breast cancer, from baseline through treatment follow-up, the presence of circulating tumor cells (CTCs) in the blood predicts worse outcomes in both metastatic and local disease, even among women who have a pathologic complete response to treatment.
That knowledge has not yet translated into better outcomes. In a pivotal trial, survival was no better in metastatic breast cancer when women were switched to an alternative chemotherapy regimen after their CTC levels did not fall in response to first-line treatment, compared with women who remained on their initial agent despite persistently high CTCs (J Clin Oncol. 2014 Nov 1;32[31]:3483-9).
“When we tried to switch chemotherapy” based on CTCs, “it really didn’t make a difference, so no one is really quite sure yet what to do with this information. We can’t tell a patient that they are likely to have a much worse outcome, but there’s nothing we can do about it,” and “I don’t think payers will pay” for CTC testing in breast cancer until “we establish a predictive benefit, and show what agents will reduce CTCs and improve outcomes,” Dr. Lucci said at the American Society of Breast Surgeons annual meeting.
Even so, the promise of CTCs as a clinical tool is too great to abandon research, and work continues at MD Anderson and elsewhere. It’s thought that tumor cells in the blood aren’t simply a marker of disease, but rather microscopic disease in themselves that contributes to recurrence and progression. It’s possible that cells shed by tumors lie dormant in the bone marrow, then reactivate and reseed the original tumor site or give rise to distant metastases.
CTCs are similar to tumor cells that have been found in the bone marrow of women with apparently quiescent breast cancer, but finding them in the blood means “you don’t have to poke a needle in someone’s bone. You can just take a sample of their blood, and it tells you the same information,” Dr. Lucci said.
CTCs have been shown in breast cancer to rise and fall depending on tumor response. “In the future, I do think we will [use them] as a serial monitoring tool and a guide to therapy.” There might even be a role for breast cancer screening, he said.
Analyzing the blood for evidence of solid tumors – popularly called “liquid biopsy” – has shown benefits in a variety of cancers, particularly for identifying disease, and in some cases mutations, sooner than with conventional methods. Science is catching up to the old-school notion that cancer spreads through the blood.
Another approach is to look for circulating tumor DNA, which has been shown to be useful for early detection in gynecologic cancers. The idea is that a few tumor cells shatter and spill their genetic material into the blood early on. “In the majority of breast cancer patients,” however, “you don’t find actionable mutations” with circulating tumor DNA, especially in earlier-stage, nonmetastatic disease. “There’s not enough DNA released into the blood,” Dr. Lucci said.
But “we need to be monitoring the blood on a routine basis” for breast cancer clues. “That, I think, is the wave of the future. Just looking at x-rays and waiting for something to happen is too late,” he said.
Dr. Lucci had no disclosures related to his talk.
LAS VEGAS – Although circulating tumor cells are prognostic in breast cancer, they aren’t likely to become a part of routine practice until they’ve been shown to improve outcomes, and that hasn’t happened yet, according to Anthony Lucci, MD, professor of breast surgical oncology at MD Anderson Cancer Center, Houston.
MD Anderson and other institutions have established that in breast cancer, from baseline through treatment follow-up, the presence of circulating tumor cells (CTCs) in the blood predicts worse outcomes in both metastatic and local disease, even among women who have a pathologic complete response to treatment.
That knowledge has not yet translated into better outcomes. In a pivotal trial, survival was no better in metastatic breast cancer when women were switched to an alternative chemotherapy regimen after their CTC levels did not fall in response to first-line treatment, compared with women who remained on their initial agent despite persistently high CTCs (J Clin Oncol. 2014 Nov 1;32[31]:3483-9).
“When we tried to switch chemotherapy” based on CTCs, “it really didn’t make a difference, so no one is really quite sure yet what to do with this information. We can’t tell a patient that they are likely to have a much worse outcome, but there’s nothing we can do about it,” and “I don’t think payers will pay” for CTC testing in breast cancer until “we establish a predictive benefit, and show what agents will reduce CTCs and improve outcomes,” Dr. Lucci said at the American Society of Breast Surgeons annual meeting.
Even so, the promise of CTCs as a clinical tool is too great to abandon research, and work continues at MD Anderson and elsewhere. It’s thought that tumor cells in the blood aren’t simply a marker of disease, but rather microscopic disease in themselves that contributes to recurrence and progression. It’s possible that cells shed by tumors lie dormant in the bone marrow, then reactivate and reseed the original tumor site or give rise to distant metastases.
CTCs are similar to tumor cells that have been found in the bone marrow of women with apparently quiescent breast cancer, but finding them in the blood means “you don’t have to poke a needle in someone’s bone. You can just take a sample of their blood, and it tells you the same information,” Dr. Lucci said.
CTCs have been shown in breast cancer to rise and fall depending on tumor response. “In the future, I do think we will [use them] as a serial monitoring tool and a guide to therapy.” There might even be a role for breast cancer screening, he said.
Analyzing the blood for evidence of solid tumors – popularly called “liquid biopsy” – has shown benefits in a variety of cancers, particularly for identifying disease, and in some cases mutations, sooner than with conventional methods. Science is catching up to the old-school notion that cancer spreads through the blood.
Another approach is to look for circulating tumor DNA, which has been shown to be useful for early detection in gynecologic cancers. The idea is that a few tumor cells shatter and spill their genetic material into the blood early on. “In the majority of breast cancer patients,” however, “you don’t find actionable mutations” with circulating tumor DNA, especially in earlier-stage, nonmetastatic disease. “There’s not enough DNA released into the blood,” Dr. Lucci said.
But “we need to be monitoring the blood on a routine basis” for breast cancer clues. “That, I think, is the wave of the future. Just looking at x-rays and waiting for something to happen is too late,” he said.
Dr. Lucci had no disclosures related to his talk.
AT ASBS 2017
Five year survival doubles for younger women with de novo MBC
Nearly 155,000 women in the United States are living with metastatic breast cancer (MBC), three-fourths of whom were initially diagnosed with lower-stage disease that progressed to stage IV, based on estimated prevalence data.
The estimates, derived from national breast cancer mortality and survival data, also show positive trends in breast cancer care, especially a doubling of 5-year survival rates among younger women diagnosed with de novo metastatic disease from the 1990s to the 2000s, reported Angela B. Mariotto, PhD, of the National Cancer Institute and her colleagues.
“Despite the progressive and incurable nature of almost all MBC, median survival after diagnosis with metastatic disease has been increasing, resulting in a growing number of women living with MBC in the United States. The increased survival is especially noted for women diagnosed at younger ages,” they wrote in Cancer Epidemiology, Biomarkers, & Prevention (2017 May 18. doi: 10.1158/1055-9965.epi-16-088).
Patients with advanced breast cancer require extensive care and intensive use of medical and other resources, but, until this study, there were no reliable estimates of the number of women actually living with metastatic disease in the United States, the authors said.
To get a clearer picture of the prevalence of advanced breast cancer in the United States, they worked backward from Surveillance, Epidemiology, and End Results data on breast cancer deaths and survival, working on the assumption that each observed breast cancer death is the result of metastatic disease, either in women whose initial diagnosis was stage IV disease (de novo metastatic disease) or disease recurrence with metastases.
They estimated that, in 2013, the most recent year for which there were observed data, the prevalence of metastatic breast cancer was 138,622, and that 38,897 (28%) of survivors were diagnosed with metastatic disease. The remaining 99,725 survivors (72%) were women who were initially diagnosed with stage I-III disease that either recurred or metastasized.
The authors calculated that 50,344 women were diagnosed with de novo metastatic disease in 2013, 12,966 of whom (26%) had de novo metastatic breast cancer and 37,378 of whom had recurrent disease. They projected that, as of Jan. 1, 2017, there are 154,794 women living with metastatic breast cancer in the United States.
They also estimated changes over time in survival and found that, for women diagnosed from the ages of 15 to 49 during the 1992-1994 surveillance period, median survival time was 22.3 months, which improved to 38.7 months during the 2005-2012 surveillance period. The respective survival times for women 50-64 years were 19.1 months and 29.7 months.
For women 15-49 years who were diagnosed with de novo metastatic breast cancer, the 5-year relative survival rates doubled from 18% during 1992-1994 to 36% during 2005-2012.
“Despite a poor prognosis, there is a small but meaningful percentage of these cases who survive 10 years or more. More than 11% of women diagnosed between 2000-2004 under the age of 64 years survived 10 years or more. Younger women diagnosed with de novo MBC have higher survival than women diagnosed at older ages,” Dr. Mariotto and her colleagues wrote.
The investigators pointed to the population size, population-based data, long follow-up, and use of consistent staging definitions over time as study strengths but acknowledged that the study was limited by the absence of population-based estimates of survival following recurrence of metastatic breast cancer.
“To our knowledge, this is the first time that the number of women living with MBC in the United States has been estimated. These estimates provide a new perspective on the population burden of breast cancer and have great potential significance to the research and advocacy community working on behalf of patients with MBC and their families,” the authors wrote.
The study was supported by the National Cancer Institute. The authors reported no relevant financial disclosures.
This article was updated June 5, 2017.
Nearly 155,000 women in the United States are living with metastatic breast cancer (MBC), three-fourths of whom were initially diagnosed with lower-stage disease that progressed to stage IV, based on estimated prevalence data.
The estimates, derived from national breast cancer mortality and survival data, also show positive trends in breast cancer care, especially a doubling of 5-year survival rates among younger women diagnosed with de novo metastatic disease from the 1990s to the 2000s, reported Angela B. Mariotto, PhD, of the National Cancer Institute and her colleagues.
“Despite the progressive and incurable nature of almost all MBC, median survival after diagnosis with metastatic disease has been increasing, resulting in a growing number of women living with MBC in the United States. The increased survival is especially noted for women diagnosed at younger ages,” they wrote in Cancer Epidemiology, Biomarkers, & Prevention (2017 May 18. doi: 10.1158/1055-9965.epi-16-088).
Patients with advanced breast cancer require extensive care and intensive use of medical and other resources, but, until this study, there were no reliable estimates of the number of women actually living with metastatic disease in the United States, the authors said.
To get a clearer picture of the prevalence of advanced breast cancer in the United States, they worked backward from Surveillance, Epidemiology, and End Results data on breast cancer deaths and survival, working on the assumption that each observed breast cancer death is the result of metastatic disease, either in women whose initial diagnosis was stage IV disease (de novo metastatic disease) or disease recurrence with metastases.
They estimated that, in 2013, the most recent year for which there were observed data, the prevalence of metastatic breast cancer was 138,622, and that 38,897 (28%) of survivors were diagnosed with metastatic disease. The remaining 99,725 survivors (72%) were women who were initially diagnosed with stage I-III disease that either recurred or metastasized.
The authors calculated that 50,344 women were diagnosed with de novo metastatic disease in 2013, 12,966 of whom (26%) had de novo metastatic breast cancer and 37,378 of whom had recurrent disease. They projected that, as of Jan. 1, 2017, there are 154,794 women living with metastatic breast cancer in the United States.
They also estimated changes over time in survival and found that, for women diagnosed from the ages of 15 to 49 during the 1992-1994 surveillance period, median survival time was 22.3 months, which improved to 38.7 months during the 2005-2012 surveillance period. The respective survival times for women 50-64 years were 19.1 months and 29.7 months.
For women 15-49 years who were diagnosed with de novo metastatic breast cancer, the 5-year relative survival rates doubled from 18% during 1992-1994 to 36% during 2005-2012.
“Despite a poor prognosis, there is a small but meaningful percentage of these cases who survive 10 years or more. More than 11% of women diagnosed between 2000-2004 under the age of 64 years survived 10 years or more. Younger women diagnosed with de novo MBC have higher survival than women diagnosed at older ages,” Dr. Mariotto and her colleagues wrote.
The investigators pointed to the population size, population-based data, long follow-up, and use of consistent staging definitions over time as study strengths but acknowledged that the study was limited by the absence of population-based estimates of survival following recurrence of metastatic breast cancer.
“To our knowledge, this is the first time that the number of women living with MBC in the United States has been estimated. These estimates provide a new perspective on the population burden of breast cancer and have great potential significance to the research and advocacy community working on behalf of patients with MBC and their families,” the authors wrote.
The study was supported by the National Cancer Institute. The authors reported no relevant financial disclosures.
This article was updated June 5, 2017.
Nearly 155,000 women in the United States are living with metastatic breast cancer (MBC), three-fourths of whom were initially diagnosed with lower-stage disease that progressed to stage IV, based on estimated prevalence data.
The estimates, derived from national breast cancer mortality and survival data, also show positive trends in breast cancer care, especially a doubling of 5-year survival rates among younger women diagnosed with de novo metastatic disease from the 1990s to the 2000s, reported Angela B. Mariotto, PhD, of the National Cancer Institute and her colleagues.
“Despite the progressive and incurable nature of almost all MBC, median survival after diagnosis with metastatic disease has been increasing, resulting in a growing number of women living with MBC in the United States. The increased survival is especially noted for women diagnosed at younger ages,” they wrote in Cancer Epidemiology, Biomarkers, & Prevention (2017 May 18. doi: 10.1158/1055-9965.epi-16-088).
Patients with advanced breast cancer require extensive care and intensive use of medical and other resources, but, until this study, there were no reliable estimates of the number of women actually living with metastatic disease in the United States, the authors said.
To get a clearer picture of the prevalence of advanced breast cancer in the United States, they worked backward from Surveillance, Epidemiology, and End Results data on breast cancer deaths and survival, working on the assumption that each observed breast cancer death is the result of metastatic disease, either in women whose initial diagnosis was stage IV disease (de novo metastatic disease) or disease recurrence with metastases.
They estimated that, in 2013, the most recent year for which there were observed data, the prevalence of metastatic breast cancer was 138,622, and that 38,897 (28%) of survivors were diagnosed with metastatic disease. The remaining 99,725 survivors (72%) were women who were initially diagnosed with stage I-III disease that either recurred or metastasized.
The authors calculated that 50,344 women were diagnosed with de novo metastatic disease in 2013, 12,966 of whom (26%) had de novo metastatic breast cancer and 37,378 of whom had recurrent disease. They projected that, as of Jan. 1, 2017, there are 154,794 women living with metastatic breast cancer in the United States.
They also estimated changes over time in survival and found that, for women diagnosed from the ages of 15 to 49 during the 1992-1994 surveillance period, median survival time was 22.3 months, which improved to 38.7 months during the 2005-2012 surveillance period. The respective survival times for women 50-64 years were 19.1 months and 29.7 months.
For women 15-49 years who were diagnosed with de novo metastatic breast cancer, the 5-year relative survival rates doubled from 18% during 1992-1994 to 36% during 2005-2012.
“Despite a poor prognosis, there is a small but meaningful percentage of these cases who survive 10 years or more. More than 11% of women diagnosed between 2000-2004 under the age of 64 years survived 10 years or more. Younger women diagnosed with de novo MBC have higher survival than women diagnosed at older ages,” Dr. Mariotto and her colleagues wrote.
The investigators pointed to the population size, population-based data, long follow-up, and use of consistent staging definitions over time as study strengths but acknowledged that the study was limited by the absence of population-based estimates of survival following recurrence of metastatic breast cancer.
“To our knowledge, this is the first time that the number of women living with MBC in the United States has been estimated. These estimates provide a new perspective on the population burden of breast cancer and have great potential significance to the research and advocacy community working on behalf of patients with MBC and their families,” the authors wrote.
The study was supported by the National Cancer Institute. The authors reported no relevant financial disclosures.
This article was updated June 5, 2017.
FROM CANCER EPIDEMIOLOGY, BIOMARKERS & PREVENTION
Key clinical point: An estimated 155,000 women are living with metastatic breast cancer in the United States.
Major finding: Among women diagnosed from ages 15 to 49 with de novo metastatic breast cancer, the 5-year relative survival doubled from 18% during 1992-1994 to 36% during 2005-2012.
Data source: An epidemiologic estimate of metastatic breast cancer prevalence in the United States using SEER data.
Disclosures: The study was supported by the National Cancer Institute. The authors reported no relevant financial disclosures.
Continuing tamoxifen costs less, performs better in ER+ breast cancer
AT ACOG 2017
SAN DIEGO – Continuation of tamoxifen for an additional 5 years is a cost-effective strategy that does not increase all-cause mortality for premenopausal women with estrogen receptor–positive breast cancer, based on an analysis using sophisticated computational modeling techniques.
“For premenopausal women with an early estrogen receptor–positive breast cancer who have completed 5 years of tamoxifen as initial treatment, another 5 years of tamoxifen is preferable to ovarian ablation with an aromatase inhibitor as extended endocrine treatment,” Janice Kwon, MD, said at the annual meeting of the American College of Obstetricians and Gynecologists.
The researchers sought to answer a key clinical question: “What is the optimal endocrine strategy for premenopausal women who have completed 5 years of tamoxifen? Another 5 years of tamoxifen? An aromatase inhibitor preceded by ovarian ablation? Or no further treatment?”
Dr. Kwon and her coinvestigators used a Markov Monte Carlo simulation to project adverse events that would occur with each of the three treatments in a hypothetical cohort of 18,000 premenopausal women with estrogen receptor–positive breast cancer. They also conducted sensitivity analyses to ascertain the point at which a given treatment would become cost effective. The investigators used a time horizon of 40 years in the Monte Carlo simulation, which uses repeated random sampling of a large data set to model the probability of a variety of outcomes. The primary outcome measure used to compare the three treatment strategies was the incremental cost-effectiveness ratio (ICER).
For the no further treatment strategy, the average costs were $1,074, for an average life expectancy gain of 16.69 years. Compared with this strategy, 5 more years of tamoxifen would cost $3,550 for an average life expectancy gain of 17.31 years, yielding an ICER of $4,042. The strategy of performing a bilateral salpingo-oophorectomy (BSO), followed by 5 years of aromatase inhibitor therapy, was more costly at $14,312 and yielded a shorter life expectancy gain at an average of 17.06 years, eliminating it as a feasible strategy in the ICER analysis.
Using the Monte Carlo simulation to assess treatment-related mortality, Dr. Kwon and her colleagues found that no further treatment would result in the most deaths from breast cancer, at 7,358. For this, and each of the other two strategies, the investigators also modeled deaths from other causes and from early BSO, using the Nurses’ Health Study hazard ratios. No further treatment would result in 5,878 deaths from other causes and none from early BSO, for a total of 13,236.
Another 5 years of tamoxifen, the model showed, would result in 6,227 deaths from breast cancer, 6,330 from other causes, and none from BSO, for a total of 12,557.
The BSO–aromatase inhibitor strategy was modeled to have the fewest deaths from breast cancer (5,504) and from other causes (5,834) but would result in an additional 1,897 deaths from the early BSO. The BSO–aromatase inhibitor strategy thus resulted in a virtually identical number of deaths over a 40-year period as no treatment at all, at 13,235.
An aromatase inhibitor is frequently considered as a treatment strategy for women with estrogen receptor–positive breast cancer. However, using an aromatase inhibitor is predicated on the patient being menopausal, so ovarian ablation is recommended for patients who have, or who may have, intact ovarian function.
Nearly 3 decades’ worth of data from the Nurses’ Health Study showed an overall hazard ratio of 1.41 for premenopausal oophorectomy without hormone therapy, said Dr. Kwon of the gynecologic oncology division at the University of British Columbia, Vancouver. Increased rates of osteoporosis, stroke, and coronary heart disease contributed to the increased risk, with 80% of the excess deaths occurring within 15 years of oophorectomy. The analysis yielded a number needed to harm for the procedure of eight.
The study’s results have also been substantiated by a recent meta-analysis, said Dr. Kwon, that also saw “fewer disease-free events but more deaths with aromatase inhibitor versus tamoxifen” (Breast Cancer Res Treat. 2017;161:185-90). However, she said, the long-term outcomes of breast cancer over many decades are unknown, and the analysis did not include costs for treatment of recurrent breast cancer.
No external funding sources were reported, and Dr. Kwon reported having no relevant financial disclosures.
[email protected]
On Twitter @karioakes
AT ACOG 2017
SAN DIEGO – Continuation of tamoxifen for an additional 5 years is a cost-effective strategy that does not increase all-cause mortality for premenopausal women with estrogen receptor–positive breast cancer, based on an analysis using sophisticated computational modeling techniques.
“For premenopausal women with an early estrogen receptor–positive breast cancer who have completed 5 years of tamoxifen as initial treatment, another 5 years of tamoxifen is preferable to ovarian ablation with an aromatase inhibitor as extended endocrine treatment,” Janice Kwon, MD, said at the annual meeting of the American College of Obstetricians and Gynecologists.
The researchers sought to answer a key clinical question: “What is the optimal endocrine strategy for premenopausal women who have completed 5 years of tamoxifen? Another 5 years of tamoxifen? An aromatase inhibitor preceded by ovarian ablation? Or no further treatment?”
Dr. Kwon and her coinvestigators used a Markov Monte Carlo simulation to project adverse events that would occur with each of the three treatments in a hypothetical cohort of 18,000 premenopausal women with estrogen receptor–positive breast cancer. They also conducted sensitivity analyses to ascertain the point at which a given treatment would become cost effective. The investigators used a time horizon of 40 years in the Monte Carlo simulation, which uses repeated random sampling of a large data set to model the probability of a variety of outcomes. The primary outcome measure used to compare the three treatment strategies was the incremental cost-effectiveness ratio (ICER).
For the no further treatment strategy, the average costs were $1,074, for an average life expectancy gain of 16.69 years. Compared with this strategy, 5 more years of tamoxifen would cost $3,550 for an average life expectancy gain of 17.31 years, yielding an ICER of $4,042. The strategy of performing a bilateral salpingo-oophorectomy (BSO), followed by 5 years of aromatase inhibitor therapy, was more costly at $14,312 and yielded a shorter life expectancy gain at an average of 17.06 years, eliminating it as a feasible strategy in the ICER analysis.
Using the Monte Carlo simulation to assess treatment-related mortality, Dr. Kwon and her colleagues found that no further treatment would result in the most deaths from breast cancer, at 7,358. For this, and each of the other two strategies, the investigators also modeled deaths from other causes and from early BSO, using the Nurses’ Health Study hazard ratios. No further treatment would result in 5,878 deaths from other causes and none from early BSO, for a total of 13,236.
Another 5 years of tamoxifen, the model showed, would result in 6,227 deaths from breast cancer, 6,330 from other causes, and none from BSO, for a total of 12,557.
The BSO–aromatase inhibitor strategy was modeled to have the fewest deaths from breast cancer (5,504) and from other causes (5,834) but would result in an additional 1,897 deaths from the early BSO. The BSO–aromatase inhibitor strategy thus resulted in a virtually identical number of deaths over a 40-year period as no treatment at all, at 13,235.
An aromatase inhibitor is frequently considered as a treatment strategy for women with estrogen receptor–positive breast cancer. However, using an aromatase inhibitor is predicated on the patient being menopausal, so ovarian ablation is recommended for patients who have, or who may have, intact ovarian function.
Nearly 3 decades’ worth of data from the Nurses’ Health Study showed an overall hazard ratio of 1.41 for premenopausal oophorectomy without hormone therapy, said Dr. Kwon of the gynecologic oncology division at the University of British Columbia, Vancouver. Increased rates of osteoporosis, stroke, and coronary heart disease contributed to the increased risk, with 80% of the excess deaths occurring within 15 years of oophorectomy. The analysis yielded a number needed to harm for the procedure of eight.
The study’s results have also been substantiated by a recent meta-analysis, said Dr. Kwon, that also saw “fewer disease-free events but more deaths with aromatase inhibitor versus tamoxifen” (Breast Cancer Res Treat. 2017;161:185-90). However, she said, the long-term outcomes of breast cancer over many decades are unknown, and the analysis did not include costs for treatment of recurrent breast cancer.
No external funding sources were reported, and Dr. Kwon reported having no relevant financial disclosures.
[email protected]
On Twitter @karioakes
AT ACOG 2017
SAN DIEGO – Continuation of tamoxifen for an additional 5 years is a cost-effective strategy that does not increase all-cause mortality for premenopausal women with estrogen receptor–positive breast cancer, based on an analysis using sophisticated computational modeling techniques.
“For premenopausal women with an early estrogen receptor–positive breast cancer who have completed 5 years of tamoxifen as initial treatment, another 5 years of tamoxifen is preferable to ovarian ablation with an aromatase inhibitor as extended endocrine treatment,” Janice Kwon, MD, said at the annual meeting of the American College of Obstetricians and Gynecologists.
The researchers sought to answer a key clinical question: “What is the optimal endocrine strategy for premenopausal women who have completed 5 years of tamoxifen? Another 5 years of tamoxifen? An aromatase inhibitor preceded by ovarian ablation? Or no further treatment?”
Dr. Kwon and her coinvestigators used a Markov Monte Carlo simulation to project adverse events that would occur with each of the three treatments in a hypothetical cohort of 18,000 premenopausal women with estrogen receptor–positive breast cancer. They also conducted sensitivity analyses to ascertain the point at which a given treatment would become cost effective. The investigators used a time horizon of 40 years in the Monte Carlo simulation, which uses repeated random sampling of a large data set to model the probability of a variety of outcomes. The primary outcome measure used to compare the three treatment strategies was the incremental cost-effectiveness ratio (ICER).
For the no further treatment strategy, the average costs were $1,074, for an average life expectancy gain of 16.69 years. Compared with this strategy, 5 more years of tamoxifen would cost $3,550 for an average life expectancy gain of 17.31 years, yielding an ICER of $4,042. The strategy of performing a bilateral salpingo-oophorectomy (BSO), followed by 5 years of aromatase inhibitor therapy, was more costly at $14,312 and yielded a shorter life expectancy gain at an average of 17.06 years, eliminating it as a feasible strategy in the ICER analysis.
Using the Monte Carlo simulation to assess treatment-related mortality, Dr. Kwon and her colleagues found that no further treatment would result in the most deaths from breast cancer, at 7,358. For this, and each of the other two strategies, the investigators also modeled deaths from other causes and from early BSO, using the Nurses’ Health Study hazard ratios. No further treatment would result in 5,878 deaths from other causes and none from early BSO, for a total of 13,236.
Another 5 years of tamoxifen, the model showed, would result in 6,227 deaths from breast cancer, 6,330 from other causes, and none from BSO, for a total of 12,557.
The BSO–aromatase inhibitor strategy was modeled to have the fewest deaths from breast cancer (5,504) and from other causes (5,834) but would result in an additional 1,897 deaths from the early BSO. The BSO–aromatase inhibitor strategy thus resulted in a virtually identical number of deaths over a 40-year period as no treatment at all, at 13,235.
An aromatase inhibitor is frequently considered as a treatment strategy for women with estrogen receptor–positive breast cancer. However, using an aromatase inhibitor is predicated on the patient being menopausal, so ovarian ablation is recommended for patients who have, or who may have, intact ovarian function.
Nearly 3 decades’ worth of data from the Nurses’ Health Study showed an overall hazard ratio of 1.41 for premenopausal oophorectomy without hormone therapy, said Dr. Kwon of the gynecologic oncology division at the University of British Columbia, Vancouver. Increased rates of osteoporosis, stroke, and coronary heart disease contributed to the increased risk, with 80% of the excess deaths occurring within 15 years of oophorectomy. The analysis yielded a number needed to harm for the procedure of eight.
The study’s results have also been substantiated by a recent meta-analysis, said Dr. Kwon, that also saw “fewer disease-free events but more deaths with aromatase inhibitor versus tamoxifen” (Breast Cancer Res Treat. 2017;161:185-90). However, she said, the long-term outcomes of breast cancer over many decades are unknown, and the analysis did not include costs for treatment of recurrent breast cancer.
No external funding sources were reported, and Dr. Kwon reported having no relevant financial disclosures.
[email protected]
On Twitter @karioakes
Key clinical point:
Major finding: Continuation of tamoxifen for 5 more years resulted in 678 fewer deaths than did receipt of an aromatase inhibitor and oophorectomy in a hypothetical cohort of 18,000 women.
Data source: Monte Carlo simulation and sensitivity analysis of a hypothetical cohort of 18,000 premenopausal women with estrogen receptor–positive breast cancer.
Disclosures: No external funding sources were reported, and the researchers reported having no relevant financial disclosures.
Intraoperative radiation looks good for DCIS
LAS VEGAS – Intraoperative radiation therapy (IORT) is effective in patients with ductal carcinoma in situ (DCIS), and bilateral digital mammography and breast MRI effectively predicted which patients would be most suited for the procedure, according to a nonrandomized study.
The TARGIT-A trial showed that IORT was noninferior to external beam radiation therapy in women with early-stage breast cancer (Lancet. 2014 Feb 15;383:603-13), but the technique hasn’t been tested in DCIS patients.
The researchers conducted a prospective, nonrandomized study of DCIS in women who underwent core biopsy between February 2012 and July 2016 at Virginia Mason Medical Center. Those who elected breast conserving therapy were assessed for IORT using bilateral digital mammography and contrast enhanced MRI.
For criteria, the researchers selected patients over age 44 years with unifocal DCIS and a lesion size of up to 3.0 cm. Physicians recommended additional therapy when the pathology report revealed DCIS larger than 3 cm and/or margins of up to 2 mm.
Of the 57 patients initially enrolled, 7 were found to have invasive disease and were excluded. Another eight patients were excluded because of margins, tumor size, or multifocal disease, and were recommended for additional treatment.
The remaining 42 patients with DCIS were treated with IORT. At a mean follow-up time of 32 months, the researchers observed no local recurrences, and no Radiation Therapy Oncology Group grade 3 or 4 complications were reported.
Hyperpigmentation occurred more often in the IORT group, at 40% (17 of 42 patients), than in the additional treatment group, at 13% (1 of 8), a nonsignificant difference. The hyperpigmentation tended to be minimal and focused on the surgical scar. There were no differences between the groups with respect to superficial wound separation, infection, seroma, fat necrosis, transient radiation dermatitis, or rib fracture.
“Our conclusions are that are selection criteria with mammography and MRI are effective in identifying patients who are appropriate for IORT, and importantly, at 32 months follow-up, no patients had recurrences, so we’re not negatively impacting oncological outcome,” said Dr. Carlson.
The fact that eight patients were recommended for additional treatment based on margins, a disease span greater than 3 cm, or multifocal disease “is actually quite heartening because it implies that the mammogram and the MRI are quite effective at identifying patients that met our criteria,” said Dr. Carlson.
The study is small and had no control group, but Dr. Carlson is confident of the results. “We didn’t do a randomized trial because we believed strongly that IORT will be effective in these patients with good cosmesis. When you compare it to local recurrence rates in the TARGIT-A trial, we’re still doing quite well, so to some extent that can be used as a baseline benchmark,” she said.
LAS VEGAS – Intraoperative radiation therapy (IORT) is effective in patients with ductal carcinoma in situ (DCIS), and bilateral digital mammography and breast MRI effectively predicted which patients would be most suited for the procedure, according to a nonrandomized study.
The TARGIT-A trial showed that IORT was noninferior to external beam radiation therapy in women with early-stage breast cancer (Lancet. 2014 Feb 15;383:603-13), but the technique hasn’t been tested in DCIS patients.
The researchers conducted a prospective, nonrandomized study of DCIS in women who underwent core biopsy between February 2012 and July 2016 at Virginia Mason Medical Center. Those who elected breast conserving therapy were assessed for IORT using bilateral digital mammography and contrast enhanced MRI.
For criteria, the researchers selected patients over age 44 years with unifocal DCIS and a lesion size of up to 3.0 cm. Physicians recommended additional therapy when the pathology report revealed DCIS larger than 3 cm and/or margins of up to 2 mm.
Of the 57 patients initially enrolled, 7 were found to have invasive disease and were excluded. Another eight patients were excluded because of margins, tumor size, or multifocal disease, and were recommended for additional treatment.
The remaining 42 patients with DCIS were treated with IORT. At a mean follow-up time of 32 months, the researchers observed no local recurrences, and no Radiation Therapy Oncology Group grade 3 or 4 complications were reported.
Hyperpigmentation occurred more often in the IORT group, at 40% (17 of 42 patients), than in the additional treatment group, at 13% (1 of 8), a nonsignificant difference. The hyperpigmentation tended to be minimal and focused on the surgical scar. There were no differences between the groups with respect to superficial wound separation, infection, seroma, fat necrosis, transient radiation dermatitis, or rib fracture.
“Our conclusions are that are selection criteria with mammography and MRI are effective in identifying patients who are appropriate for IORT, and importantly, at 32 months follow-up, no patients had recurrences, so we’re not negatively impacting oncological outcome,” said Dr. Carlson.
The fact that eight patients were recommended for additional treatment based on margins, a disease span greater than 3 cm, or multifocal disease “is actually quite heartening because it implies that the mammogram and the MRI are quite effective at identifying patients that met our criteria,” said Dr. Carlson.
The study is small and had no control group, but Dr. Carlson is confident of the results. “We didn’t do a randomized trial because we believed strongly that IORT will be effective in these patients with good cosmesis. When you compare it to local recurrence rates in the TARGIT-A trial, we’re still doing quite well, so to some extent that can be used as a baseline benchmark,” she said.
LAS VEGAS – Intraoperative radiation therapy (IORT) is effective in patients with ductal carcinoma in situ (DCIS), and bilateral digital mammography and breast MRI effectively predicted which patients would be most suited for the procedure, according to a nonrandomized study.
The TARGIT-A trial showed that IORT was noninferior to external beam radiation therapy in women with early-stage breast cancer (Lancet. 2014 Feb 15;383:603-13), but the technique hasn’t been tested in DCIS patients.
The researchers conducted a prospective, nonrandomized study of DCIS in women who underwent core biopsy between February 2012 and July 2016 at Virginia Mason Medical Center. Those who elected breast conserving therapy were assessed for IORT using bilateral digital mammography and contrast enhanced MRI.
For criteria, the researchers selected patients over age 44 years with unifocal DCIS and a lesion size of up to 3.0 cm. Physicians recommended additional therapy when the pathology report revealed DCIS larger than 3 cm and/or margins of up to 2 mm.
Of the 57 patients initially enrolled, 7 were found to have invasive disease and were excluded. Another eight patients were excluded because of margins, tumor size, or multifocal disease, and were recommended for additional treatment.
The remaining 42 patients with DCIS were treated with IORT. At a mean follow-up time of 32 months, the researchers observed no local recurrences, and no Radiation Therapy Oncology Group grade 3 or 4 complications were reported.
Hyperpigmentation occurred more often in the IORT group, at 40% (17 of 42 patients), than in the additional treatment group, at 13% (1 of 8), a nonsignificant difference. The hyperpigmentation tended to be minimal and focused on the surgical scar. There were no differences between the groups with respect to superficial wound separation, infection, seroma, fat necrosis, transient radiation dermatitis, or rib fracture.
“Our conclusions are that are selection criteria with mammography and MRI are effective in identifying patients who are appropriate for IORT, and importantly, at 32 months follow-up, no patients had recurrences, so we’re not negatively impacting oncological outcome,” said Dr. Carlson.
The fact that eight patients were recommended for additional treatment based on margins, a disease span greater than 3 cm, or multifocal disease “is actually quite heartening because it implies that the mammogram and the MRI are quite effective at identifying patients that met our criteria,” said Dr. Carlson.
The study is small and had no control group, but Dr. Carlson is confident of the results. “We didn’t do a randomized trial because we believed strongly that IORT will be effective in these patients with good cosmesis. When you compare it to local recurrence rates in the TARGIT-A trial, we’re still doing quite well, so to some extent that can be used as a baseline benchmark,” she said.
AT ASBS 2017
Key clinical point: Intraoperative radiation appears safe and effective, and is more convenient than postoperative radiation.
Major finding: There were no ductal carcinoma in situ recurrences at a median 32 months’ follow-up.
Data source: Uncontrolled, prospective study of 42 patients.
Disclosures: The study was funded by the National Institutes of Health. Dr. Carlson reported having no financial disclosures.
Positive node risk defined for elderly breast cancer patients
LAS VEGAS – In women aged 70 years or older with hormone receptor–positive invasive breast cancer, their tumor size, grade, and histology – but not human epidermal growth factor receptor–2 status – predicted nodal positivity, according to a retrospective analysis.
Investigators at the Mayo Clinic, Rochester, Minn., reviewed 52,532 women in the National Cancer Database from 2010 to 2013 who were at least 70 years old with hormone receptor–positive invasive breast cancer and clinically node negative disease, who had axillary surgery performed. Two-thirds of the cohort was used to identify risk factors, and the remaining third to validate them. About 16% in both groups had cancer in their axillary lymph nodes.
On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes. Although significant on univariate analysis, age (P = .57) and HER2 status (P = .32) fell out on multivariate analysis.
Nodal positivity was more than five times as likely with clinical T2 tumors, compared with T1a tumors, and far less likely for patients with invasive mucinous carcinoma than for those with invasive ductal carcinoma.
The team expects to release a nomogram for general use in clinical practice to predict the risk of positive nodes for various combinations of tumor size, grade, and histology in older women. When the model predicted a less than 10% chance of node positive disease, the actual rate in the validation set was around 5.5%. When it predicted a 30%-39% chance, the actual rate was 32.6%. The area under the receiver operating characteristic curve was 0.7 in both the development and validation sets, indicating good discrimination.
The work grew out of an effort to implement the Society of Surgical Oncologists’ recommendation not to do routine sentinel node biopsies in clinically node negative, hormone receptor–positive invasive breast cancer in women over the age of 70 years, a recommendation the group made as part of its contribution to the Choosing Wisely campaign.
“After the guideline was released, we were sitting in the clinic thinking how to apply it to our patients,” lead investigator Jessemae Welsh, MD, a surgeon at the Mayo Clinic, said at the American Society of Breast Surgeons annual meeting.
The problem is that nodal positivity is important to know for other aspects of care, including regional nodal irradiation and duration of systemic hormone therapy, and axillary lymph node staging might still be indicated if older women are truly at high risk. “We [wanted] to develop a multivariate model that gives a precise estimate of nodal risk,” to help “patients and surgeons to decide together based on an individual risk” how best to proceed. Also, a prediction of low risk “can help reassure patients that they will do well without axillary surgery,” she said.
Mayo’s nomogram is unique in that it focuses specifically on women 70 years and older. Development of previous nomograms incorporated older women, but did not focus on them specifically, Dr. Welsh said.
Dr. Welsh said she had no relevant disclosures.
[email protected]
LAS VEGAS – In women aged 70 years or older with hormone receptor–positive invasive breast cancer, their tumor size, grade, and histology – but not human epidermal growth factor receptor–2 status – predicted nodal positivity, according to a retrospective analysis.
Investigators at the Mayo Clinic, Rochester, Minn., reviewed 52,532 women in the National Cancer Database from 2010 to 2013 who were at least 70 years old with hormone receptor–positive invasive breast cancer and clinically node negative disease, who had axillary surgery performed. Two-thirds of the cohort was used to identify risk factors, and the remaining third to validate them. About 16% in both groups had cancer in their axillary lymph nodes.
On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes. Although significant on univariate analysis, age (P = .57) and HER2 status (P = .32) fell out on multivariate analysis.
Nodal positivity was more than five times as likely with clinical T2 tumors, compared with T1a tumors, and far less likely for patients with invasive mucinous carcinoma than for those with invasive ductal carcinoma.
The team expects to release a nomogram for general use in clinical practice to predict the risk of positive nodes for various combinations of tumor size, grade, and histology in older women. When the model predicted a less than 10% chance of node positive disease, the actual rate in the validation set was around 5.5%. When it predicted a 30%-39% chance, the actual rate was 32.6%. The area under the receiver operating characteristic curve was 0.7 in both the development and validation sets, indicating good discrimination.
The work grew out of an effort to implement the Society of Surgical Oncologists’ recommendation not to do routine sentinel node biopsies in clinically node negative, hormone receptor–positive invasive breast cancer in women over the age of 70 years, a recommendation the group made as part of its contribution to the Choosing Wisely campaign.
“After the guideline was released, we were sitting in the clinic thinking how to apply it to our patients,” lead investigator Jessemae Welsh, MD, a surgeon at the Mayo Clinic, said at the American Society of Breast Surgeons annual meeting.
The problem is that nodal positivity is important to know for other aspects of care, including regional nodal irradiation and duration of systemic hormone therapy, and axillary lymph node staging might still be indicated if older women are truly at high risk. “We [wanted] to develop a multivariate model that gives a precise estimate of nodal risk,” to help “patients and surgeons to decide together based on an individual risk” how best to proceed. Also, a prediction of low risk “can help reassure patients that they will do well without axillary surgery,” she said.
Mayo’s nomogram is unique in that it focuses specifically on women 70 years and older. Development of previous nomograms incorporated older women, but did not focus on them specifically, Dr. Welsh said.
Dr. Welsh said she had no relevant disclosures.
[email protected]
LAS VEGAS – In women aged 70 years or older with hormone receptor–positive invasive breast cancer, their tumor size, grade, and histology – but not human epidermal growth factor receptor–2 status – predicted nodal positivity, according to a retrospective analysis.
Investigators at the Mayo Clinic, Rochester, Minn., reviewed 52,532 women in the National Cancer Database from 2010 to 2013 who were at least 70 years old with hormone receptor–positive invasive breast cancer and clinically node negative disease, who had axillary surgery performed. Two-thirds of the cohort was used to identify risk factors, and the remaining third to validate them. About 16% in both groups had cancer in their axillary lymph nodes.
On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes. Although significant on univariate analysis, age (P = .57) and HER2 status (P = .32) fell out on multivariate analysis.
Nodal positivity was more than five times as likely with clinical T2 tumors, compared with T1a tumors, and far less likely for patients with invasive mucinous carcinoma than for those with invasive ductal carcinoma.
The team expects to release a nomogram for general use in clinical practice to predict the risk of positive nodes for various combinations of tumor size, grade, and histology in older women. When the model predicted a less than 10% chance of node positive disease, the actual rate in the validation set was around 5.5%. When it predicted a 30%-39% chance, the actual rate was 32.6%. The area under the receiver operating characteristic curve was 0.7 in both the development and validation sets, indicating good discrimination.
The work grew out of an effort to implement the Society of Surgical Oncologists’ recommendation not to do routine sentinel node biopsies in clinically node negative, hormone receptor–positive invasive breast cancer in women over the age of 70 years, a recommendation the group made as part of its contribution to the Choosing Wisely campaign.
“After the guideline was released, we were sitting in the clinic thinking how to apply it to our patients,” lead investigator Jessemae Welsh, MD, a surgeon at the Mayo Clinic, said at the American Society of Breast Surgeons annual meeting.
The problem is that nodal positivity is important to know for other aspects of care, including regional nodal irradiation and duration of systemic hormone therapy, and axillary lymph node staging might still be indicated if older women are truly at high risk. “We [wanted] to develop a multivariate model that gives a precise estimate of nodal risk,” to help “patients and surgeons to decide together based on an individual risk” how best to proceed. Also, a prediction of low risk “can help reassure patients that they will do well without axillary surgery,” she said.
Mayo’s nomogram is unique in that it focuses specifically on women 70 years and older. Development of previous nomograms incorporated older women, but did not focus on them specifically, Dr. Welsh said.
Dr. Welsh said she had no relevant disclosures.
[email protected]
AT ASBS 2017
Key clinical point:
Major finding: On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes.
Data source: An analysis of data from 52,532 women in the National Cancer Database during 2010-2013.
Disclosures: The lead investigator had no disclosures.
Forgo axillary dissection for single suspicious node on ultrasound
LAS VEGAS – About half of breast cancer patients without palpable lymphadenopathy but with preoperative ultrasound-guided, biopsy-proven axillary lymph node metastases have N1 disease, according to a review of 129 women.
Among the 30 women with a primary tumor 2 cm or smaller and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastases limited to the one lymph node, suggesting that such patients “may undergo ... sentinel lymph node biopsy” instead of a complete axillary lymph node dissection (ALND), the investigators concluded.
The problem that has come up in clinical practice is that axillary ultrasound is now a routine part of breast cancer workup, but the original trial didn’t address ultrasound, said senior investigator Rubie Sue Jackson, MD, at the annual meeting of the American Society of Breast Surgeons. As a result, “surgeons don’t know what to do with an ultrasound-detected suspicious node. I think a lot of surgeons, if they detect a positive lymph node by ultrasound, even if it’s nonpalpable, would not consider the patient a candidate for sentinel lymph node biopsy. Our data suggest that many of these patients are being overtreated if they have an upfront axillary lymph node dissection,” she said.
The 129 women had 1-3 suspicious, nonpalpable nodes on ultrasound that turned out to have metastatic disease on needle biopsy. They all had subsequent ALNDs.
On final pathology, 67 women (52%) had only one metastatic node. For those women, a sentinel lymph node biopsy was likely all that they required. “They probably did not benefit from having an ALND,” said Dr. Jackson, a breast surgeon at the Anne Arundel Medical Center in Annapolis, Md. The other 62 women (48%) had N2-3 disease.
A primary tumor sized 2 cm or smaller (P = .012); nonlobular histology (P = .013), and having only one suspicious nonpalpable node on ultrasound (P = .008) were all associated with NI disease. Of the women who met the criteria, only eight (27%) had N 2-3 disease (P = .007).
“Patients meeting the three criteria are particularly unlikely to have three or more positive sentinel lymph nodes” and require subsequent ALND. “You don’t need to do a complete axillary lymph node dissection upfront, as long as they are getting a lumpectomy and whole breast radiation,” Dr. Jackson said.
These days at Anne Arundel, “we do the axillary ultrasound, we biopsy the lymph node if it looks suspicious, but we don’t feel forced to do an ALND. If a patient has tumor biology that’s likely to be highly responsive, we do upfront chemotherapy. If they have luminal tumor biology that’s not going to be very responsive to neoadjuvant therapy,” with one or two suspicious nodes, “and they are planning to get breast conserving therapy, I would do a sentinel lymph node biopsy and x-ray the specimen to make sure that I’ve retrieved the clip,” she said.
Dr. Jackson didn’t have any disclosures, and there was no industry funding for the work.
[email protected]
LAS VEGAS – About half of breast cancer patients without palpable lymphadenopathy but with preoperative ultrasound-guided, biopsy-proven axillary lymph node metastases have N1 disease, according to a review of 129 women.
Among the 30 women with a primary tumor 2 cm or smaller and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastases limited to the one lymph node, suggesting that such patients “may undergo ... sentinel lymph node biopsy” instead of a complete axillary lymph node dissection (ALND), the investigators concluded.
The problem that has come up in clinical practice is that axillary ultrasound is now a routine part of breast cancer workup, but the original trial didn’t address ultrasound, said senior investigator Rubie Sue Jackson, MD, at the annual meeting of the American Society of Breast Surgeons. As a result, “surgeons don’t know what to do with an ultrasound-detected suspicious node. I think a lot of surgeons, if they detect a positive lymph node by ultrasound, even if it’s nonpalpable, would not consider the patient a candidate for sentinel lymph node biopsy. Our data suggest that many of these patients are being overtreated if they have an upfront axillary lymph node dissection,” she said.
The 129 women had 1-3 suspicious, nonpalpable nodes on ultrasound that turned out to have metastatic disease on needle biopsy. They all had subsequent ALNDs.
On final pathology, 67 women (52%) had only one metastatic node. For those women, a sentinel lymph node biopsy was likely all that they required. “They probably did not benefit from having an ALND,” said Dr. Jackson, a breast surgeon at the Anne Arundel Medical Center in Annapolis, Md. The other 62 women (48%) had N2-3 disease.
A primary tumor sized 2 cm or smaller (P = .012); nonlobular histology (P = .013), and having only one suspicious nonpalpable node on ultrasound (P = .008) were all associated with NI disease. Of the women who met the criteria, only eight (27%) had N 2-3 disease (P = .007).
“Patients meeting the three criteria are particularly unlikely to have three or more positive sentinel lymph nodes” and require subsequent ALND. “You don’t need to do a complete axillary lymph node dissection upfront, as long as they are getting a lumpectomy and whole breast radiation,” Dr. Jackson said.
These days at Anne Arundel, “we do the axillary ultrasound, we biopsy the lymph node if it looks suspicious, but we don’t feel forced to do an ALND. If a patient has tumor biology that’s likely to be highly responsive, we do upfront chemotherapy. If they have luminal tumor biology that’s not going to be very responsive to neoadjuvant therapy,” with one or two suspicious nodes, “and they are planning to get breast conserving therapy, I would do a sentinel lymph node biopsy and x-ray the specimen to make sure that I’ve retrieved the clip,” she said.
Dr. Jackson didn’t have any disclosures, and there was no industry funding for the work.
[email protected]
LAS VEGAS – About half of breast cancer patients without palpable lymphadenopathy but with preoperative ultrasound-guided, biopsy-proven axillary lymph node metastases have N1 disease, according to a review of 129 women.
Among the 30 women with a primary tumor 2 cm or smaller and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastases limited to the one lymph node, suggesting that such patients “may undergo ... sentinel lymph node biopsy” instead of a complete axillary lymph node dissection (ALND), the investigators concluded.
The problem that has come up in clinical practice is that axillary ultrasound is now a routine part of breast cancer workup, but the original trial didn’t address ultrasound, said senior investigator Rubie Sue Jackson, MD, at the annual meeting of the American Society of Breast Surgeons. As a result, “surgeons don’t know what to do with an ultrasound-detected suspicious node. I think a lot of surgeons, if they detect a positive lymph node by ultrasound, even if it’s nonpalpable, would not consider the patient a candidate for sentinel lymph node biopsy. Our data suggest that many of these patients are being overtreated if they have an upfront axillary lymph node dissection,” she said.
The 129 women had 1-3 suspicious, nonpalpable nodes on ultrasound that turned out to have metastatic disease on needle biopsy. They all had subsequent ALNDs.
On final pathology, 67 women (52%) had only one metastatic node. For those women, a sentinel lymph node biopsy was likely all that they required. “They probably did not benefit from having an ALND,” said Dr. Jackson, a breast surgeon at the Anne Arundel Medical Center in Annapolis, Md. The other 62 women (48%) had N2-3 disease.
A primary tumor sized 2 cm or smaller (P = .012); nonlobular histology (P = .013), and having only one suspicious nonpalpable node on ultrasound (P = .008) were all associated with NI disease. Of the women who met the criteria, only eight (27%) had N 2-3 disease (P = .007).
“Patients meeting the three criteria are particularly unlikely to have three or more positive sentinel lymph nodes” and require subsequent ALND. “You don’t need to do a complete axillary lymph node dissection upfront, as long as they are getting a lumpectomy and whole breast radiation,” Dr. Jackson said.
These days at Anne Arundel, “we do the axillary ultrasound, we biopsy the lymph node if it looks suspicious, but we don’t feel forced to do an ALND. If a patient has tumor biology that’s likely to be highly responsive, we do upfront chemotherapy. If they have luminal tumor biology that’s not going to be very responsive to neoadjuvant therapy,” with one or two suspicious nodes, “and they are planning to get breast conserving therapy, I would do a sentinel lymph node biopsy and x-ray the specimen to make sure that I’ve retrieved the clip,” she said.
Dr. Jackson didn’t have any disclosures, and there was no industry funding for the work.
[email protected]
AT ASBS 2017
Key clinical point:
Major finding: Among the 30 women with tumors 2 cm or smaller, and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastasis limited to the one lymph node.
Data source: A review of 129 women with breast cancer.
Disclosures: There was no industry funding, and the senior investigator had no disclosures.
Omitting ALND in some breast cancer patients may be the right choice
PHILADELPHIA – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) has been established for patients with cT1-2N0 cancer that are found to have one or two metastatic sentinel lymph nodes who undergo breast conservation therapy, but questions regarding the role of regional radiation have persisted.
This issue is addressed by the results of a large, prospective, 5+ year study at Memorial Sloan Kettering Cancer Center which confirmed the safety of omitting axillary lymph node dissection and suggested that regional radiation provides minimal benefit.
Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.
Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.
Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.
In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.
Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.
“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).
The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.
“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.
In his comments, Armando Giuliano, MD, of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial, said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that nodal irradiation provides very little benefit to this selected group of patients.”
The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial,” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”
Dr. Morrow and Dr. Giuliano reported no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.
PHILADELPHIA – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) has been established for patients with cT1-2N0 cancer that are found to have one or two metastatic sentinel lymph nodes who undergo breast conservation therapy, but questions regarding the role of regional radiation have persisted.
This issue is addressed by the results of a large, prospective, 5+ year study at Memorial Sloan Kettering Cancer Center which confirmed the safety of omitting axillary lymph node dissection and suggested that regional radiation provides minimal benefit.
Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.
Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.
Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.
In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.
Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.
“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).
The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.
“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.
In his comments, Armando Giuliano, MD, of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial, said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that nodal irradiation provides very little benefit to this selected group of patients.”
The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial,” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”
Dr. Morrow and Dr. Giuliano reported no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.
PHILADELPHIA – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) has been established for patients with cT1-2N0 cancer that are found to have one or two metastatic sentinel lymph nodes who undergo breast conservation therapy, but questions regarding the role of regional radiation have persisted.
This issue is addressed by the results of a large, prospective, 5+ year study at Memorial Sloan Kettering Cancer Center which confirmed the safety of omitting axillary lymph node dissection and suggested that regional radiation provides minimal benefit.
Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.
Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.
Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.
In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.
Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.
“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).
The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.
“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.
In his comments, Armando Giuliano, MD, of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial, said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that nodal irradiation provides very little benefit to this selected group of patients.”
The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial,” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”
Dr. Morrow and Dr. Giuliano reported no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.
AT THE ANNUAL ASA MEETING
More early-stage cancer diagnosis since ACA implementation
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: The proportion of cancers that were stage I when diagnosed increased by about 1% after ACA implementation for breast, cervical, lung, and colorectal cancer, while it decreased by 1% for prostate cancer.
Data source: A cohort study of 272,656 patients with these five cancers from the National Cancer Database.
Disclosures: Dr. Han reported that she had no disclosures.
Three drug combinations represent next level for high-risk breast cancer
BRUSSELS – Now that dual combinations of targeted breast cancer drugs are standard treatment, researchers see up-front triple drug combinations as the next treatment frontier.
“Doublets are simply not enough,” Dejan Juric, MD, said at a breast cancer conference sponsored by the European Society of Medical Oncology. Triple-drug combinations offer the possibility of substantially-reduced rates of resistance development and the possibility of reducing dosages to improve tolerability.
One way to leverage the potential of a triple regimen is to target all three drugs at the same oncogenic pathway. “If we target a pathway with multiple drugs do we still need the maximally-tolerated dose of each? Clearly no,” said René Bernards, PhD, a professor at the Netherlands Cancer Institute in Amsterdam.
Dr. Bernards said he has as-yet unpublished evidence that individual-drug dosages can be cut when using a combination regimen that joins treatments targeted to the sequential signaling steps of Raf, MEK, and ERK in a key signaling cascade tied to the epidermal growth factor receptor (BBA Mol Cell Res. 2007 Aug;1773[8]:1263-84). “We now have drugs for all these [targets]. You can use 10% of the effective dose of each of these drugs and get complete inhibition of the pathway and not make cells resistant to these low-doses,” he declared.
Having drugs that work well together is critical, agreed Dr. Juric. “We need to keep searching for drugs where you can achieve nice inhibition by the triplet.” The goal is to “completely shut down a pathway,” he said. While “upfront combination is always superior to a sequential strategy, we hope that a new combination is not just more hits at the goal but a new quality.” The conventional concept of first-line, second-line, and third-line treatments is an “obstacle” to development of the most rational combinations.
A challenge when testing a triple regimen as first-line treatment is deciding which patients to target, as some hormone-receptor positive patients can do well on just an aromatase inhibitor.
“I don’t know which patients will do well on a single agent and who will need a combination,” said Dr. Juric. Given that uncertainty, his priorities are testing combination regimens that are both tolerable and cost effective. He also stressed the need to “better understand the tumor we are dealing with, using blood and biopsies, and use an adaptive approach” based on each tumor’s combination of characteristics.
As long as tolerability is possible, preclinical models suggest that the biggest impact from combination regimens comes in treatment naive patients. That would mean targeting patients with high-risk, estrogen–receptor positive breast cancer “where we know the risk continues for 20, 30 years and the long-term prognosis for relapse is very poor,” said Nicholas Turner, MD, a molecular oncologist at the Institute of Cancer Research and the Royal Marsden Hospital, both in London. “Perhaps a triple combination, if tolerable, would have the most potential to change the prognosis of these patients.”
Dr. Juric has been a consultant to Eisai, EMD, Novartis, and Serono. Dr. Bernards owns a portion of Agendia, a company that markets a breast cancer genetic test he codeveloped. Dr. Turner has received honoraria from Lilly, Novartis, Pfizer, and Roche.
[email protected]
On Twitter @mitchelzoler
BRUSSELS – Now that dual combinations of targeted breast cancer drugs are standard treatment, researchers see up-front triple drug combinations as the next treatment frontier.
“Doublets are simply not enough,” Dejan Juric, MD, said at a breast cancer conference sponsored by the European Society of Medical Oncology. Triple-drug combinations offer the possibility of substantially-reduced rates of resistance development and the possibility of reducing dosages to improve tolerability.
One way to leverage the potential of a triple regimen is to target all three drugs at the same oncogenic pathway. “If we target a pathway with multiple drugs do we still need the maximally-tolerated dose of each? Clearly no,” said René Bernards, PhD, a professor at the Netherlands Cancer Institute in Amsterdam.
Dr. Bernards said he has as-yet unpublished evidence that individual-drug dosages can be cut when using a combination regimen that joins treatments targeted to the sequential signaling steps of Raf, MEK, and ERK in a key signaling cascade tied to the epidermal growth factor receptor (BBA Mol Cell Res. 2007 Aug;1773[8]:1263-84). “We now have drugs for all these [targets]. You can use 10% of the effective dose of each of these drugs and get complete inhibition of the pathway and not make cells resistant to these low-doses,” he declared.
Having drugs that work well together is critical, agreed Dr. Juric. “We need to keep searching for drugs where you can achieve nice inhibition by the triplet.” The goal is to “completely shut down a pathway,” he said. While “upfront combination is always superior to a sequential strategy, we hope that a new combination is not just more hits at the goal but a new quality.” The conventional concept of first-line, second-line, and third-line treatments is an “obstacle” to development of the most rational combinations.
A challenge when testing a triple regimen as first-line treatment is deciding which patients to target, as some hormone-receptor positive patients can do well on just an aromatase inhibitor.
“I don’t know which patients will do well on a single agent and who will need a combination,” said Dr. Juric. Given that uncertainty, his priorities are testing combination regimens that are both tolerable and cost effective. He also stressed the need to “better understand the tumor we are dealing with, using blood and biopsies, and use an adaptive approach” based on each tumor’s combination of characteristics.
As long as tolerability is possible, preclinical models suggest that the biggest impact from combination regimens comes in treatment naive patients. That would mean targeting patients with high-risk, estrogen–receptor positive breast cancer “where we know the risk continues for 20, 30 years and the long-term prognosis for relapse is very poor,” said Nicholas Turner, MD, a molecular oncologist at the Institute of Cancer Research and the Royal Marsden Hospital, both in London. “Perhaps a triple combination, if tolerable, would have the most potential to change the prognosis of these patients.”
Dr. Juric has been a consultant to Eisai, EMD, Novartis, and Serono. Dr. Bernards owns a portion of Agendia, a company that markets a breast cancer genetic test he codeveloped. Dr. Turner has received honoraria from Lilly, Novartis, Pfizer, and Roche.
[email protected]
On Twitter @mitchelzoler
BRUSSELS – Now that dual combinations of targeted breast cancer drugs are standard treatment, researchers see up-front triple drug combinations as the next treatment frontier.
“Doublets are simply not enough,” Dejan Juric, MD, said at a breast cancer conference sponsored by the European Society of Medical Oncology. Triple-drug combinations offer the possibility of substantially-reduced rates of resistance development and the possibility of reducing dosages to improve tolerability.
One way to leverage the potential of a triple regimen is to target all three drugs at the same oncogenic pathway. “If we target a pathway with multiple drugs do we still need the maximally-tolerated dose of each? Clearly no,” said René Bernards, PhD, a professor at the Netherlands Cancer Institute in Amsterdam.
Dr. Bernards said he has as-yet unpublished evidence that individual-drug dosages can be cut when using a combination regimen that joins treatments targeted to the sequential signaling steps of Raf, MEK, and ERK in a key signaling cascade tied to the epidermal growth factor receptor (BBA Mol Cell Res. 2007 Aug;1773[8]:1263-84). “We now have drugs for all these [targets]. You can use 10% of the effective dose of each of these drugs and get complete inhibition of the pathway and not make cells resistant to these low-doses,” he declared.
Having drugs that work well together is critical, agreed Dr. Juric. “We need to keep searching for drugs where you can achieve nice inhibition by the triplet.” The goal is to “completely shut down a pathway,” he said. While “upfront combination is always superior to a sequential strategy, we hope that a new combination is not just more hits at the goal but a new quality.” The conventional concept of first-line, second-line, and third-line treatments is an “obstacle” to development of the most rational combinations.
A challenge when testing a triple regimen as first-line treatment is deciding which patients to target, as some hormone-receptor positive patients can do well on just an aromatase inhibitor.
“I don’t know which patients will do well on a single agent and who will need a combination,” said Dr. Juric. Given that uncertainty, his priorities are testing combination regimens that are both tolerable and cost effective. He also stressed the need to “better understand the tumor we are dealing with, using blood and biopsies, and use an adaptive approach” based on each tumor’s combination of characteristics.
As long as tolerability is possible, preclinical models suggest that the biggest impact from combination regimens comes in treatment naive patients. That would mean targeting patients with high-risk, estrogen–receptor positive breast cancer “where we know the risk continues for 20, 30 years and the long-term prognosis for relapse is very poor,” said Nicholas Turner, MD, a molecular oncologist at the Institute of Cancer Research and the Royal Marsden Hospital, both in London. “Perhaps a triple combination, if tolerable, would have the most potential to change the prognosis of these patients.”
Dr. Juric has been a consultant to Eisai, EMD, Novartis, and Serono. Dr. Bernards owns a portion of Agendia, a company that markets a breast cancer genetic test he codeveloped. Dr. Turner has received honoraria from Lilly, Novartis, Pfizer, and Roche.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM IMPAKT 2017
Educate patients about dense breasts and cancer risk
Monica Saini, MD, a radiologist in Santa Fe, New Mexico, and JoAnn Pushkin, executive director of the nonprofit educational website DenseBreast-info.org, engaged ObGyn attendees on “Breast density: Why it matters and what to do” at the American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Clinical and Scientific Meeting (May 6–9, 2017) in San Diego, California. The program was sponsored by GE Healthcare.
DENSE BREASTS ARE A RISK FACTOR FOR CANCER
Breast density is the second largest risk factor for breast cancer after radiation treatment to the chest, so it is important to identify patients with dense breasts, according to Dr. Saini. The American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classifies breast density into 4 groups: 1) almost entirely fatty, 2) scattered fibroglandular densities, 3) heterogeneously dense, and 4) extremely dense. A woman whose mammograms show heterogeneously dense or extremely dense breasts is considered to have “dense breasts.”
Cancer is often difficult to identify with mammography in dense breasts because masses or lumps appear as white on a white (dense tissue) background; by contrast, a tumor in a nondense (fatty) breast would appear as white on a dark, fatty tissue background. Approximately one-third of cancers in dense breasts have a delayed diagnosis on mammography, and 70% of cancers occur in dense breasts, said Dr. Saini.
Having dense breasts is not an abnormal condition, however, and is actually common—about 40% of women aged 40 or older have dense breasts.
Supplement mammography with other screening modalities
While screening mammograms can save lives, mammography should not be viewed as a one-size-fits-all modality. Screening for breast cancer should be personalized, based on, among other factors, a woman’s personal and family history, age, genetic risk, lifestyle factors, and breast density.
Key point. Women with dense breasts should continue to have screening mammograms. In addition, mammography for these patients should be supplemented with other technologies, such as 3D mammography (digital tomosynthesis), handheld ultrasound, or automated breast ultrasound (ABUS). In women at higher risk (presence of BRCA1 or BRCA2 gene mutation, strong family history of breast cancer, or radiation treatment to the chest) magnetic resonance imaging (MRI) may be considered.
Data on adjunct screening modalities. Dr. Saini discussed the results of the ASTOUND trial, a prospective multicenter study that compared ultrasound and tomosynthesis for the detection of breast cancer in mammography-negative dense breasts.1 Among the 3,231 asymptomatic women included in the trial, 13 breast cancers were detected with tomosynthesis (incremental cancer detection rate [CDR], 4 per 1,000 screens; 95% confidence interval [CI], 1.8–6.2) and 23 were detected with ultrasound (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.4–10.0), P = .006. There were 107 false-positive results: 53 with tomosynthesis and 65 with ultrasound, a difference that was not statistically significant. The study authors noted that while ultrasound had better incremental breast cancer detection than tomosynthesis, and at a similar false-positive recall rate, tomosynthesis did detect more than half of the additional breast cancers in these women.1
Make screening easier for the patient
Dr. Saini noted that for women with dense breasts, performing mammography and adjunctive screening at the same visit is convenient for the patient. Physicians can also write prescriptions for follow-up based on density findings, for example, “3D mammography if available, if dense, order ultrasound.”
Read how to answer patient questions about breast density
ARE YOU READY TO ANSWER PATIENT QUESTIONS ABOUT BREAST DENSITY?
That is the question JoAnn Pushkin, executive director of DenseBreast-info.org, asked in her presentation. You should discuss with patients exactly what it means to have dense breasts, breast density as an independent risk factor for cancer, the breast imaging technologies available for screening (mammography, tomosynthesis, ultrasound, contrast-enhanced MRI), the risks and benefits of each screening modality, and surveillance intervals for women with dense breasts. Good communication with the patient’s radiology team assists in formulating an individualized screening strategy.
Patients may have concerns about the information provided—or not provided—in their state’s breast density notification letter after a mammogram. Currently, 31 states mandate some type of breast density notification, while 4 states have efforts for density reporting or education that do not require notification. The information given to patients and how they will be informed varies by state. Some states, for example, require that patients who have heterogeneously or extremely dense breasts be informed of this by letter, while other states require that all patients receive the same notification with information about dense breasts but does not tell them whether or not they have dense breasts.
A go-to resource for ObGyns and patients
The website of the nonprofit DenseBreast-Info.org (http://densebreast-info.org/), co-founded by Wendie Berg, MD, PhD, who serves as Chief Scientific Advisor to the organization and is Professor of Radiology at the University of Pittsburgh School of Medicine/Magee-Women’s Hospital of UPMC, provides an interactive US map that features state-by-state breast density reporting guidelines so you can stay up-to-date on notification legislation in your area.
Sections for patients offer comprehensive and clearly written information on categories of breast density, a patient risk checklist, screening test descriptions, frequently asked questions, educational videos, and a patient brochure in English and Spanish.
For health care providers, resources include:
- a screening decision support tool flowchart to help assess which patients need more screening
- a table summarizing the cancer detection rates for mammography alone and mammography plus another screening modality (tomosynthesis, ultrasound, MRI)
- a comparison of breast cancer screening guidelines from various medical societies, including the American College of Radiology/Society of Breast Imaging, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force.
A special section covers screening technology, and each page includes descriptions, benefits, and considerations for use. Photos of the equipment and images of breast scans with explanatory captions enhance understanding.
Screening for high-risk women
Ms. Pushkin noted that for high-risk patients with dense breasts, mammography plus MRI annually would be an appropriate option.
- Tagliafico AS, Calabrese M, Mariscotti G, et al. Adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts: interim report of a prospective comparative trial [published online ahead of print March 9, 2015]. J Clin Oncol. doi:10.1200/JCO.2015.63.4147.
Monica Saini, MD, a radiologist in Santa Fe, New Mexico, and JoAnn Pushkin, executive director of the nonprofit educational website DenseBreast-info.org, engaged ObGyn attendees on “Breast density: Why it matters and what to do” at the American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Clinical and Scientific Meeting (May 6–9, 2017) in San Diego, California. The program was sponsored by GE Healthcare.
DENSE BREASTS ARE A RISK FACTOR FOR CANCER
Breast density is the second largest risk factor for breast cancer after radiation treatment to the chest, so it is important to identify patients with dense breasts, according to Dr. Saini. The American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classifies breast density into 4 groups: 1) almost entirely fatty, 2) scattered fibroglandular densities, 3) heterogeneously dense, and 4) extremely dense. A woman whose mammograms show heterogeneously dense or extremely dense breasts is considered to have “dense breasts.”
Cancer is often difficult to identify with mammography in dense breasts because masses or lumps appear as white on a white (dense tissue) background; by contrast, a tumor in a nondense (fatty) breast would appear as white on a dark, fatty tissue background. Approximately one-third of cancers in dense breasts have a delayed diagnosis on mammography, and 70% of cancers occur in dense breasts, said Dr. Saini.
Having dense breasts is not an abnormal condition, however, and is actually common—about 40% of women aged 40 or older have dense breasts.
Supplement mammography with other screening modalities
While screening mammograms can save lives, mammography should not be viewed as a one-size-fits-all modality. Screening for breast cancer should be personalized, based on, among other factors, a woman’s personal and family history, age, genetic risk, lifestyle factors, and breast density.
Key point. Women with dense breasts should continue to have screening mammograms. In addition, mammography for these patients should be supplemented with other technologies, such as 3D mammography (digital tomosynthesis), handheld ultrasound, or automated breast ultrasound (ABUS). In women at higher risk (presence of BRCA1 or BRCA2 gene mutation, strong family history of breast cancer, or radiation treatment to the chest) magnetic resonance imaging (MRI) may be considered.
Data on adjunct screening modalities. Dr. Saini discussed the results of the ASTOUND trial, a prospective multicenter study that compared ultrasound and tomosynthesis for the detection of breast cancer in mammography-negative dense breasts.1 Among the 3,231 asymptomatic women included in the trial, 13 breast cancers were detected with tomosynthesis (incremental cancer detection rate [CDR], 4 per 1,000 screens; 95% confidence interval [CI], 1.8–6.2) and 23 were detected with ultrasound (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.4–10.0), P = .006. There were 107 false-positive results: 53 with tomosynthesis and 65 with ultrasound, a difference that was not statistically significant. The study authors noted that while ultrasound had better incremental breast cancer detection than tomosynthesis, and at a similar false-positive recall rate, tomosynthesis did detect more than half of the additional breast cancers in these women.1
Make screening easier for the patient
Dr. Saini noted that for women with dense breasts, performing mammography and adjunctive screening at the same visit is convenient for the patient. Physicians can also write prescriptions for follow-up based on density findings, for example, “3D mammography if available, if dense, order ultrasound.”
Read how to answer patient questions about breast density
ARE YOU READY TO ANSWER PATIENT QUESTIONS ABOUT BREAST DENSITY?
That is the question JoAnn Pushkin, executive director of DenseBreast-info.org, asked in her presentation. You should discuss with patients exactly what it means to have dense breasts, breast density as an independent risk factor for cancer, the breast imaging technologies available for screening (mammography, tomosynthesis, ultrasound, contrast-enhanced MRI), the risks and benefits of each screening modality, and surveillance intervals for women with dense breasts. Good communication with the patient’s radiology team assists in formulating an individualized screening strategy.
Patients may have concerns about the information provided—or not provided—in their state’s breast density notification letter after a mammogram. Currently, 31 states mandate some type of breast density notification, while 4 states have efforts for density reporting or education that do not require notification. The information given to patients and how they will be informed varies by state. Some states, for example, require that patients who have heterogeneously or extremely dense breasts be informed of this by letter, while other states require that all patients receive the same notification with information about dense breasts but does not tell them whether or not they have dense breasts.
A go-to resource for ObGyns and patients
The website of the nonprofit DenseBreast-Info.org (http://densebreast-info.org/), co-founded by Wendie Berg, MD, PhD, who serves as Chief Scientific Advisor to the organization and is Professor of Radiology at the University of Pittsburgh School of Medicine/Magee-Women’s Hospital of UPMC, provides an interactive US map that features state-by-state breast density reporting guidelines so you can stay up-to-date on notification legislation in your area.
Sections for patients offer comprehensive and clearly written information on categories of breast density, a patient risk checklist, screening test descriptions, frequently asked questions, educational videos, and a patient brochure in English and Spanish.
For health care providers, resources include:
- a screening decision support tool flowchart to help assess which patients need more screening
- a table summarizing the cancer detection rates for mammography alone and mammography plus another screening modality (tomosynthesis, ultrasound, MRI)
- a comparison of breast cancer screening guidelines from various medical societies, including the American College of Radiology/Society of Breast Imaging, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force.
A special section covers screening technology, and each page includes descriptions, benefits, and considerations for use. Photos of the equipment and images of breast scans with explanatory captions enhance understanding.
Screening for high-risk women
Ms. Pushkin noted that for high-risk patients with dense breasts, mammography plus MRI annually would be an appropriate option.
Monica Saini, MD, a radiologist in Santa Fe, New Mexico, and JoAnn Pushkin, executive director of the nonprofit educational website DenseBreast-info.org, engaged ObGyn attendees on “Breast density: Why it matters and what to do” at the American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Clinical and Scientific Meeting (May 6–9, 2017) in San Diego, California. The program was sponsored by GE Healthcare.
DENSE BREASTS ARE A RISK FACTOR FOR CANCER
Breast density is the second largest risk factor for breast cancer after radiation treatment to the chest, so it is important to identify patients with dense breasts, according to Dr. Saini. The American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classifies breast density into 4 groups: 1) almost entirely fatty, 2) scattered fibroglandular densities, 3) heterogeneously dense, and 4) extremely dense. A woman whose mammograms show heterogeneously dense or extremely dense breasts is considered to have “dense breasts.”
Cancer is often difficult to identify with mammography in dense breasts because masses or lumps appear as white on a white (dense tissue) background; by contrast, a tumor in a nondense (fatty) breast would appear as white on a dark, fatty tissue background. Approximately one-third of cancers in dense breasts have a delayed diagnosis on mammography, and 70% of cancers occur in dense breasts, said Dr. Saini.
Having dense breasts is not an abnormal condition, however, and is actually common—about 40% of women aged 40 or older have dense breasts.
Supplement mammography with other screening modalities
While screening mammograms can save lives, mammography should not be viewed as a one-size-fits-all modality. Screening for breast cancer should be personalized, based on, among other factors, a woman’s personal and family history, age, genetic risk, lifestyle factors, and breast density.
Key point. Women with dense breasts should continue to have screening mammograms. In addition, mammography for these patients should be supplemented with other technologies, such as 3D mammography (digital tomosynthesis), handheld ultrasound, or automated breast ultrasound (ABUS). In women at higher risk (presence of BRCA1 or BRCA2 gene mutation, strong family history of breast cancer, or radiation treatment to the chest) magnetic resonance imaging (MRI) may be considered.
Data on adjunct screening modalities. Dr. Saini discussed the results of the ASTOUND trial, a prospective multicenter study that compared ultrasound and tomosynthesis for the detection of breast cancer in mammography-negative dense breasts.1 Among the 3,231 asymptomatic women included in the trial, 13 breast cancers were detected with tomosynthesis (incremental cancer detection rate [CDR], 4 per 1,000 screens; 95% confidence interval [CI], 1.8–6.2) and 23 were detected with ultrasound (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.4–10.0), P = .006. There were 107 false-positive results: 53 with tomosynthesis and 65 with ultrasound, a difference that was not statistically significant. The study authors noted that while ultrasound had better incremental breast cancer detection than tomosynthesis, and at a similar false-positive recall rate, tomosynthesis did detect more than half of the additional breast cancers in these women.1
Make screening easier for the patient
Dr. Saini noted that for women with dense breasts, performing mammography and adjunctive screening at the same visit is convenient for the patient. Physicians can also write prescriptions for follow-up based on density findings, for example, “3D mammography if available, if dense, order ultrasound.”
Read how to answer patient questions about breast density
ARE YOU READY TO ANSWER PATIENT QUESTIONS ABOUT BREAST DENSITY?
That is the question JoAnn Pushkin, executive director of DenseBreast-info.org, asked in her presentation. You should discuss with patients exactly what it means to have dense breasts, breast density as an independent risk factor for cancer, the breast imaging technologies available for screening (mammography, tomosynthesis, ultrasound, contrast-enhanced MRI), the risks and benefits of each screening modality, and surveillance intervals for women with dense breasts. Good communication with the patient’s radiology team assists in formulating an individualized screening strategy.
Patients may have concerns about the information provided—or not provided—in their state’s breast density notification letter after a mammogram. Currently, 31 states mandate some type of breast density notification, while 4 states have efforts for density reporting or education that do not require notification. The information given to patients and how they will be informed varies by state. Some states, for example, require that patients who have heterogeneously or extremely dense breasts be informed of this by letter, while other states require that all patients receive the same notification with information about dense breasts but does not tell them whether or not they have dense breasts.
A go-to resource for ObGyns and patients
The website of the nonprofit DenseBreast-Info.org (http://densebreast-info.org/), co-founded by Wendie Berg, MD, PhD, who serves as Chief Scientific Advisor to the organization and is Professor of Radiology at the University of Pittsburgh School of Medicine/Magee-Women’s Hospital of UPMC, provides an interactive US map that features state-by-state breast density reporting guidelines so you can stay up-to-date on notification legislation in your area.
Sections for patients offer comprehensive and clearly written information on categories of breast density, a patient risk checklist, screening test descriptions, frequently asked questions, educational videos, and a patient brochure in English and Spanish.
For health care providers, resources include:
- a screening decision support tool flowchart to help assess which patients need more screening
- a table summarizing the cancer detection rates for mammography alone and mammography plus another screening modality (tomosynthesis, ultrasound, MRI)
- a comparison of breast cancer screening guidelines from various medical societies, including the American College of Radiology/Society of Breast Imaging, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force.
A special section covers screening technology, and each page includes descriptions, benefits, and considerations for use. Photos of the equipment and images of breast scans with explanatory captions enhance understanding.
Screening for high-risk women
Ms. Pushkin noted that for high-risk patients with dense breasts, mammography plus MRI annually would be an appropriate option.
- Tagliafico AS, Calabrese M, Mariscotti G, et al. Adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts: interim report of a prospective comparative trial [published online ahead of print March 9, 2015]. J Clin Oncol. doi:10.1200/JCO.2015.63.4147.
- Tagliafico AS, Calabrese M, Mariscotti G, et al. Adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts: interim report of a prospective comparative trial [published online ahead of print March 9, 2015]. J Clin Oncol. doi:10.1200/JCO.2015.63.4147.
