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Gene signature found similarly prognostic in ILC and IDC
ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.
“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”
With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.
With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.
The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.
“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”
It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
Prognostic, but predictive?
“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.
Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.
These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.
“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
Study details
Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.
MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.
Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.
The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).
The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.
The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.
ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.
“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”
With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.
With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.
The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.
“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”
It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
Prognostic, but predictive?
“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.
Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.
These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.
“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
Study details
Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.
MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.
Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.
The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).
The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.
The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.
ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.
“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”
With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.
With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.
The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.
“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”
It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
Prognostic, but predictive?
“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.
Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.
These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.
“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
Study details
Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.
MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.
Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.
The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).
The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.
The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.
FROM EBCC-12 VIRTUAL CONFERENCE
Study advances personalized treatment for older breast cancer patients
Findings from the study were reported at the 12th European Breast Cancer Conference.
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.
Cluster-randomized controlled trial
In the cluster-randomized controlled trial, researchers compared a decision support tool to usual care. The tool was developed using U.K. registry data from almost 30,000 older women and input from women in this age group on their preferred format and method of presentation, according to Dr. Wyld.
The tool consists of an algorithm available to clinicians online (for input of tumor stage and biology, comorbidities, and functional status) plus a booklet and outcome sheets for patients to take home after discussions that can be personalized to their particulars.
Intention-to-treat analyses were based on 1,339 patients with operable breast cancer, 1,161 of whom had ER+ disease. Per-protocol analyses were based on the subset of 449 patients who were offered a choice between surgery and primary endocrine therapy, presumably because they were less fit and frailer.
Results showed that, at 6 months, mean scores for global quality of life on the EORTC questionnaire did not differ between decision support and usual care in the intention-to-treat population (69.0 vs. 68.9; P = .900), but scores were more favorable with decision support in the per-protocol population (70.7 vs. 66.8; P = .044).
The tool also altered treatment choices, with a larger share of ER+ patients choosing primary endocrine therapy (21.0% vs. 15.4%; P = .029) but still having similar disease outcomes.
Although ER+ patients in the decision support group more often selected primary endocrine therapy, at a median follow-up of 36 months, the groups did not differ significantly on overall survival, cause-specific survival, or time to recurrence in either intention-to-treat or per-protocol analyses.
Larger shares of women in the decision support group reported that they had adequate knowledge about the treatment options available to them (94% vs. 74%), were aware of the advantages and disadvantages of each option (91% vs. 76%), knew which option they preferred (96% vs. 91%), and were ready to make a decision (99% vs. 90%).
Applying results to practice
“Most women over the age of 70 are relatively fit, and the aim should be to treat them with surgery,” Dr. Wyld said. “For the less fit, a point is reached where the oncology benefits of surgery disappear and surgery may just cause harm. This threshold appears to be for women in their mid-80s with moderate to poor health.”
“Use of the Age Gap online tool may enhance shared decision-making for these women while increasing knowledge. And whilst it does seem to increase the use of primary endocrine therapy, this does not seem to have an adverse impact on survival at 36 months of follow-up,” she added.
“The study by Dr. Wyld and colleagues adds to the available literature regarding the scenarios in which some treatments may be omitted without impacting overall survival in older women with breast cancer,” Lesly A. Dossett, MD, of Michigan Medicine in Ann Arbor, commented in an interview.
In her own practice, Dr. Dossett emphasizes the generally favorable prognosis for older women with hormone receptor–positive breast cancer, she said. However, tools that help communicate risk and clarify the value of various therapies are welcome.
“The decision support tool appears to be a promising tool in helping to avoid treatments that are unlikely to benefit older women with breast cancer,” Dr. Dossett said. “The results will be widely applicable, as there is growing recognition that this patient population is at risk for overtreatment.”
The study was funded by the U.K. National Institute for Health Research programme grant for applied research. Dr. Wyld and Dr. Dossett said they had no relevant conflicts of interest.
SOURCES: Wyld L et al. EBCC-12 Virtual Congress. Abstract 8A and Abstract 8B.
Findings from the study were reported at the 12th European Breast Cancer Conference.
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.
Cluster-randomized controlled trial
In the cluster-randomized controlled trial, researchers compared a decision support tool to usual care. The tool was developed using U.K. registry data from almost 30,000 older women and input from women in this age group on their preferred format and method of presentation, according to Dr. Wyld.
The tool consists of an algorithm available to clinicians online (for input of tumor stage and biology, comorbidities, and functional status) plus a booklet and outcome sheets for patients to take home after discussions that can be personalized to their particulars.
Intention-to-treat analyses were based on 1,339 patients with operable breast cancer, 1,161 of whom had ER+ disease. Per-protocol analyses were based on the subset of 449 patients who were offered a choice between surgery and primary endocrine therapy, presumably because they were less fit and frailer.
Results showed that, at 6 months, mean scores for global quality of life on the EORTC questionnaire did not differ between decision support and usual care in the intention-to-treat population (69.0 vs. 68.9; P = .900), but scores were more favorable with decision support in the per-protocol population (70.7 vs. 66.8; P = .044).
The tool also altered treatment choices, with a larger share of ER+ patients choosing primary endocrine therapy (21.0% vs. 15.4%; P = .029) but still having similar disease outcomes.
Although ER+ patients in the decision support group more often selected primary endocrine therapy, at a median follow-up of 36 months, the groups did not differ significantly on overall survival, cause-specific survival, or time to recurrence in either intention-to-treat or per-protocol analyses.
Larger shares of women in the decision support group reported that they had adequate knowledge about the treatment options available to them (94% vs. 74%), were aware of the advantages and disadvantages of each option (91% vs. 76%), knew which option they preferred (96% vs. 91%), and were ready to make a decision (99% vs. 90%).
Applying results to practice
“Most women over the age of 70 are relatively fit, and the aim should be to treat them with surgery,” Dr. Wyld said. “For the less fit, a point is reached where the oncology benefits of surgery disappear and surgery may just cause harm. This threshold appears to be for women in their mid-80s with moderate to poor health.”
“Use of the Age Gap online tool may enhance shared decision-making for these women while increasing knowledge. And whilst it does seem to increase the use of primary endocrine therapy, this does not seem to have an adverse impact on survival at 36 months of follow-up,” she added.
“The study by Dr. Wyld and colleagues adds to the available literature regarding the scenarios in which some treatments may be omitted without impacting overall survival in older women with breast cancer,” Lesly A. Dossett, MD, of Michigan Medicine in Ann Arbor, commented in an interview.
In her own practice, Dr. Dossett emphasizes the generally favorable prognosis for older women with hormone receptor–positive breast cancer, she said. However, tools that help communicate risk and clarify the value of various therapies are welcome.
“The decision support tool appears to be a promising tool in helping to avoid treatments that are unlikely to benefit older women with breast cancer,” Dr. Dossett said. “The results will be widely applicable, as there is growing recognition that this patient population is at risk for overtreatment.”
The study was funded by the U.K. National Institute for Health Research programme grant for applied research. Dr. Wyld and Dr. Dossett said they had no relevant conflicts of interest.
SOURCES: Wyld L et al. EBCC-12 Virtual Congress. Abstract 8A and Abstract 8B.
Findings from the study were reported at the 12th European Breast Cancer Conference.
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.
Cluster-randomized controlled trial
In the cluster-randomized controlled trial, researchers compared a decision support tool to usual care. The tool was developed using U.K. registry data from almost 30,000 older women and input from women in this age group on their preferred format and method of presentation, according to Dr. Wyld.
The tool consists of an algorithm available to clinicians online (for input of tumor stage and biology, comorbidities, and functional status) plus a booklet and outcome sheets for patients to take home after discussions that can be personalized to their particulars.
Intention-to-treat analyses were based on 1,339 patients with operable breast cancer, 1,161 of whom had ER+ disease. Per-protocol analyses were based on the subset of 449 patients who were offered a choice between surgery and primary endocrine therapy, presumably because they were less fit and frailer.
Results showed that, at 6 months, mean scores for global quality of life on the EORTC questionnaire did not differ between decision support and usual care in the intention-to-treat population (69.0 vs. 68.9; P = .900), but scores were more favorable with decision support in the per-protocol population (70.7 vs. 66.8; P = .044).
The tool also altered treatment choices, with a larger share of ER+ patients choosing primary endocrine therapy (21.0% vs. 15.4%; P = .029) but still having similar disease outcomes.
Although ER+ patients in the decision support group more often selected primary endocrine therapy, at a median follow-up of 36 months, the groups did not differ significantly on overall survival, cause-specific survival, or time to recurrence in either intention-to-treat or per-protocol analyses.
Larger shares of women in the decision support group reported that they had adequate knowledge about the treatment options available to them (94% vs. 74%), were aware of the advantages and disadvantages of each option (91% vs. 76%), knew which option they preferred (96% vs. 91%), and were ready to make a decision (99% vs. 90%).
Applying results to practice
“Most women over the age of 70 are relatively fit, and the aim should be to treat them with surgery,” Dr. Wyld said. “For the less fit, a point is reached where the oncology benefits of surgery disappear and surgery may just cause harm. This threshold appears to be for women in their mid-80s with moderate to poor health.”
“Use of the Age Gap online tool may enhance shared decision-making for these women while increasing knowledge. And whilst it does seem to increase the use of primary endocrine therapy, this does not seem to have an adverse impact on survival at 36 months of follow-up,” she added.
“The study by Dr. Wyld and colleagues adds to the available literature regarding the scenarios in which some treatments may be omitted without impacting overall survival in older women with breast cancer,” Lesly A. Dossett, MD, of Michigan Medicine in Ann Arbor, commented in an interview.
In her own practice, Dr. Dossett emphasizes the generally favorable prognosis for older women with hormone receptor–positive breast cancer, she said. However, tools that help communicate risk and clarify the value of various therapies are welcome.
“The decision support tool appears to be a promising tool in helping to avoid treatments that are unlikely to benefit older women with breast cancer,” Dr. Dossett said. “The results will be widely applicable, as there is growing recognition that this patient population is at risk for overtreatment.”
The study was funded by the U.K. National Institute for Health Research programme grant for applied research. Dr. Wyld and Dr. Dossett said they had no relevant conflicts of interest.
SOURCES: Wyld L et al. EBCC-12 Virtual Congress. Abstract 8A and Abstract 8B.
FROM EBCC-12 VIRTUAL CONFERENCE
Breast Cancer Journal Scan: October 2020
Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. A study by Lowry and colleagues evaluated DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. A physician survey showed 30% utilization of DBT, with higher uptake in academic settings and those with higher number of breast imagers and mammography units. Interestingly, 16% of respondents used mammographic density as a criterion to select patients to undergo DBT. Guidelines to help determine which women benefit from DBT would be a useful asset to clinicians and help optimize resources.
Although the majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening. Niraula et al found that interval breast cancers accounted for approximately 20% of cases, were over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. These findings are not entirely surprising as tumors with more aggressive biology are expected to have a faster onset and progression. Development of more personalized screening strategies may help address breast cancer heterogeneity.
Breast cancer diagnosed in women ≥70 years of age tends to be early stage and hormone receptor (HR)-positive. These cancers carry an excellent prognosis, and omission of routine sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (assuming endocrine therapy is given) are acceptable strategies. However, these modalities are still utilized at fairly high rates nationally. Wang and colleagues conducted a qualitative study in women ≥70 years of age without a diagnosis of breast cancer, to evaluate treatment preferences in the setting of a hypothetical diagnosis of low-risk HR-positive breast cancer. A total of 40% stated they would elect to undergo SLNB, regarding the procedure as low-risk and providing prognostic information. Most women (73%) would choose to avoid radiation, due to perception of risk/benefit ratio and inconvenience. This study highlights the importance of effective communication regarding the excellent prognosis of these cancers in older women, and that de-escalation strategies are presented to reduce overtreatment and potential harms while achieving similar benefit.
Higher rates of genetic mutations (non-BRCA 1/2) have been observed in patients with breast cancer and another primary cancer compared to those with single primary breast cancer. Maxwell et al demonstrated rates of 7-9% compared to 4-5% for those with multiple primary breast cancer and single breast cancer, respectively. Further, they showed gene mutations (other than BRCA) are found in up to 25% of patients with breast cancer and another primary with their first breast cancer diagnosed ≤30 years old. Genetic testing is not a one-size fits all method and many patients are offered multigene panel testing. A multidisciplinary approach is key to identifying patients at higher risk, implementing effective screening and hopefully preventing future cancer development.
Erin Roesch, MD
The Cleveland Clinic
References:
Hardesty LA, Kreidler SM, Glueck DH. Digital breast tomosynthesis utilization in the United States: A survey of physician members of the society of breast imaging. J Am Coll Radiol 2016; 11S:R67-R73.
Bellio G, Marion R, Giudici F, Kus S, Tonutti M, Zanconati F, Bortul M. Interval breast cancer versus screen-detected cancer: comparison of clinicopathologic characteristics in a single-center analysis. Clin Breast Cancer. 2017;17:564-71.
Piccinin C, Panchal S, Watkins N, Kim, RH. An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther. 2019; 19:787-801.
Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. A study by Lowry and colleagues evaluated DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. A physician survey showed 30% utilization of DBT, with higher uptake in academic settings and those with higher number of breast imagers and mammography units. Interestingly, 16% of respondents used mammographic density as a criterion to select patients to undergo DBT. Guidelines to help determine which women benefit from DBT would be a useful asset to clinicians and help optimize resources.
Although the majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening. Niraula et al found that interval breast cancers accounted for approximately 20% of cases, were over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. These findings are not entirely surprising as tumors with more aggressive biology are expected to have a faster onset and progression. Development of more personalized screening strategies may help address breast cancer heterogeneity.
Breast cancer diagnosed in women ≥70 years of age tends to be early stage and hormone receptor (HR)-positive. These cancers carry an excellent prognosis, and omission of routine sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (assuming endocrine therapy is given) are acceptable strategies. However, these modalities are still utilized at fairly high rates nationally. Wang and colleagues conducted a qualitative study in women ≥70 years of age without a diagnosis of breast cancer, to evaluate treatment preferences in the setting of a hypothetical diagnosis of low-risk HR-positive breast cancer. A total of 40% stated they would elect to undergo SLNB, regarding the procedure as low-risk and providing prognostic information. Most women (73%) would choose to avoid radiation, due to perception of risk/benefit ratio and inconvenience. This study highlights the importance of effective communication regarding the excellent prognosis of these cancers in older women, and that de-escalation strategies are presented to reduce overtreatment and potential harms while achieving similar benefit.
Higher rates of genetic mutations (non-BRCA 1/2) have been observed in patients with breast cancer and another primary cancer compared to those with single primary breast cancer. Maxwell et al demonstrated rates of 7-9% compared to 4-5% for those with multiple primary breast cancer and single breast cancer, respectively. Further, they showed gene mutations (other than BRCA) are found in up to 25% of patients with breast cancer and another primary with their first breast cancer diagnosed ≤30 years old. Genetic testing is not a one-size fits all method and many patients are offered multigene panel testing. A multidisciplinary approach is key to identifying patients at higher risk, implementing effective screening and hopefully preventing future cancer development.
Erin Roesch, MD
The Cleveland Clinic
References:
Hardesty LA, Kreidler SM, Glueck DH. Digital breast tomosynthesis utilization in the United States: A survey of physician members of the society of breast imaging. J Am Coll Radiol 2016; 11S:R67-R73.
Bellio G, Marion R, Giudici F, Kus S, Tonutti M, Zanconati F, Bortul M. Interval breast cancer versus screen-detected cancer: comparison of clinicopathologic characteristics in a single-center analysis. Clin Breast Cancer. 2017;17:564-71.
Piccinin C, Panchal S, Watkins N, Kim, RH. An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther. 2019; 19:787-801.
Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. A study by Lowry and colleagues evaluated DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. A physician survey showed 30% utilization of DBT, with higher uptake in academic settings and those with higher number of breast imagers and mammography units. Interestingly, 16% of respondents used mammographic density as a criterion to select patients to undergo DBT. Guidelines to help determine which women benefit from DBT would be a useful asset to clinicians and help optimize resources.
Although the majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening. Niraula et al found that interval breast cancers accounted for approximately 20% of cases, were over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. These findings are not entirely surprising as tumors with more aggressive biology are expected to have a faster onset and progression. Development of more personalized screening strategies may help address breast cancer heterogeneity.
Breast cancer diagnosed in women ≥70 years of age tends to be early stage and hormone receptor (HR)-positive. These cancers carry an excellent prognosis, and omission of routine sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy (assuming endocrine therapy is given) are acceptable strategies. However, these modalities are still utilized at fairly high rates nationally. Wang and colleagues conducted a qualitative study in women ≥70 years of age without a diagnosis of breast cancer, to evaluate treatment preferences in the setting of a hypothetical diagnosis of low-risk HR-positive breast cancer. A total of 40% stated they would elect to undergo SLNB, regarding the procedure as low-risk and providing prognostic information. Most women (73%) would choose to avoid radiation, due to perception of risk/benefit ratio and inconvenience. This study highlights the importance of effective communication regarding the excellent prognosis of these cancers in older women, and that de-escalation strategies are presented to reduce overtreatment and potential harms while achieving similar benefit.
Higher rates of genetic mutations (non-BRCA 1/2) have been observed in patients with breast cancer and another primary cancer compared to those with single primary breast cancer. Maxwell et al demonstrated rates of 7-9% compared to 4-5% for those with multiple primary breast cancer and single breast cancer, respectively. Further, they showed gene mutations (other than BRCA) are found in up to 25% of patients with breast cancer and another primary with their first breast cancer diagnosed ≤30 years old. Genetic testing is not a one-size fits all method and many patients are offered multigene panel testing. A multidisciplinary approach is key to identifying patients at higher risk, implementing effective screening and hopefully preventing future cancer development.
Erin Roesch, MD
The Cleveland Clinic
References:
Hardesty LA, Kreidler SM, Glueck DH. Digital breast tomosynthesis utilization in the United States: A survey of physician members of the society of breast imaging. J Am Coll Radiol 2016; 11S:R67-R73.
Bellio G, Marion R, Giudici F, Kus S, Tonutti M, Zanconati F, Bortul M. Interval breast cancer versus screen-detected cancer: comparison of clinicopathologic characteristics in a single-center analysis. Clin Breast Cancer. 2017;17:564-71.
Piccinin C, Panchal S, Watkins N, Kim, RH. An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer. Expert Rev Anticancer Ther. 2019; 19:787-801.
Interval breast cancer has higher hazard for breast cancer death than screen-detected breast cancer
Key clinical point: Interval breast cancers (IBC) were six times more likely to be grade III and had 3.5 times increased hazards of death compared with screen-detected cancers (SBC).
Major finding: Breast cancer–specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio [HR] 3.55; 95% CI, 2.01-6.28; P < .001).
Study details: A cohort study of 69,000 women aged 50-64 years
Disclosures: Dr Hu is the holder of a Manitoba Medical Services Foundation (MMSF) Allen Rouse Basic Science Career Development Research Award.
Source: Niraula, Saroj, MD, MSc, et al. JAMA Netw Open. 2020;3(9):e2018179. doi:10.1001/jamanetworkopen.2020.18179
Key clinical point: Interval breast cancers (IBC) were six times more likely to be grade III and had 3.5 times increased hazards of death compared with screen-detected cancers (SBC).
Major finding: Breast cancer–specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio [HR] 3.55; 95% CI, 2.01-6.28; P < .001).
Study details: A cohort study of 69,000 women aged 50-64 years
Disclosures: Dr Hu is the holder of a Manitoba Medical Services Foundation (MMSF) Allen Rouse Basic Science Career Development Research Award.
Source: Niraula, Saroj, MD, MSc, et al. JAMA Netw Open. 2020;3(9):e2018179. doi:10.1001/jamanetworkopen.2020.18179
Key clinical point: Interval breast cancers (IBC) were six times more likely to be grade III and had 3.5 times increased hazards of death compared with screen-detected cancers (SBC).
Major finding: Breast cancer–specific mortality was significantly higher for IBC compared with SBC cancers (hazard ratio [HR] 3.55; 95% CI, 2.01-6.28; P < .001).
Study details: A cohort study of 69,000 women aged 50-64 years
Disclosures: Dr Hu is the holder of a Manitoba Medical Services Foundation (MMSF) Allen Rouse Basic Science Career Development Research Award.
Source: Niraula, Saroj, MD, MSc, et al. JAMA Netw Open. 2020;3(9):e2018179. doi:10.1001/jamanetworkopen.2020.18179
Ductal carcinoma in situ increases risk of dying from breast cancer by threefold
Key clinical point: Women with ductal carcinoma in situ (DCIS) had a 3-fold increased risk of dying from breast cancer than women without DCIS.
Major finding: Among the cohort, 1,540 women with DCIS died of breast cancer. The expected number of deaths from breast cancer in the cancer-free cohort was 458.
Study details: Cohort study of 144,524 women diagnosed with DCIS from 1995 to 2014.
Disclosures: The authors report no conflicts of interest.
Source: Giannakeas, V, et al. JAMA Netw Open. 2020;3(9):e2017124. doi:10.1001/jamanetworkopen.2020.17124
Key clinical point: Women with ductal carcinoma in situ (DCIS) had a 3-fold increased risk of dying from breast cancer than women without DCIS.
Major finding: Among the cohort, 1,540 women with DCIS died of breast cancer. The expected number of deaths from breast cancer in the cancer-free cohort was 458.
Study details: Cohort study of 144,524 women diagnosed with DCIS from 1995 to 2014.
Disclosures: The authors report no conflicts of interest.
Source: Giannakeas, V, et al. JAMA Netw Open. 2020;3(9):e2017124. doi:10.1001/jamanetworkopen.2020.17124
Key clinical point: Women with ductal carcinoma in situ (DCIS) had a 3-fold increased risk of dying from breast cancer than women without DCIS.
Major finding: Among the cohort, 1,540 women with DCIS died of breast cancer. The expected number of deaths from breast cancer in the cancer-free cohort was 458.
Study details: Cohort study of 144,524 women diagnosed with DCIS from 1995 to 2014.
Disclosures: The authors report no conflicts of interest.
Source: Giannakeas, V, et al. JAMA Netw Open. 2020;3(9):e2017124. doi:10.1001/jamanetworkopen.2020.17124
Women 70 and older are divided on age-based guidelines for breast cancer treatment
Key clinical point: In women aged 70 or older, there are skeptical views on age-based guidelines for breast cancer treatment and difficulty in interpretating the rationale for treatment de-escalation in low-risk, early-stage hormone receptor–positive breast cancer.
Major finding: Approximately 40% of participants stated they would proceed with sentinel lymph node biopsy (SLNB) despite evidence that omission is safe. Conversely, 73% stated they would omit postlumpectomy radiotherapy.
Study details: A qualitative study with 30 female participants, with a median age of 72 years and without a previous diagnosis of breast cancer.
Disclosures: Dr Jagsi reported receiving grants from the National Institutes of Health (NIH), Komen Foundation, Doris Duke Foundation, Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium, and Genentech; grants and personal fees from Greenwall Foundation; personal fees from Amgen, Vizient, Sherinian & Hassostock, and Dressman, Benziger, and Lavelle; and options as compensation for her advisory board role from Equity Quotient; she also reported being an uncompensated founding member of TIME’S UP Healthcare and a member of the American Society of Clinical Oncology Board of Directors. No other disclosures were reported.
Source: Wang, T, et al. JAMA Netw Open. 2020;3(9):e2017129. doi:10.1001/jamanetworkopen.2020.17129
Key clinical point: In women aged 70 or older, there are skeptical views on age-based guidelines for breast cancer treatment and difficulty in interpretating the rationale for treatment de-escalation in low-risk, early-stage hormone receptor–positive breast cancer.
Major finding: Approximately 40% of participants stated they would proceed with sentinel lymph node biopsy (SLNB) despite evidence that omission is safe. Conversely, 73% stated they would omit postlumpectomy radiotherapy.
Study details: A qualitative study with 30 female participants, with a median age of 72 years and without a previous diagnosis of breast cancer.
Disclosures: Dr Jagsi reported receiving grants from the National Institutes of Health (NIH), Komen Foundation, Doris Duke Foundation, Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium, and Genentech; grants and personal fees from Greenwall Foundation; personal fees from Amgen, Vizient, Sherinian & Hassostock, and Dressman, Benziger, and Lavelle; and options as compensation for her advisory board role from Equity Quotient; she also reported being an uncompensated founding member of TIME’S UP Healthcare and a member of the American Society of Clinical Oncology Board of Directors. No other disclosures were reported.
Source: Wang, T, et al. JAMA Netw Open. 2020;3(9):e2017129. doi:10.1001/jamanetworkopen.2020.17129
Key clinical point: In women aged 70 or older, there are skeptical views on age-based guidelines for breast cancer treatment and difficulty in interpretating the rationale for treatment de-escalation in low-risk, early-stage hormone receptor–positive breast cancer.
Major finding: Approximately 40% of participants stated they would proceed with sentinel lymph node biopsy (SLNB) despite evidence that omission is safe. Conversely, 73% stated they would omit postlumpectomy radiotherapy.
Study details: A qualitative study with 30 female participants, with a median age of 72 years and without a previous diagnosis of breast cancer.
Disclosures: Dr Jagsi reported receiving grants from the National Institutes of Health (NIH), Komen Foundation, Doris Duke Foundation, Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium, and Genentech; grants and personal fees from Greenwall Foundation; personal fees from Amgen, Vizient, Sherinian & Hassostock, and Dressman, Benziger, and Lavelle; and options as compensation for her advisory board role from Equity Quotient; she also reported being an uncompensated founding member of TIME’S UP Healthcare and a member of the American Society of Clinical Oncology Board of Directors. No other disclosures were reported.
Source: Wang, T, et al. JAMA Netw Open. 2020;3(9):e2017129. doi:10.1001/jamanetworkopen.2020.17129
Beyond baseline, DBT no better than mammography for dense breasts
Key clinical point: In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the initial exam.
Major finding: For baseline screening in women aged 50-59 years, recall rates per 1,000 exams dropped from 241 with DM to 204 with DBT. Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT. On follow-up exams, recall and cancer detection rates varied by patients’ age and breast density.
Study details: Review of 1,584,079 screenings in women aged 40-79 years.
Disclosures: The research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. The study lead reported grants from GE Healthcare.
Source: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.
Key clinical point: In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the initial exam.
Major finding: For baseline screening in women aged 50-59 years, recall rates per 1,000 exams dropped from 241 with DM to 204 with DBT. Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT. On follow-up exams, recall and cancer detection rates varied by patients’ age and breast density.
Study details: Review of 1,584,079 screenings in women aged 40-79 years.
Disclosures: The research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. The study lead reported grants from GE Healthcare.
Source: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.
Key clinical point: In women with extremely dense breasts, digital breast tomosynthesis (DBT) does not outperform digital mammography (DM) after the initial exam.
Major finding: For baseline screening in women aged 50-59 years, recall rates per 1,000 exams dropped from 241 with DM to 204 with DBT. Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT. On follow-up exams, recall and cancer detection rates varied by patients’ age and breast density.
Study details: Review of 1,584,079 screenings in women aged 40-79 years.
Disclosures: The research was funded by the National Cancer Institute and the Patient-Centered Outcomes Research Institute through the Breast Cancer Surveillance Consortium. The study lead reported grants from GE Healthcare.
Source: Lowry K et al. JAMA Netw Open. 2020 Jul 1;3(7):e2011792.
Study supports multigene panel testing for all breast cancer patients with second primary cancers
Key clinical point: All patients with breast cancer who develop a second primary cancer should undergo multigene panel testing, according to researchers.
Major finding: Mutation rates in BRCA1/2-negative breast cancer patients with multiple primary cancers were approximately 7% to 9%, compared with about 4% to 5% in BRCA1/2-negative patients with a single breast cancer.
Study details: A comparison of mutation rates in 1,000 high-risk breast cancer patients (551 with multiple primary cancers and 449 with a single breast cancer) and 1,804 familial breast cancer patients (340 with multiple primaries and 1,464 with a single breast cancer).
Disclosures: This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Some authors disclosed relationships with a range of companies.
Source: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.
Key clinical point: All patients with breast cancer who develop a second primary cancer should undergo multigene panel testing, according to researchers.
Major finding: Mutation rates in BRCA1/2-negative breast cancer patients with multiple primary cancers were approximately 7% to 9%, compared with about 4% to 5% in BRCA1/2-negative patients with a single breast cancer.
Study details: A comparison of mutation rates in 1,000 high-risk breast cancer patients (551 with multiple primary cancers and 449 with a single breast cancer) and 1,804 familial breast cancer patients (340 with multiple primaries and 1,464 with a single breast cancer).
Disclosures: This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Some authors disclosed relationships with a range of companies.
Source: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.
Key clinical point: All patients with breast cancer who develop a second primary cancer should undergo multigene panel testing, according to researchers.
Major finding: Mutation rates in BRCA1/2-negative breast cancer patients with multiple primary cancers were approximately 7% to 9%, compared with about 4% to 5% in BRCA1/2-negative patients with a single breast cancer.
Study details: A comparison of mutation rates in 1,000 high-risk breast cancer patients (551 with multiple primary cancers and 449 with a single breast cancer) and 1,804 familial breast cancer patients (340 with multiple primaries and 1,464 with a single breast cancer).
Disclosures: This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Some authors disclosed relationships with a range of companies.
Source: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.
AI algorithm on par with radiologists as mammogram reader
Key clinical point: An artificial intelligence computer algorithm performed on par with, and in some cases exceeded, radiologists in reading mammograms from women undergoing routine screening.
Major finding: When operating at a specificity of 96.6%, the sensitivity was 81.9% for the algorithm, 77.4% for first-reader radiologists, and 80.1% for second-reader radiologists.
Study details: A comparison of algorithm and radiologist assessments of mammograms in 8,805 women, 739 of whom were diagnosed with breast cancer.
Disclosures: The research was funded by the Stockholm County Council. The investigators disclosed financial relationships with the Swedish Research Council, the Swedish Cancer Society, Stockholm City Council, Collective Minds Radiology, and Pfizer.
Source: Salim M et al. JAMA Oncol. 2020 Aug 27. doi: 10.1001/jamaoncol.2020.3321.
Key clinical point: An artificial intelligence computer algorithm performed on par with, and in some cases exceeded, radiologists in reading mammograms from women undergoing routine screening.
Major finding: When operating at a specificity of 96.6%, the sensitivity was 81.9% for the algorithm, 77.4% for first-reader radiologists, and 80.1% for second-reader radiologists.
Study details: A comparison of algorithm and radiologist assessments of mammograms in 8,805 women, 739 of whom were diagnosed with breast cancer.
Disclosures: The research was funded by the Stockholm County Council. The investigators disclosed financial relationships with the Swedish Research Council, the Swedish Cancer Society, Stockholm City Council, Collective Minds Radiology, and Pfizer.
Source: Salim M et al. JAMA Oncol. 2020 Aug 27. doi: 10.1001/jamaoncol.2020.3321.
Key clinical point: An artificial intelligence computer algorithm performed on par with, and in some cases exceeded, radiologists in reading mammograms from women undergoing routine screening.
Major finding: When operating at a specificity of 96.6%, the sensitivity was 81.9% for the algorithm, 77.4% for first-reader radiologists, and 80.1% for second-reader radiologists.
Study details: A comparison of algorithm and radiologist assessments of mammograms in 8,805 women, 739 of whom were diagnosed with breast cancer.
Disclosures: The research was funded by the Stockholm County Council. The investigators disclosed financial relationships with the Swedish Research Council, the Swedish Cancer Society, Stockholm City Council, Collective Minds Radiology, and Pfizer.
Source: Salim M et al. JAMA Oncol. 2020 Aug 27. doi: 10.1001/jamaoncol.2020.3321.
How ObGyns can best work with radiologists to optimize screening for patients with dense breasts
If your ObGyn practices are anything like ours, every time there is news coverage of a study regarding mammography or about efforts to pass a breast density inform law, your phone rings with patient calls. In fact, every density inform law enacted in the United States, except for in Illinois, directs patients to their referring provider—generally their ObGyn—to discuss the screening and risk implications of dense breast tissue.
The steady increased awareness of breast density means that we, as ObGyns and other primary care providers (PCPs), have additional responsibilities in managing the breast health of our patients. This includes guiding discussions with patients about what breast density means and whether supplemental screening beyond mammography might be beneficial.
As members of the Medical Advisory Board for DenseBreast-info.org (an online educational resource dedicated to providing breast density information to patients and health care professionals), we are aware of the growing body of evidence demonstrating improved detection of early breast cancer using supplemental screening in dense breasts. However, we know that there is confusion among clinicians about how and when to facilitate tailored screening for women with dense breasts or other breast cancer risk factors. Here we answer 6 questions focusing on how to navigate patient discussions around the topic and the best way to collaborate with radiologists to improve breast care for patients.
Play an active role
1. What role should ObGyns and PCPs play in women’s breast health?
Elizabeth Etkin-Kramer, MD: I am a firm believer that ObGyns and all women’s health providers should be able to assess their patients’ risk of breast cancer and explain the process for managing this risk with their patients. This explanation includes the clinical implications of breast density and when supplemental screening should be employed. It is also important for providers to know when to offer genetic testing and when a patient’s personal or family history indicates supplemental screening with breast magnetic resonance imaging (MRI).
DaCarla M. Albright, MD: I absolutely agree that PCPs, ObGyns, and family practitioners should spend the time to be educated about breast density and supplemental screening options. While the exact role providers play in managing patients’ breast health may vary depending on the practice type or location, the need for knowledge and comfort when talking with patients to help them make informed decisions is critical. Breast health and screening, including the importance of breast density, happen to be a particular interest of mine. I have participated in educational webinars, invited lectures, and breast cancer awareness media events on this topic in the past.
Continue to: Join forces with imaging centers...
Join forces with imaging centers
2. How can ObGyns and radiologists collaborate most effectively to use screening results to personalize breast care for patients?
Dr. Etkin-Kramer: It is important to have a close relationship with the radiologists that read our patients’ mammograms. We need to be able to easily contact the radiologist and quickly get clarification on a patient’s report or discuss next steps. Imaging centers should consider running outreach programs to educate their referring providers on how to risk assess, with this assessment inclusive of breast density. Dinner lectures or grand round meetings are effective to facilitate communication between the radiology community and the ObGyn community. Finally, as we all know, supplemental screening is often subject to copays and deductibles per insurance coverage. If advocacy groups, who are working to eliminate these types of costs, cannot get insurers to waive these payments, we need a less expensive self-pay option.
Dr. Albright: I definitely have and encourage an open line of communication between my practice and breast radiology, as well as our breast surgeons and cancer center to set up consultations as needed. We also invite our radiologists as guests to monthly practice meetings or grand rounds within our department to further improve access and open communication, as this environment is one in which greater provider education on density and adjunctive screening can be achieved.
Know when to refer a high-risk patient
3. Most ObGyns routinely collect family history and perform formal risk assessment. What do you need to know about referring patients to a high-risk program?
Dr. Etkin-Kramer: It is important as ObGyns to be knowledgeable about breast and ovarian cancer risk assessment and genetic testing for cancer susceptibility genes. Our patients expect that of us. I am comfortable doing risk assessment in my office, but I sometimes refer to other specialists in the community if the patient needs additional counseling. For risk assessment, I look at family and personal history, breast density, and other factors that might lead me to believe the patient might carry a hereditary cancer susceptibility gene, including Ashkenazi Jewish ancestry.1 When indicated, I check lifetime as well as short-term (5- to 10-year) risk, usually using Breast Cancer Surveillance Consortium (BCSC) or Tyrer-Cuzick/International Breast Cancer Intervention Study (IBIS) models, as these include breast density.
I discuss risk-reducing medications. The US Preventive Services Task Force recommends these agents if my patient’s 5-year risk of breast cancer is 1.67% or greater, and I strongly recommend chemoprevention when the patient’s 5-year BCSC risk exceeds 3%, provided likely benefits exceed risks.2,3 I discuss adding screening breast MRI if lifetime risk by Tyrer-Cuzick exceeds 20%. (Note that Gail and BCSC models are not recommended to be used to determine risk for purposes of supplemental screening with MRI as they do not consider paternal family history nor age of relatives at diagnosis.)
Dr. Albright: ObGyns should be able to ascertain a pertinent history and identify patients at risk for breast cancer based on their personal history, family history, and breast imaging/biopsy history, if relevant. We also need to improve our discussions of supplemental screening for patients who have heterogeneously dense or extremely dense breast tissue. I sense that some ObGyns may rely heavily on the radiologist to suggest supplemental screening, but patients actually look to ObGyns as their providers to have this knowledge and give them direction.
Since I practice at a large academic medical center, I have the opportunity to refer patients to our Breast Cancer Genetics Program because I may be limited on time for counseling in the office and do not want to miss salient details. With all of the information I have ascertained about the patient, I am able to determine and encourage appropriate screening and assure insurance coverage for adjunctive breast MRI when appropriate.
Continue to: Consider how you order patients’ screening to reduce barriers and cost...
Consider how you order patients’ screening to reduce barriers and cost
4. How would you suggest reducing barriers when referring patients for supplemental screening, such as MRI for high-risk women or ultrasound for those with dense breasts? Would you prefer it if such screening could be performed without additional script/referral? How does insurance coverage factor in?
Dr. Etkin-Kramer: I would love for a screening mammogram with possible ultrasound, on one script, to be the norm. One of the centers that I work with accepts a script written this way. Further, when a patient receives screening at a freestanding facility as opposed to a hospital, the fee for the supplemental screening may be lower because they do not add on a facility fee.
Dr. Albright: We have an order in our electronic health record that allows for screening mammography but adds on diagnostic mammography/bilateral ultrasonography, if indicated by imaging. I am mostly ordering that option now for all of my screening patients; rarely have I had issues with insurance accepting that script. As for when ordering an MRI, I always try to ensure that I have done the patient’s personal risk assessment and included that lifetime breast cancer risk on the order. If the risk is 20% or higher, I typically do not have any insurance coverage issues. If I am ordering MRI as supplemental screening, I typically order the “Fast MRI” protocol that our center offers. This order incurs a $299 out-of-pocket cost for the patient. Any patient with heterogeneously or extremely dense breasts on mammography should have this option, but it requires patient education, discussion with the provider, and an additional cost. I definitely think that insurers need to consider covering supplemental screening, since breast density is reportable in a majority of the US states and will soon be the national standard.
Pearls for guiding patients
5. How do you discuss breast density and the need for supplemental screening with your patients?
Dr. Etkin-Kramer: I strongly feel that my patients need to know when a screening test has limited ability to do its job. This is the case with dense breasts. Visuals help; when discussing breast density, I like the images supplied by DenseBreast-info.org (FIGURE). I explain the two implications of dense tissue:
- First, dense tissue makes it harder to visualize cancers in the breast—the denser the breasts, the less likely the radiologist can pick up a cancer, so mammographic sensitivity for extremely dense breasts can be as low as 25% to 50%.
- Second, high breast density adds to the risk of developing breast cancer. I explain that supplemental screening will pick up additional cancers in women with dense breasts. For example, breast ultrasound will pick up about 2-3/1000 additional breast cancers per year and MRI or molecular breast imaging (MBI) will pick up much more, perhaps 10/1000.
MRI is more invasive than an ultrasound and uses gadolinium, and MBI has more radiation. Supplemental screening is not endorsed by ACOG’s most recent Committee Opinion from 2017; 4 however, patients may choose to have it done. This is where shared-decision making is important.
I strongly recommend that all women’s health care providers complete the CME course on the DenseBreast-info.org website. “ Breast Density: Why It Matters ” is a certified educational program for referring physicians that helps health care professionals learn about breast density, its associated risks, and how best to guide patients regarding breast cancer screening.
Continue to: Dr. Albright...
Dr. Albright: When I discuss breast density, I make sure that patients understand that their mammogram determines the density of their breast tissue. I review that in the higher density categories (heterogeneously dense or extremely dense), there is a higher risk of missing cancer, and that these categories are also associated with a higher risk of breast cancer. I also discuss the potential need for supplemental screening, for which my institution primarily offers Fast MRI. However, we can offer breast ultrasonography instead as an option, especially for those concerned about gadolinium exposure. Our center offers either of these supplemental screenings at a cost of $299. I also review the lack of coverage for supplemental screening by some insurance carriers, as both providers and patients may need to advocate for insurer coverage of adjunct studies.
Educational resources
6. What reference materials, illustrations, or other tools do you use to educate your patients?
Dr. Etkin-Kramer: I frequently use handouts printed from the DenseBreast-info.org website, and there is now a brand new patient fact sheet that I have just started using. I also have an example of breast density categories from fatty replaced to extremely dense on my computer, and I am putting it on a new smart board.
Dr. Albright: The extensive resources available at DenseBreast-info.org can improve both patient and provider knowledge of these important issues, so I suggest patients visit that website, and I use many of the images and visuals to help explain breast density. I even use the materials from the website for educating my resident trainees on breast health and screening. ●
Nearly 16,000 children (up to age 19 years) face cancer-related treatment every year.1 For girls and young women, undergoing chest radiotherapy puts them at higher risk for secondary breast cancer. In fact, they have a 30% chance of developing such cancer by age 50—a risk that is similar to women with a BRCA1 mutation.2 Therefore, current recommendations for breast cancer screening among those who have undergone childhood chest radiation (≥20 Gy) are to begin annual mammography, with adjunct magnetic resonance imaging (MRI), at age 25 years (or 8 years after chest radiotherapy).3
To determine the benefits and risks of these recommendations, as well as of similar strategies, Yeh and colleagues performed simulation modeling using data from the Childhood Cancer Survivor Study and two CISNET (Cancer Intervention and Surveillance Modeling Network) models.4 For their study they targeted a cohort of female childhood cancer survivors having undergone chest radiotherapy and evaluated breast cancer screening with the following strategies:
- mammography plus MRI, starting at ages 25, 30, or 35 years and continuing to age 74
- MRI alone, starting at ages 25, 30, or 35 years and continuing to age 74.
They found that both strategies reduced the risk of breast cancer in the targeted cohort but that screening beginning at the earliest ages prevented most deaths. No screening at all was associated with a 10% to 11% lifetime risk of breast cancer, but mammography plus MRI beginning at age 25 reduced that risk by 56% to 71% depending on the model. Screening with MRI alone reduced mortality risk by 56% to 62%. When considering cost per quality adjusted life-year gained, the researchers found that screening beginning at age 30 to be the most cost-effective.4
Yeh and colleagues addressed concerns with mammography and radiation. Although they said the associated amount of radiation exposure is small, the use of mammography in women younger than age 30 is controversial—and not recommended by the American Cancer Society or the National Comprehensive Cancer Network.5,6
Bottom line. Yeh and colleagues conclude that MRI screening, with or without mammography, beginning between the ages of 25 and 30 should be emphasized in screening guidelines. They note the importance of insurance coverage for MRI in those at risk for breast cancer due to childhood radiation exposure.4
References
- National Cancer Institute. How common is cancer in children? https://www.cancer.gov/types/childhood-cancers/child-adolescentcancers-fact-sheet#how-common-is-cancer-in-children. Accessed September 25, 2020.
- Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217- 2223.
- Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http:// www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Accessed September 25, 2020.
- Yeh JM, Lowry KP, Schechter CB, et al. Clinical benefits, harms, and cost-effectiveness of breast cancer screening for survivors of childhood cancer treated with chest radiation. Ann Intern Med. 2020;173:331-341.
- Saslow D, Boetes C, Burke W, et al; American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast cancer screening and diagnosis version 1.2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed September 25, 2020.
- Bharucha PP, Chiu KE, Francois FM, et al. Genetic testing and screening recommendations for patients with hereditary breast cancer. RadioGraphics. 2020;40:913-936.
- Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29:2327-2333.
- Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230-3235.
- American College of Obstetricians and Gynecologists. Committee opinion no. 625: management of women with dense breasts diagnosed by mammography [published correction appears in Obstet Gynecol. 2016;127:166]. Obstet Gynecol. 2015;125(3):750-751.
If your ObGyn practices are anything like ours, every time there is news coverage of a study regarding mammography or about efforts to pass a breast density inform law, your phone rings with patient calls. In fact, every density inform law enacted in the United States, except for in Illinois, directs patients to their referring provider—generally their ObGyn—to discuss the screening and risk implications of dense breast tissue.
The steady increased awareness of breast density means that we, as ObGyns and other primary care providers (PCPs), have additional responsibilities in managing the breast health of our patients. This includes guiding discussions with patients about what breast density means and whether supplemental screening beyond mammography might be beneficial.
As members of the Medical Advisory Board for DenseBreast-info.org (an online educational resource dedicated to providing breast density information to patients and health care professionals), we are aware of the growing body of evidence demonstrating improved detection of early breast cancer using supplemental screening in dense breasts. However, we know that there is confusion among clinicians about how and when to facilitate tailored screening for women with dense breasts or other breast cancer risk factors. Here we answer 6 questions focusing on how to navigate patient discussions around the topic and the best way to collaborate with radiologists to improve breast care for patients.
Play an active role
1. What role should ObGyns and PCPs play in women’s breast health?
Elizabeth Etkin-Kramer, MD: I am a firm believer that ObGyns and all women’s health providers should be able to assess their patients’ risk of breast cancer and explain the process for managing this risk with their patients. This explanation includes the clinical implications of breast density and when supplemental screening should be employed. It is also important for providers to know when to offer genetic testing and when a patient’s personal or family history indicates supplemental screening with breast magnetic resonance imaging (MRI).
DaCarla M. Albright, MD: I absolutely agree that PCPs, ObGyns, and family practitioners should spend the time to be educated about breast density and supplemental screening options. While the exact role providers play in managing patients’ breast health may vary depending on the practice type or location, the need for knowledge and comfort when talking with patients to help them make informed decisions is critical. Breast health and screening, including the importance of breast density, happen to be a particular interest of mine. I have participated in educational webinars, invited lectures, and breast cancer awareness media events on this topic in the past.
Continue to: Join forces with imaging centers...
Join forces with imaging centers
2. How can ObGyns and radiologists collaborate most effectively to use screening results to personalize breast care for patients?
Dr. Etkin-Kramer: It is important to have a close relationship with the radiologists that read our patients’ mammograms. We need to be able to easily contact the radiologist and quickly get clarification on a patient’s report or discuss next steps. Imaging centers should consider running outreach programs to educate their referring providers on how to risk assess, with this assessment inclusive of breast density. Dinner lectures or grand round meetings are effective to facilitate communication between the radiology community and the ObGyn community. Finally, as we all know, supplemental screening is often subject to copays and deductibles per insurance coverage. If advocacy groups, who are working to eliminate these types of costs, cannot get insurers to waive these payments, we need a less expensive self-pay option.
Dr. Albright: I definitely have and encourage an open line of communication between my practice and breast radiology, as well as our breast surgeons and cancer center to set up consultations as needed. We also invite our radiologists as guests to monthly practice meetings or grand rounds within our department to further improve access and open communication, as this environment is one in which greater provider education on density and adjunctive screening can be achieved.
Know when to refer a high-risk patient
3. Most ObGyns routinely collect family history and perform formal risk assessment. What do you need to know about referring patients to a high-risk program?
Dr. Etkin-Kramer: It is important as ObGyns to be knowledgeable about breast and ovarian cancer risk assessment and genetic testing for cancer susceptibility genes. Our patients expect that of us. I am comfortable doing risk assessment in my office, but I sometimes refer to other specialists in the community if the patient needs additional counseling. For risk assessment, I look at family and personal history, breast density, and other factors that might lead me to believe the patient might carry a hereditary cancer susceptibility gene, including Ashkenazi Jewish ancestry.1 When indicated, I check lifetime as well as short-term (5- to 10-year) risk, usually using Breast Cancer Surveillance Consortium (BCSC) or Tyrer-Cuzick/International Breast Cancer Intervention Study (IBIS) models, as these include breast density.
I discuss risk-reducing medications. The US Preventive Services Task Force recommends these agents if my patient’s 5-year risk of breast cancer is 1.67% or greater, and I strongly recommend chemoprevention when the patient’s 5-year BCSC risk exceeds 3%, provided likely benefits exceed risks.2,3 I discuss adding screening breast MRI if lifetime risk by Tyrer-Cuzick exceeds 20%. (Note that Gail and BCSC models are not recommended to be used to determine risk for purposes of supplemental screening with MRI as they do not consider paternal family history nor age of relatives at diagnosis.)
Dr. Albright: ObGyns should be able to ascertain a pertinent history and identify patients at risk for breast cancer based on their personal history, family history, and breast imaging/biopsy history, if relevant. We also need to improve our discussions of supplemental screening for patients who have heterogeneously dense or extremely dense breast tissue. I sense that some ObGyns may rely heavily on the radiologist to suggest supplemental screening, but patients actually look to ObGyns as their providers to have this knowledge and give them direction.
Since I practice at a large academic medical center, I have the opportunity to refer patients to our Breast Cancer Genetics Program because I may be limited on time for counseling in the office and do not want to miss salient details. With all of the information I have ascertained about the patient, I am able to determine and encourage appropriate screening and assure insurance coverage for adjunctive breast MRI when appropriate.
Continue to: Consider how you order patients’ screening to reduce barriers and cost...
Consider how you order patients’ screening to reduce barriers and cost
4. How would you suggest reducing barriers when referring patients for supplemental screening, such as MRI for high-risk women or ultrasound for those with dense breasts? Would you prefer it if such screening could be performed without additional script/referral? How does insurance coverage factor in?
Dr. Etkin-Kramer: I would love for a screening mammogram with possible ultrasound, on one script, to be the norm. One of the centers that I work with accepts a script written this way. Further, when a patient receives screening at a freestanding facility as opposed to a hospital, the fee for the supplemental screening may be lower because they do not add on a facility fee.
Dr. Albright: We have an order in our electronic health record that allows for screening mammography but adds on diagnostic mammography/bilateral ultrasonography, if indicated by imaging. I am mostly ordering that option now for all of my screening patients; rarely have I had issues with insurance accepting that script. As for when ordering an MRI, I always try to ensure that I have done the patient’s personal risk assessment and included that lifetime breast cancer risk on the order. If the risk is 20% or higher, I typically do not have any insurance coverage issues. If I am ordering MRI as supplemental screening, I typically order the “Fast MRI” protocol that our center offers. This order incurs a $299 out-of-pocket cost for the patient. Any patient with heterogeneously or extremely dense breasts on mammography should have this option, but it requires patient education, discussion with the provider, and an additional cost. I definitely think that insurers need to consider covering supplemental screening, since breast density is reportable in a majority of the US states and will soon be the national standard.
Pearls for guiding patients
5. How do you discuss breast density and the need for supplemental screening with your patients?
Dr. Etkin-Kramer: I strongly feel that my patients need to know when a screening test has limited ability to do its job. This is the case with dense breasts. Visuals help; when discussing breast density, I like the images supplied by DenseBreast-info.org (FIGURE). I explain the two implications of dense tissue:
- First, dense tissue makes it harder to visualize cancers in the breast—the denser the breasts, the less likely the radiologist can pick up a cancer, so mammographic sensitivity for extremely dense breasts can be as low as 25% to 50%.
- Second, high breast density adds to the risk of developing breast cancer. I explain that supplemental screening will pick up additional cancers in women with dense breasts. For example, breast ultrasound will pick up about 2-3/1000 additional breast cancers per year and MRI or molecular breast imaging (MBI) will pick up much more, perhaps 10/1000.
MRI is more invasive than an ultrasound and uses gadolinium, and MBI has more radiation. Supplemental screening is not endorsed by ACOG’s most recent Committee Opinion from 2017; 4 however, patients may choose to have it done. This is where shared-decision making is important.
I strongly recommend that all women’s health care providers complete the CME course on the DenseBreast-info.org website. “ Breast Density: Why It Matters ” is a certified educational program for referring physicians that helps health care professionals learn about breast density, its associated risks, and how best to guide patients regarding breast cancer screening.
Continue to: Dr. Albright...
Dr. Albright: When I discuss breast density, I make sure that patients understand that their mammogram determines the density of their breast tissue. I review that in the higher density categories (heterogeneously dense or extremely dense), there is a higher risk of missing cancer, and that these categories are also associated with a higher risk of breast cancer. I also discuss the potential need for supplemental screening, for which my institution primarily offers Fast MRI. However, we can offer breast ultrasonography instead as an option, especially for those concerned about gadolinium exposure. Our center offers either of these supplemental screenings at a cost of $299. I also review the lack of coverage for supplemental screening by some insurance carriers, as both providers and patients may need to advocate for insurer coverage of adjunct studies.
Educational resources
6. What reference materials, illustrations, or other tools do you use to educate your patients?
Dr. Etkin-Kramer: I frequently use handouts printed from the DenseBreast-info.org website, and there is now a brand new patient fact sheet that I have just started using. I also have an example of breast density categories from fatty replaced to extremely dense on my computer, and I am putting it on a new smart board.
Dr. Albright: The extensive resources available at DenseBreast-info.org can improve both patient and provider knowledge of these important issues, so I suggest patients visit that website, and I use many of the images and visuals to help explain breast density. I even use the materials from the website for educating my resident trainees on breast health and screening. ●
Nearly 16,000 children (up to age 19 years) face cancer-related treatment every year.1 For girls and young women, undergoing chest radiotherapy puts them at higher risk for secondary breast cancer. In fact, they have a 30% chance of developing such cancer by age 50—a risk that is similar to women with a BRCA1 mutation.2 Therefore, current recommendations for breast cancer screening among those who have undergone childhood chest radiation (≥20 Gy) are to begin annual mammography, with adjunct magnetic resonance imaging (MRI), at age 25 years (or 8 years after chest radiotherapy).3
To determine the benefits and risks of these recommendations, as well as of similar strategies, Yeh and colleagues performed simulation modeling using data from the Childhood Cancer Survivor Study and two CISNET (Cancer Intervention and Surveillance Modeling Network) models.4 For their study they targeted a cohort of female childhood cancer survivors having undergone chest radiotherapy and evaluated breast cancer screening with the following strategies:
- mammography plus MRI, starting at ages 25, 30, or 35 years and continuing to age 74
- MRI alone, starting at ages 25, 30, or 35 years and continuing to age 74.
They found that both strategies reduced the risk of breast cancer in the targeted cohort but that screening beginning at the earliest ages prevented most deaths. No screening at all was associated with a 10% to 11% lifetime risk of breast cancer, but mammography plus MRI beginning at age 25 reduced that risk by 56% to 71% depending on the model. Screening with MRI alone reduced mortality risk by 56% to 62%. When considering cost per quality adjusted life-year gained, the researchers found that screening beginning at age 30 to be the most cost-effective.4
Yeh and colleagues addressed concerns with mammography and radiation. Although they said the associated amount of radiation exposure is small, the use of mammography in women younger than age 30 is controversial—and not recommended by the American Cancer Society or the National Comprehensive Cancer Network.5,6
Bottom line. Yeh and colleagues conclude that MRI screening, with or without mammography, beginning between the ages of 25 and 30 should be emphasized in screening guidelines. They note the importance of insurance coverage for MRI in those at risk for breast cancer due to childhood radiation exposure.4
References
- National Cancer Institute. How common is cancer in children? https://www.cancer.gov/types/childhood-cancers/child-adolescentcancers-fact-sheet#how-common-is-cancer-in-children. Accessed September 25, 2020.
- Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217- 2223.
- Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http:// www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Accessed September 25, 2020.
- Yeh JM, Lowry KP, Schechter CB, et al. Clinical benefits, harms, and cost-effectiveness of breast cancer screening for survivors of childhood cancer treated with chest radiation. Ann Intern Med. 2020;173:331-341.
- Saslow D, Boetes C, Burke W, et al; American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast cancer screening and diagnosis version 1.2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed September 25, 2020.
If your ObGyn practices are anything like ours, every time there is news coverage of a study regarding mammography or about efforts to pass a breast density inform law, your phone rings with patient calls. In fact, every density inform law enacted in the United States, except for in Illinois, directs patients to their referring provider—generally their ObGyn—to discuss the screening and risk implications of dense breast tissue.
The steady increased awareness of breast density means that we, as ObGyns and other primary care providers (PCPs), have additional responsibilities in managing the breast health of our patients. This includes guiding discussions with patients about what breast density means and whether supplemental screening beyond mammography might be beneficial.
As members of the Medical Advisory Board for DenseBreast-info.org (an online educational resource dedicated to providing breast density information to patients and health care professionals), we are aware of the growing body of evidence demonstrating improved detection of early breast cancer using supplemental screening in dense breasts. However, we know that there is confusion among clinicians about how and when to facilitate tailored screening for women with dense breasts or other breast cancer risk factors. Here we answer 6 questions focusing on how to navigate patient discussions around the topic and the best way to collaborate with radiologists to improve breast care for patients.
Play an active role
1. What role should ObGyns and PCPs play in women’s breast health?
Elizabeth Etkin-Kramer, MD: I am a firm believer that ObGyns and all women’s health providers should be able to assess their patients’ risk of breast cancer and explain the process for managing this risk with their patients. This explanation includes the clinical implications of breast density and when supplemental screening should be employed. It is also important for providers to know when to offer genetic testing and when a patient’s personal or family history indicates supplemental screening with breast magnetic resonance imaging (MRI).
DaCarla M. Albright, MD: I absolutely agree that PCPs, ObGyns, and family practitioners should spend the time to be educated about breast density and supplemental screening options. While the exact role providers play in managing patients’ breast health may vary depending on the practice type or location, the need for knowledge and comfort when talking with patients to help them make informed decisions is critical. Breast health and screening, including the importance of breast density, happen to be a particular interest of mine. I have participated in educational webinars, invited lectures, and breast cancer awareness media events on this topic in the past.
Continue to: Join forces with imaging centers...
Join forces with imaging centers
2. How can ObGyns and radiologists collaborate most effectively to use screening results to personalize breast care for patients?
Dr. Etkin-Kramer: It is important to have a close relationship with the radiologists that read our patients’ mammograms. We need to be able to easily contact the radiologist and quickly get clarification on a patient’s report or discuss next steps. Imaging centers should consider running outreach programs to educate their referring providers on how to risk assess, with this assessment inclusive of breast density. Dinner lectures or grand round meetings are effective to facilitate communication between the radiology community and the ObGyn community. Finally, as we all know, supplemental screening is often subject to copays and deductibles per insurance coverage. If advocacy groups, who are working to eliminate these types of costs, cannot get insurers to waive these payments, we need a less expensive self-pay option.
Dr. Albright: I definitely have and encourage an open line of communication between my practice and breast radiology, as well as our breast surgeons and cancer center to set up consultations as needed. We also invite our radiologists as guests to monthly practice meetings or grand rounds within our department to further improve access and open communication, as this environment is one in which greater provider education on density and adjunctive screening can be achieved.
Know when to refer a high-risk patient
3. Most ObGyns routinely collect family history and perform formal risk assessment. What do you need to know about referring patients to a high-risk program?
Dr. Etkin-Kramer: It is important as ObGyns to be knowledgeable about breast and ovarian cancer risk assessment and genetic testing for cancer susceptibility genes. Our patients expect that of us. I am comfortable doing risk assessment in my office, but I sometimes refer to other specialists in the community if the patient needs additional counseling. For risk assessment, I look at family and personal history, breast density, and other factors that might lead me to believe the patient might carry a hereditary cancer susceptibility gene, including Ashkenazi Jewish ancestry.1 When indicated, I check lifetime as well as short-term (5- to 10-year) risk, usually using Breast Cancer Surveillance Consortium (BCSC) or Tyrer-Cuzick/International Breast Cancer Intervention Study (IBIS) models, as these include breast density.
I discuss risk-reducing medications. The US Preventive Services Task Force recommends these agents if my patient’s 5-year risk of breast cancer is 1.67% or greater, and I strongly recommend chemoprevention when the patient’s 5-year BCSC risk exceeds 3%, provided likely benefits exceed risks.2,3 I discuss adding screening breast MRI if lifetime risk by Tyrer-Cuzick exceeds 20%. (Note that Gail and BCSC models are not recommended to be used to determine risk for purposes of supplemental screening with MRI as they do not consider paternal family history nor age of relatives at diagnosis.)
Dr. Albright: ObGyns should be able to ascertain a pertinent history and identify patients at risk for breast cancer based on their personal history, family history, and breast imaging/biopsy history, if relevant. We also need to improve our discussions of supplemental screening for patients who have heterogeneously dense or extremely dense breast tissue. I sense that some ObGyns may rely heavily on the radiologist to suggest supplemental screening, but patients actually look to ObGyns as their providers to have this knowledge and give them direction.
Since I practice at a large academic medical center, I have the opportunity to refer patients to our Breast Cancer Genetics Program because I may be limited on time for counseling in the office and do not want to miss salient details. With all of the information I have ascertained about the patient, I am able to determine and encourage appropriate screening and assure insurance coverage for adjunctive breast MRI when appropriate.
Continue to: Consider how you order patients’ screening to reduce barriers and cost...
Consider how you order patients’ screening to reduce barriers and cost
4. How would you suggest reducing barriers when referring patients for supplemental screening, such as MRI for high-risk women or ultrasound for those with dense breasts? Would you prefer it if such screening could be performed without additional script/referral? How does insurance coverage factor in?
Dr. Etkin-Kramer: I would love for a screening mammogram with possible ultrasound, on one script, to be the norm. One of the centers that I work with accepts a script written this way. Further, when a patient receives screening at a freestanding facility as opposed to a hospital, the fee for the supplemental screening may be lower because they do not add on a facility fee.
Dr. Albright: We have an order in our electronic health record that allows for screening mammography but adds on diagnostic mammography/bilateral ultrasonography, if indicated by imaging. I am mostly ordering that option now for all of my screening patients; rarely have I had issues with insurance accepting that script. As for when ordering an MRI, I always try to ensure that I have done the patient’s personal risk assessment and included that lifetime breast cancer risk on the order. If the risk is 20% or higher, I typically do not have any insurance coverage issues. If I am ordering MRI as supplemental screening, I typically order the “Fast MRI” protocol that our center offers. This order incurs a $299 out-of-pocket cost for the patient. Any patient with heterogeneously or extremely dense breasts on mammography should have this option, but it requires patient education, discussion with the provider, and an additional cost. I definitely think that insurers need to consider covering supplemental screening, since breast density is reportable in a majority of the US states and will soon be the national standard.
Pearls for guiding patients
5. How do you discuss breast density and the need for supplemental screening with your patients?
Dr. Etkin-Kramer: I strongly feel that my patients need to know when a screening test has limited ability to do its job. This is the case with dense breasts. Visuals help; when discussing breast density, I like the images supplied by DenseBreast-info.org (FIGURE). I explain the two implications of dense tissue:
- First, dense tissue makes it harder to visualize cancers in the breast—the denser the breasts, the less likely the radiologist can pick up a cancer, so mammographic sensitivity for extremely dense breasts can be as low as 25% to 50%.
- Second, high breast density adds to the risk of developing breast cancer. I explain that supplemental screening will pick up additional cancers in women with dense breasts. For example, breast ultrasound will pick up about 2-3/1000 additional breast cancers per year and MRI or molecular breast imaging (MBI) will pick up much more, perhaps 10/1000.
MRI is more invasive than an ultrasound and uses gadolinium, and MBI has more radiation. Supplemental screening is not endorsed by ACOG’s most recent Committee Opinion from 2017; 4 however, patients may choose to have it done. This is where shared-decision making is important.
I strongly recommend that all women’s health care providers complete the CME course on the DenseBreast-info.org website. “ Breast Density: Why It Matters ” is a certified educational program for referring physicians that helps health care professionals learn about breast density, its associated risks, and how best to guide patients regarding breast cancer screening.
Continue to: Dr. Albright...
Dr. Albright: When I discuss breast density, I make sure that patients understand that their mammogram determines the density of their breast tissue. I review that in the higher density categories (heterogeneously dense or extremely dense), there is a higher risk of missing cancer, and that these categories are also associated with a higher risk of breast cancer. I also discuss the potential need for supplemental screening, for which my institution primarily offers Fast MRI. However, we can offer breast ultrasonography instead as an option, especially for those concerned about gadolinium exposure. Our center offers either of these supplemental screenings at a cost of $299. I also review the lack of coverage for supplemental screening by some insurance carriers, as both providers and patients may need to advocate for insurer coverage of adjunct studies.
Educational resources
6. What reference materials, illustrations, or other tools do you use to educate your patients?
Dr. Etkin-Kramer: I frequently use handouts printed from the DenseBreast-info.org website, and there is now a brand new patient fact sheet that I have just started using. I also have an example of breast density categories from fatty replaced to extremely dense on my computer, and I am putting it on a new smart board.
Dr. Albright: The extensive resources available at DenseBreast-info.org can improve both patient and provider knowledge of these important issues, so I suggest patients visit that website, and I use many of the images and visuals to help explain breast density. I even use the materials from the website for educating my resident trainees on breast health and screening. ●
Nearly 16,000 children (up to age 19 years) face cancer-related treatment every year.1 For girls and young women, undergoing chest radiotherapy puts them at higher risk for secondary breast cancer. In fact, they have a 30% chance of developing such cancer by age 50—a risk that is similar to women with a BRCA1 mutation.2 Therefore, current recommendations for breast cancer screening among those who have undergone childhood chest radiation (≥20 Gy) are to begin annual mammography, with adjunct magnetic resonance imaging (MRI), at age 25 years (or 8 years after chest radiotherapy).3
To determine the benefits and risks of these recommendations, as well as of similar strategies, Yeh and colleagues performed simulation modeling using data from the Childhood Cancer Survivor Study and two CISNET (Cancer Intervention and Surveillance Modeling Network) models.4 For their study they targeted a cohort of female childhood cancer survivors having undergone chest radiotherapy and evaluated breast cancer screening with the following strategies:
- mammography plus MRI, starting at ages 25, 30, or 35 years and continuing to age 74
- MRI alone, starting at ages 25, 30, or 35 years and continuing to age 74.
They found that both strategies reduced the risk of breast cancer in the targeted cohort but that screening beginning at the earliest ages prevented most deaths. No screening at all was associated with a 10% to 11% lifetime risk of breast cancer, but mammography plus MRI beginning at age 25 reduced that risk by 56% to 71% depending on the model. Screening with MRI alone reduced mortality risk by 56% to 62%. When considering cost per quality adjusted life-year gained, the researchers found that screening beginning at age 30 to be the most cost-effective.4
Yeh and colleagues addressed concerns with mammography and radiation. Although they said the associated amount of radiation exposure is small, the use of mammography in women younger than age 30 is controversial—and not recommended by the American Cancer Society or the National Comprehensive Cancer Network.5,6
Bottom line. Yeh and colleagues conclude that MRI screening, with or without mammography, beginning between the ages of 25 and 30 should be emphasized in screening guidelines. They note the importance of insurance coverage for MRI in those at risk for breast cancer due to childhood radiation exposure.4
References
- National Cancer Institute. How common is cancer in children? https://www.cancer.gov/types/childhood-cancers/child-adolescentcancers-fact-sheet#how-common-is-cancer-in-children. Accessed September 25, 2020.
- Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217- 2223.
- Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http:// www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Accessed September 25, 2020.
- Yeh JM, Lowry KP, Schechter CB, et al. Clinical benefits, harms, and cost-effectiveness of breast cancer screening for survivors of childhood cancer treated with chest radiation. Ann Intern Med. 2020;173:331-341.
- Saslow D, Boetes C, Burke W, et al; American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast cancer screening and diagnosis version 1.2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed September 25, 2020.
- Bharucha PP, Chiu KE, Francois FM, et al. Genetic testing and screening recommendations for patients with hereditary breast cancer. RadioGraphics. 2020;40:913-936.
- Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29:2327-2333.
- Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230-3235.
- American College of Obstetricians and Gynecologists. Committee opinion no. 625: management of women with dense breasts diagnosed by mammography [published correction appears in Obstet Gynecol. 2016;127:166]. Obstet Gynecol. 2015;125(3):750-751.
- Bharucha PP, Chiu KE, Francois FM, et al. Genetic testing and screening recommendations for patients with hereditary breast cancer. RadioGraphics. 2020;40:913-936.
- Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29:2327-2333.
- Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230-3235.
- American College of Obstetricians and Gynecologists. Committee opinion no. 625: management of women with dense breasts diagnosed by mammography [published correction appears in Obstet Gynecol. 2016;127:166]. Obstet Gynecol. 2015;125(3):750-751.
