Breast Cancer

Adoption of the 21-gene recurrence score (RS) assay does not appear to have decreased chemotherapy use overall among Medicare beneficiaries diagnosed with breast cancer, investigators reported online in JAMA Oncology. However, use of the assay was associated with decreased chemotherapy use in high-risk patients and increased chemotherapy use in low-risk patients in the retrospective study.

“Contrary to our hypothesis, we did not observe a change in chemotherapy use in the overall study population after the adoption of the RS assay between 2005 and 2009 or a general association between receipt of chemotherapy and use of the assay in multivariable analyses or HRR [hospital referral region]–level analyses,” Dr. Michaela Dinan of the Duke Clinical Research Institute and her associates wrote (JAMA Oncol. doi: 10.1001/jamaoncol.2015.2722).

©ktsimage/Thinkstock.com

There was, however, an interaction between use of the Oncotype DX recurrence score (RS) assay and National Comprehensive Cancer Network (NCCN) risk category.

RS use was associated with lower chemotherapy use in women with high-risk disease (odds ratio, 0.34; 99% confidence interval, 0.20-0.57) and higher chemotherapy use in those with low-risk disease (OR, 4.46; 99% CI, 3.15-6.31).

NCCN guidelines recommend considering chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer for all but the smallest tumors.

The 21-gene Oncotype DX assay was one of the first gene expression profile tests to reach the market, and studies have suggested its use could save money by guiding allocation of chemotherapy to patients most likely to benefit.

An earlier multicenter NCCN database analysis reported an association between the progressive rise in RS testing and an overall decline in adjuvant chemotherapy in hormone-receptive breast cancers diagnosed between 2006 and 2008.

The current study took a wider look at use of the RS assay and chemotherapy using a nationally representative sample of 44,044 women, aged 65 years and older, diagnosed with early-stage, ER-positive breast cancer between 2005 and 2009 in the SEER (Surveillance, Epidemiology, and End Results) database linked with Medicare claims. Of these, 24% had low-risk, 51.3% intermediate-risk, and 24.6% high-risk disease based on NCCN criteria. Roughly a quarter were node positive.

Use of the RS assay was higher among patients 70 years or younger, patients with fewer comorbid conditions, and patients with T1c tumors, node-negative disease, and intermediate-risk disease, Dr. Dinan and associates reported.

In all, 14.3% of patients overall and 26.5% of patients 70 years or younger received chemotherapy within 12 months of diagnosis, “which supports a significant influence of age on chemotherapy use,” they said.

“Our data suggest that use of the RS assay may have decreased chemotherapy use in general practice among younger patients with high-risk disease in whom receipt of chemotherapy would have otherwise been likely but that it was associated with greater chemotherapy use in patients with low-risk disease. The impact of the RS assay on chemotherapy use is likely population dependent and is influenced by the population’s pretest likelihood of undergoing chemotherapy,” they concluded.

The authors acknowledge that the study had limitations as only RS assays paid for by Medicare were analyzed, HER2 status was unavailable, and patients in the SEER registry are more likely to be nonwhite and live in high-poverty and urban areas, which may affect generalizability.

The study was sponsored by a grant from the Agency for Healthcare Research and Quality. The authors reported having no conflicts of interests. Dr. Kurian and Dr. Friese reported receiving funding from a National Cancer Institute grant to the University of Michigan.

[email protected]

On Twitter @pwendl

Adoption of the 21-gene recurrence score (RS) assay does not appear to have decreased chemotherapy use overall among Medicare beneficiaries diagnosed with breast cancer, investigators reported online in JAMA Oncology. However, use of the assay was associated with decreased chemotherapy use in high-risk patients and increased chemotherapy use in low-risk patients in the retrospective study.

“Contrary to our hypothesis, we did not observe a change in chemotherapy use in the overall study population after the adoption of the RS assay between 2005 and 2009 or a general association between receipt of chemotherapy and use of the assay in multivariable analyses or HRR [hospital referral region]–level analyses,” Dr. Michaela Dinan of the Duke Clinical Research Institute and her associates wrote (JAMA Oncol. doi: 10.1001/jamaoncol.2015.2722).

©ktsimage/Thinkstock.com

There was, however, an interaction between use of the Oncotype DX recurrence score (RS) assay and National Comprehensive Cancer Network (NCCN) risk category.

RS use was associated with lower chemotherapy use in women with high-risk disease (odds ratio, 0.34; 99% confidence interval, 0.20-0.57) and higher chemotherapy use in those with low-risk disease (OR, 4.46; 99% CI, 3.15-6.31).

NCCN guidelines recommend considering chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer for all but the smallest tumors.

The 21-gene Oncotype DX assay was one of the first gene expression profile tests to reach the market, and studies have suggested its use could save money by guiding allocation of chemotherapy to patients most likely to benefit.

An earlier multicenter NCCN database analysis reported an association between the progressive rise in RS testing and an overall decline in adjuvant chemotherapy in hormone-receptive breast cancers diagnosed between 2006 and 2008.

The current study took a wider look at use of the RS assay and chemotherapy using a nationally representative sample of 44,044 women, aged 65 years and older, diagnosed with early-stage, ER-positive breast cancer between 2005 and 2009 in the SEER (Surveillance, Epidemiology, and End Results) database linked with Medicare claims. Of these, 24% had low-risk, 51.3% intermediate-risk, and 24.6% high-risk disease based on NCCN criteria. Roughly a quarter were node positive.

Use of the RS assay was higher among patients 70 years or younger, patients with fewer comorbid conditions, and patients with T1c tumors, node-negative disease, and intermediate-risk disease, Dr. Dinan and associates reported.

In all, 14.3% of patients overall and 26.5% of patients 70 years or younger received chemotherapy within 12 months of diagnosis, “which supports a significant influence of age on chemotherapy use,” they said.

“Our data suggest that use of the RS assay may have decreased chemotherapy use in general practice among younger patients with high-risk disease in whom receipt of chemotherapy would have otherwise been likely but that it was associated with greater chemotherapy use in patients with low-risk disease. The impact of the RS assay on chemotherapy use is likely population dependent and is influenced by the population’s pretest likelihood of undergoing chemotherapy,” they concluded.

The authors acknowledge that the study had limitations as only RS assays paid for by Medicare were analyzed, HER2 status was unavailable, and patients in the SEER registry are more likely to be nonwhite and live in high-poverty and urban areas, which may affect generalizability.

The study was sponsored by a grant from the Agency for Healthcare Research and Quality. The authors reported having no conflicts of interests. Dr. Kurian and Dr. Friese reported receiving funding from a National Cancer Institute grant to the University of Michigan.

[email protected]

On Twitter @pwendl

Adoption of the 21-gene recurrence score (RS) assay does not appear to have decreased chemotherapy use overall among Medicare beneficiaries diagnosed with breast cancer, investigators reported online in JAMA Oncology. However, use of the assay was associated with decreased chemotherapy use in high-risk patients and increased chemotherapy use in low-risk patients in the retrospective study.

“Contrary to our hypothesis, we did not observe a change in chemotherapy use in the overall study population after the adoption of the RS assay between 2005 and 2009 or a general association between receipt of chemotherapy and use of the assay in multivariable analyses or HRR [hospital referral region]–level analyses,” Dr. Michaela Dinan of the Duke Clinical Research Institute and her associates wrote (JAMA Oncol. doi: 10.1001/jamaoncol.2015.2722).

©ktsimage/Thinkstock.com

There was, however, an interaction between use of the Oncotype DX recurrence score (RS) assay and National Comprehensive Cancer Network (NCCN) risk category.

RS use was associated with lower chemotherapy use in women with high-risk disease (odds ratio, 0.34; 99% confidence interval, 0.20-0.57) and higher chemotherapy use in those with low-risk disease (OR, 4.46; 99% CI, 3.15-6.31).

NCCN guidelines recommend considering chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer for all but the smallest tumors.

The 21-gene Oncotype DX assay was one of the first gene expression profile tests to reach the market, and studies have suggested its use could save money by guiding allocation of chemotherapy to patients most likely to benefit.

An earlier multicenter NCCN database analysis reported an association between the progressive rise in RS testing and an overall decline in adjuvant chemotherapy in hormone-receptive breast cancers diagnosed between 2006 and 2008.

The current study took a wider look at use of the RS assay and chemotherapy using a nationally representative sample of 44,044 women, aged 65 years and older, diagnosed with early-stage, ER-positive breast cancer between 2005 and 2009 in the SEER (Surveillance, Epidemiology, and End Results) database linked with Medicare claims. Of these, 24% had low-risk, 51.3% intermediate-risk, and 24.6% high-risk disease based on NCCN criteria. Roughly a quarter were node positive.

Use of the RS assay was higher among patients 70 years or younger, patients with fewer comorbid conditions, and patients with T1c tumors, node-negative disease, and intermediate-risk disease, Dr. Dinan and associates reported.

In all, 14.3% of patients overall and 26.5% of patients 70 years or younger received chemotherapy within 12 months of diagnosis, “which supports a significant influence of age on chemotherapy use,” they said.

“Our data suggest that use of the RS assay may have decreased chemotherapy use in general practice among younger patients with high-risk disease in whom receipt of chemotherapy would have otherwise been likely but that it was associated with greater chemotherapy use in patients with low-risk disease. The impact of the RS assay on chemotherapy use is likely population dependent and is influenced by the population’s pretest likelihood of undergoing chemotherapy,” they concluded.

The authors acknowledge that the study had limitations as only RS assays paid for by Medicare were analyzed, HER2 status was unavailable, and patients in the SEER registry are more likely to be nonwhite and live in high-poverty and urban areas, which may affect generalizability.

The study was sponsored by a grant from the Agency for Healthcare Research and Quality. The authors reported having no conflicts of interests. Dr. Kurian and Dr. Friese reported receiving funding from a National Cancer Institute grant to the University of Michigan.

[email protected]

On Twitter @pwendl

HOUSTON – There are at least three evidence-based practices for reducing the costs of locoregional therapy for early breast cancer without compromising the quality of care, according to Dr. Rachel Adams Greenup of the department of surgery at Duke University Medical Center, in Durham, North Carolina.

Management of axilla per the ACOSOG Z0011 study, adherence to joint Society of Surgical Oncology/American Society of Radiation Oncology (SSO/ASTRO) margin guidelines, and alternative radiation regimens following lumpectomy can all cut costs without compromsing quality of care, she said at the annual Society of Surgical Oncology Symposium.

The results of ACOSOG Z0011, published in 2010, were universally acknowledged to be practice changing. They showed that for women undergoing lumpectomy and radiation therapy for T1-2 invasive breast cancer and positive sentinel lymph node biopsy, completion axiallary dissection did not improve either disease-free or overall survival (DFS/OS). There were low rates of locoregional recurrence regardless of whether patients received axillary node dissection.

The potential savings from eliminating the routine practice of axillary dissection were estimated to be a 64% reduction in inpatient days, and an 18% decrease in perioperative costs.

The SSO/ASTRO margin guidelines, published in 2014, were developed by a multidisciplinary panel based on a meta-analysis of 33 studies involving more than 28,000 patients. The guidelines note that positive surgical margins are associated with a 2-fold increase in ipsilateral breast tumor recurrence, with “no ink on tumor” sufficient for a negative margin. The guidelines say that further margin width resections do not decrease same-breast recurrences.

In a related analysis of the cost implications, Dr. Greenup and colleagues noted that there are wide variations in clinical practice, and that 20% of women with close but negative margins were re-excised needlessly. Eliminating 25,000 unnecessary re-excisions annually would save $31 million dollars. These savings do not include cost reductions from an estimated 8% to 12% reduction in conversions to mastectomy that would be avoided, the authors calculated.

The costs of radiation following lumpectomy correlate directly with the number of delivered radiation fractions or treatment sessions, and also with the technique. Alternatives to standard radiation schedules include the following:

Per-patient costs for each of these options in 2011 ranged from $0 for no radiation, as in CALGB 9343, to $5342 for APBI, $9122 for HF-WBI, and $13m358 for conventionally fractionated WBI.

Dr Greenup and colleagues looked at data on 43,247 women in the National Cancer Data Base with T1-T2, NO invasive breast cancers treated with lumpectomy, and compared the actual costs of treatment with the evidence-based alternative. They found that 26% of patients were treated with the least cost-effective radiation, while nearly all of the remaining patients received more expensive radiation than necessary. If every patient were treated with the most cost-effective approach, there would be an estimated 39% reduction in costs, translating into a saving of $164 million over a single year, they reported in an abstract presented at the 2014 San Antonio Breast Cancer Symposium.

“We can’t make decisions based on cost alone, and value is certainly more important, but clinical trials, moving forward, should incorporate cost information. There is an opportunity to have small changes in clinical practice have the potential to make dramatic reductions in health care spending, and there are lots of opportunities in early stage breast cancer to practice evidence-based care while reducing health care spending,” Dr. Greenup concluded.

Dr. Greenup reported having no relevant financial disclosures.

HOUSTON – There are at least three evidence-based practices for reducing the costs of locoregional therapy for early breast cancer without compromising the quality of care, according to Dr. Rachel Adams Greenup of the department of surgery at Duke University Medical Center, in Durham, North Carolina.

Management of axilla per the ACOSOG Z0011 study, adherence to joint Society of Surgical Oncology/American Society of Radiation Oncology (SSO/ASTRO) margin guidelines, and alternative radiation regimens following lumpectomy can all cut costs without compromsing quality of care, she said at the annual Society of Surgical Oncology Symposium.

The results of ACOSOG Z0011, published in 2010, were universally acknowledged to be practice changing. They showed that for women undergoing lumpectomy and radiation therapy for T1-2 invasive breast cancer and positive sentinel lymph node biopsy, completion axiallary dissection did not improve either disease-free or overall survival (DFS/OS). There were low rates of locoregional recurrence regardless of whether patients received axillary node dissection.

The potential savings from eliminating the routine practice of axillary dissection were estimated to be a 64% reduction in inpatient days, and an 18% decrease in perioperative costs.

The SSO/ASTRO margin guidelines, published in 2014, were developed by a multidisciplinary panel based on a meta-analysis of 33 studies involving more than 28,000 patients. The guidelines note that positive surgical margins are associated with a 2-fold increase in ipsilateral breast tumor recurrence, with “no ink on tumor” sufficient for a negative margin. The guidelines say that further margin width resections do not decrease same-breast recurrences.

In a related analysis of the cost implications, Dr. Greenup and colleagues noted that there are wide variations in clinical practice, and that 20% of women with close but negative margins were re-excised needlessly. Eliminating 25,000 unnecessary re-excisions annually would save $31 million dollars. These savings do not include cost reductions from an estimated 8% to 12% reduction in conversions to mastectomy that would be avoided, the authors calculated.

The costs of radiation following lumpectomy correlate directly with the number of delivered radiation fractions or treatment sessions, and also with the technique. Alternatives to standard radiation schedules include the following:

Per-patient costs for each of these options in 2011 ranged from $0 for no radiation, as in CALGB 9343, to $5342 for APBI, $9122 for HF-WBI, and $13m358 for conventionally fractionated WBI.

Dr Greenup and colleagues looked at data on 43,247 women in the National Cancer Data Base with T1-T2, NO invasive breast cancers treated with lumpectomy, and compared the actual costs of treatment with the evidence-based alternative. They found that 26% of patients were treated with the least cost-effective radiation, while nearly all of the remaining patients received more expensive radiation than necessary. If every patient were treated with the most cost-effective approach, there would be an estimated 39% reduction in costs, translating into a saving of $164 million over a single year, they reported in an abstract presented at the 2014 San Antonio Breast Cancer Symposium.

“We can’t make decisions based on cost alone, and value is certainly more important, but clinical trials, moving forward, should incorporate cost information. There is an opportunity to have small changes in clinical practice have the potential to make dramatic reductions in health care spending, and there are lots of opportunities in early stage breast cancer to practice evidence-based care while reducing health care spending,” Dr. Greenup concluded.

Dr. Greenup reported having no relevant financial disclosures.

HOUSTON – There are at least three evidence-based practices for reducing the costs of locoregional therapy for early breast cancer without compromising the quality of care, according to Dr. Rachel Adams Greenup of the department of surgery at Duke University Medical Center, in Durham, North Carolina.

Management of axilla per the ACOSOG Z0011 study, adherence to joint Society of Surgical Oncology/American Society of Radiation Oncology (SSO/ASTRO) margin guidelines, and alternative radiation regimens following lumpectomy can all cut costs without compromsing quality of care, she said at the annual Society of Surgical Oncology Symposium.

The results of ACOSOG Z0011, published in 2010, were universally acknowledged to be practice changing. They showed that for women undergoing lumpectomy and radiation therapy for T1-2 invasive breast cancer and positive sentinel lymph node biopsy, completion axiallary dissection did not improve either disease-free or overall survival (DFS/OS). There were low rates of locoregional recurrence regardless of whether patients received axillary node dissection.

The potential savings from eliminating the routine practice of axillary dissection were estimated to be a 64% reduction in inpatient days, and an 18% decrease in perioperative costs.

The SSO/ASTRO margin guidelines, published in 2014, were developed by a multidisciplinary panel based on a meta-analysis of 33 studies involving more than 28,000 patients. The guidelines note that positive surgical margins are associated with a 2-fold increase in ipsilateral breast tumor recurrence, with “no ink on tumor” sufficient for a negative margin. The guidelines say that further margin width resections do not decrease same-breast recurrences.

In a related analysis of the cost implications, Dr. Greenup and colleagues noted that there are wide variations in clinical practice, and that 20% of women with close but negative margins were re-excised needlessly. Eliminating 25,000 unnecessary re-excisions annually would save $31 million dollars. These savings do not include cost reductions from an estimated 8% to 12% reduction in conversions to mastectomy that would be avoided, the authors calculated.

The costs of radiation following lumpectomy correlate directly with the number of delivered radiation fractions or treatment sessions, and also with the technique. Alternatives to standard radiation schedules include the following:

Per-patient costs for each of these options in 2011 ranged from $0 for no radiation, as in CALGB 9343, to $5342 for APBI, $9122 for HF-WBI, and $13m358 for conventionally fractionated WBI.

Dr Greenup and colleagues looked at data on 43,247 women in the National Cancer Data Base with T1-T2, NO invasive breast cancers treated with lumpectomy, and compared the actual costs of treatment with the evidence-based alternative. They found that 26% of patients were treated with the least cost-effective radiation, while nearly all of the remaining patients received more expensive radiation than necessary. If every patient were treated with the most cost-effective approach, there would be an estimated 39% reduction in costs, translating into a saving of $164 million over a single year, they reported in an abstract presented at the 2014 San Antonio Breast Cancer Symposium.

“We can’t make decisions based on cost alone, and value is certainly more important, but clinical trials, moving forward, should incorporate cost information. There is an opportunity to have small changes in clinical practice have the potential to make dramatic reductions in health care spending, and there are lots of opportunities in early stage breast cancer to practice evidence-based care while reducing health care spending,” Dr. Greenup concluded.

Dr. Greenup reported having no relevant financial disclosures.

Radiotherapy after breast-conserving surgery for ductal carcinoma in situ reduces the risk of ipsilateral invasive recurrence but does not reduce breast cancer mortality, new research shows.

Analysis of data from 108,196 women diagnosed with ductal carcinoma in situ (DCIS), who were included in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, showed radiotherapy significantly reduced the risk of ipsilateral invasive recurrence at 10 years (adjusted hazard, 0.47; 95% confidence interval, 0.42-0.53; P less than .001) but only achieved a nonsignificant reduction in breast cancer mortality (adjusted HR, 0.81; 95% CI, 0.63-1.04; P = .10).

“The finding of greatest clinical importance was that prevention of ipsilateral invasive recurrence did not prevent death from breast cancer,” wrote Dr. Steven A. Narod and his colleagues from the Women’s College Hospital and the University of Toronto.

Though it is often stated that DCIS is a preinvasive neoplastic lesion that is not lethal in itself, these results suggest that this interpretation should be revisited, they said in the report, published online August 20 in JAMA Oncology.

“Some cases of DCIS have an inherent potential for distant metastatic spread. It is therefore appropriate to consider these as de facto breast cancers and not as preinvasive markers predictive of a subsequent invasive cancer,” they said.

KGH/Wikimedia Commons/CC BY-SA

The mean age at diagnosis of DCIS for the women in the database was 53.8 (range, 15-69) years, and the mean duration of follow-up was 7.5 (range, 0-23.9) years. Overall, the 20-year breast cancer–specific mortality rate following a diagnosis of DCIS was 3.3% (95% CI, 3.0%-3.6%).

Just over 1% of the 42,250 women treated with lumpectomy and radiotherapy developed an ipsilateral invasive recurrence in the follow-up period and 163 women (0.4%) died of breast cancer. Of the 19,762 women who were treated with lumpectomy without radiotherapy, 595 women (3%) developed an ipsilateral invasive recurrence and 102 women (0.5%) died of breast cancer, Dr. Narod and his associates reported (JAMA Oncology. 2015 Aug. 20 doi: 10.1001/jamaoncol.2015.2510).

Among the 956 women who died of breast cancer in the follow-up period, over half (517) did not experience an in-breast invasive recurrence prior to death. Of the 163 women who were treated with lumpectomy and radiotherapy and then died of breast cancer, 57.7% (94) did not experience an in-breast invasive recurrence prior to death. Among the 102 women treated with lumpectomy without radiotherapy who died of breast cancer, 51 did not experience an in-breast invasive recurrence prior to death (50.0%). Among the 154 women treated with a mastectomy (unilateral or bilateral) who died of breast cancer, 112 did not experience an in-breast invasive recurrence prior to death (72.7%), the investigators reported.

They found that young age at diagnosis and black ethnicity were predictors of breast cancer mortality. Young women diagnosed with ductal carcinoma in situ before the age of 35 years had a more than twofold greater risk of dying from breast cancer than older women (7.8% vs. 3.2%; HR 2.58, 95% CI, 1.85-3.60; P less than .001). Black women also had a much greater risk of dying from breast cancer than non-Hispanic whites (7.0% vs. 3.0%; HR, 2.55, 95% CI, 2.17-3.01; P less than .001).

“If DCIS were truly a (noninvasive) precursor of breast cancer, then a woman with DCIS should not die of breast cancer without first experiencing an invasive breast cancer (ipsilateral or contralateral), and the prevention of an invasive recurrence should prevent her death from breast cancer. Surprisingly, the majority of women with DCIS in the cohort who died of breast cancer did not experience an invasive in-breast recurrence (ipsilateral or contralateral) prior to death (54.1%),” the investigators said.

“The outcome of breast cancer mortality for DCIS patients is of importance in itself and potential treatments that affect mortality are deserving of study,” they concluded.

No relevant conflicts of interest were declared.

Radiotherapy after breast-conserving surgery for ductal carcinoma in situ reduces the risk of ipsilateral invasive recurrence but does not reduce breast cancer mortality, new research shows.

Analysis of data from 108,196 women diagnosed with ductal carcinoma in situ (DCIS), who were included in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, showed radiotherapy significantly reduced the risk of ipsilateral invasive recurrence at 10 years (adjusted hazard, 0.47; 95% confidence interval, 0.42-0.53; P less than .001) but only achieved a nonsignificant reduction in breast cancer mortality (adjusted HR, 0.81; 95% CI, 0.63-1.04; P = .10).

“The finding of greatest clinical importance was that prevention of ipsilateral invasive recurrence did not prevent death from breast cancer,” wrote Dr. Steven A. Narod and his colleagues from the Women’s College Hospital and the University of Toronto.

Though it is often stated that DCIS is a preinvasive neoplastic lesion that is not lethal in itself, these results suggest that this interpretation should be revisited, they said in the report, published online August 20 in JAMA Oncology.

“Some cases of DCIS have an inherent potential for distant metastatic spread. It is therefore appropriate to consider these as de facto breast cancers and not as preinvasive markers predictive of a subsequent invasive cancer,” they said.

KGH/Wikimedia Commons/CC BY-SA

The mean age at diagnosis of DCIS for the women in the database was 53.8 (range, 15-69) years, and the mean duration of follow-up was 7.5 (range, 0-23.9) years. Overall, the 20-year breast cancer–specific mortality rate following a diagnosis of DCIS was 3.3% (95% CI, 3.0%-3.6%).

Just over 1% of the 42,250 women treated with lumpectomy and radiotherapy developed an ipsilateral invasive recurrence in the follow-up period and 163 women (0.4%) died of breast cancer. Of the 19,762 women who were treated with lumpectomy without radiotherapy, 595 women (3%) developed an ipsilateral invasive recurrence and 102 women (0.5%) died of breast cancer, Dr. Narod and his associates reported (JAMA Oncology. 2015 Aug. 20 doi: 10.1001/jamaoncol.2015.2510).

Among the 956 women who died of breast cancer in the follow-up period, over half (517) did not experience an in-breast invasive recurrence prior to death. Of the 163 women who were treated with lumpectomy and radiotherapy and then died of breast cancer, 57.7% (94) did not experience an in-breast invasive recurrence prior to death. Among the 102 women treated with lumpectomy without radiotherapy who died of breast cancer, 51 did not experience an in-breast invasive recurrence prior to death (50.0%). Among the 154 women treated with a mastectomy (unilateral or bilateral) who died of breast cancer, 112 did not experience an in-breast invasive recurrence prior to death (72.7%), the investigators reported.

They found that young age at diagnosis and black ethnicity were predictors of breast cancer mortality. Young women diagnosed with ductal carcinoma in situ before the age of 35 years had a more than twofold greater risk of dying from breast cancer than older women (7.8% vs. 3.2%; HR 2.58, 95% CI, 1.85-3.60; P less than .001). Black women also had a much greater risk of dying from breast cancer than non-Hispanic whites (7.0% vs. 3.0%; HR, 2.55, 95% CI, 2.17-3.01; P less than .001).

“If DCIS were truly a (noninvasive) precursor of breast cancer, then a woman with DCIS should not die of breast cancer without first experiencing an invasive breast cancer (ipsilateral or contralateral), and the prevention of an invasive recurrence should prevent her death from breast cancer. Surprisingly, the majority of women with DCIS in the cohort who died of breast cancer did not experience an invasive in-breast recurrence (ipsilateral or contralateral) prior to death (54.1%),” the investigators said.

“The outcome of breast cancer mortality for DCIS patients is of importance in itself and potential treatments that affect mortality are deserving of study,” they concluded.

No relevant conflicts of interest were declared.

Radiotherapy after breast-conserving surgery for ductal carcinoma in situ reduces the risk of ipsilateral invasive recurrence but does not reduce breast cancer mortality, new research shows.

Analysis of data from 108,196 women diagnosed with ductal carcinoma in situ (DCIS), who were included in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, showed radiotherapy significantly reduced the risk of ipsilateral invasive recurrence at 10 years (adjusted hazard, 0.47; 95% confidence interval, 0.42-0.53; P less than .001) but only achieved a nonsignificant reduction in breast cancer mortality (adjusted HR, 0.81; 95% CI, 0.63-1.04; P = .10).

“The finding of greatest clinical importance was that prevention of ipsilateral invasive recurrence did not prevent death from breast cancer,” wrote Dr. Steven A. Narod and his colleagues from the Women’s College Hospital and the University of Toronto.

Though it is often stated that DCIS is a preinvasive neoplastic lesion that is not lethal in itself, these results suggest that this interpretation should be revisited, they said in the report, published online August 20 in JAMA Oncology.

“Some cases of DCIS have an inherent potential for distant metastatic spread. It is therefore appropriate to consider these as de facto breast cancers and not as preinvasive markers predictive of a subsequent invasive cancer,” they said.

KGH/Wikimedia Commons/CC BY-SA

The mean age at diagnosis of DCIS for the women in the database was 53.8 (range, 15-69) years, and the mean duration of follow-up was 7.5 (range, 0-23.9) years. Overall, the 20-year breast cancer–specific mortality rate following a diagnosis of DCIS was 3.3% (95% CI, 3.0%-3.6%).

Just over 1% of the 42,250 women treated with lumpectomy and radiotherapy developed an ipsilateral invasive recurrence in the follow-up period and 163 women (0.4%) died of breast cancer. Of the 19,762 women who were treated with lumpectomy without radiotherapy, 595 women (3%) developed an ipsilateral invasive recurrence and 102 women (0.5%) died of breast cancer, Dr. Narod and his associates reported (JAMA Oncology. 2015 Aug. 20 doi: 10.1001/jamaoncol.2015.2510).

Among the 956 women who died of breast cancer in the follow-up period, over half (517) did not experience an in-breast invasive recurrence prior to death. Of the 163 women who were treated with lumpectomy and radiotherapy and then died of breast cancer, 57.7% (94) did not experience an in-breast invasive recurrence prior to death. Among the 102 women treated with lumpectomy without radiotherapy who died of breast cancer, 51 did not experience an in-breast invasive recurrence prior to death (50.0%). Among the 154 women treated with a mastectomy (unilateral or bilateral) who died of breast cancer, 112 did not experience an in-breast invasive recurrence prior to death (72.7%), the investigators reported.

They found that young age at diagnosis and black ethnicity were predictors of breast cancer mortality. Young women diagnosed with ductal carcinoma in situ before the age of 35 years had a more than twofold greater risk of dying from breast cancer than older women (7.8% vs. 3.2%; HR 2.58, 95% CI, 1.85-3.60; P less than .001). Black women also had a much greater risk of dying from breast cancer than non-Hispanic whites (7.0% vs. 3.0%; HR, 2.55, 95% CI, 2.17-3.01; P less than .001).

“If DCIS were truly a (noninvasive) precursor of breast cancer, then a woman with DCIS should not die of breast cancer without first experiencing an invasive breast cancer (ipsilateral or contralateral), and the prevention of an invasive recurrence should prevent her death from breast cancer. Surprisingly, the majority of women with DCIS in the cohort who died of breast cancer did not experience an invasive in-breast recurrence (ipsilateral or contralateral) prior to death (54.1%),” the investigators said.

“The outcome of breast cancer mortality for DCIS patients is of importance in itself and potential treatments that affect mortality are deserving of study,” they concluded.

No relevant conflicts of interest were declared.

A group-based behavioral weight loss program supplemented with personal contact and support was effective in helping overweight or obese breast cancer survivors lose a clinically meaningful amount of weight, investigators reported online Aug. 17 in the Journal of Clinical Oncology.

“Women who have been diagnosed and treated for breast cancer often have special issues and problems, such as treatment-related adverse effects, fatigue, and depression, that can complicate weight management efforts,” wrote Cheryl L. Rock, Ph.D., of the University of California, San Diego, Moores Cancer Center in La Jolla, and her colleagues.

©kaspiic/thinkstockphotos.com

The results from this trial demonstrate that weight loss, even though it was modest, and increased physical activity can be achieved in this population and suggest that these issues can be overcome, the authors noted.

The multicenter trial included 692 overweight or obese breast cancer survivors who were randomly assigned to either the intervention group – which included a cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance – or a control group with a less intensive intervention (J Clin Oncol. 2015 Aug. 17 doi: 10.1200/JCO.2015.61.1095).

At 6 months, the mean weight loss in the intervention group was 5.9%; at 12 months, the weight loss held steady and was maintained at 6%. In the control group, weight loss was 1.3% at 6 months and 1.5% at 12 months.

At 18 months, the women in the intervention group were 4.7% below their baseline weight, and at 24 months they weighed 3.7% less than at entry into the study. Those in the control group were 1.3% below baseline weight at 18 months and 1.1% below at 24 months.

The weight loss intervention was more effective among women older than 55 years than in younger women, who may need counseling and resources beyond that offered in this study, to achieve sufficient weight loss, Dr. Rock and her associates added.

The study was supported by the National Cancer Institute and by a grant from the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research. Dr. Rock reported research funding from Jenny Craig and Nestle USA, and several of the coauthors reported financial relationships with various corporations.

A group-based behavioral weight loss program supplemented with personal contact and support was effective in helping overweight or obese breast cancer survivors lose a clinically meaningful amount of weight, investigators reported online Aug. 17 in the Journal of Clinical Oncology.

“Women who have been diagnosed and treated for breast cancer often have special issues and problems, such as treatment-related adverse effects, fatigue, and depression, that can complicate weight management efforts,” wrote Cheryl L. Rock, Ph.D., of the University of California, San Diego, Moores Cancer Center in La Jolla, and her colleagues.

©kaspiic/thinkstockphotos.com

The results from this trial demonstrate that weight loss, even though it was modest, and increased physical activity can be achieved in this population and suggest that these issues can be overcome, the authors noted.

The multicenter trial included 692 overweight or obese breast cancer survivors who were randomly assigned to either the intervention group – which included a cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance – or a control group with a less intensive intervention (J Clin Oncol. 2015 Aug. 17 doi: 10.1200/JCO.2015.61.1095).

At 6 months, the mean weight loss in the intervention group was 5.9%; at 12 months, the weight loss held steady and was maintained at 6%. In the control group, weight loss was 1.3% at 6 months and 1.5% at 12 months.

At 18 months, the women in the intervention group were 4.7% below their baseline weight, and at 24 months they weighed 3.7% less than at entry into the study. Those in the control group were 1.3% below baseline weight at 18 months and 1.1% below at 24 months.

The weight loss intervention was more effective among women older than 55 years than in younger women, who may need counseling and resources beyond that offered in this study, to achieve sufficient weight loss, Dr. Rock and her associates added.

The study was supported by the National Cancer Institute and by a grant from the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research. Dr. Rock reported research funding from Jenny Craig and Nestle USA, and several of the coauthors reported financial relationships with various corporations.

A group-based behavioral weight loss program supplemented with personal contact and support was effective in helping overweight or obese breast cancer survivors lose a clinically meaningful amount of weight, investigators reported online Aug. 17 in the Journal of Clinical Oncology.

“Women who have been diagnosed and treated for breast cancer often have special issues and problems, such as treatment-related adverse effects, fatigue, and depression, that can complicate weight management efforts,” wrote Cheryl L. Rock, Ph.D., of the University of California, San Diego, Moores Cancer Center in La Jolla, and her colleagues.

©kaspiic/thinkstockphotos.com

The results from this trial demonstrate that weight loss, even though it was modest, and increased physical activity can be achieved in this population and suggest that these issues can be overcome, the authors noted.

The multicenter trial included 692 overweight or obese breast cancer survivors who were randomly assigned to either the intervention group – which included a cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance – or a control group with a less intensive intervention (J Clin Oncol. 2015 Aug. 17 doi: 10.1200/JCO.2015.61.1095).

At 6 months, the mean weight loss in the intervention group was 5.9%; at 12 months, the weight loss held steady and was maintained at 6%. In the control group, weight loss was 1.3% at 6 months and 1.5% at 12 months.

At 18 months, the women in the intervention group were 4.7% below their baseline weight, and at 24 months they weighed 3.7% less than at entry into the study. Those in the control group were 1.3% below baseline weight at 18 months and 1.1% below at 24 months.

The weight loss intervention was more effective among women older than 55 years than in younger women, who may need counseling and resources beyond that offered in this study, to achieve sufficient weight loss, Dr. Rock and her associates added.

The study was supported by the National Cancer Institute and by a grant from the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research. Dr. Rock reported research funding from Jenny Craig and Nestle USA, and several of the coauthors reported financial relationships with various corporations.

WASHINGTON – An online decision aid can help premenopausal women with breast cancer make informed decisions about their treatment, investigators report.

“Web-based decision aids can be an important complement to clinical care, to help women and their families think about some of these very difficult decisions in a very short space of time,” said Dr. Claire Foster, a chartered health psychologist in the faculty of health sciences at the University of Southampton (England).

Decision aids can enhance understanding, reduce uncertainties, and support joint decision making by describing for patients and families the relative risks and benefits of treatment. Yet most such materials are aimed at older, often postmenopausal women, Dr. Foster noted at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Approximately 20% of women with breast cancer are diagnosed before menopause. These women tend to have poorer prognosis and high-risk disease, with larger, higher-grade tumors at the time of diagnosis. In addition, they are more likely to have estrogen-receptor–negative disease and more lymph node involvement than older women. Even with successful treatment, younger women have a greater lifetime risk of local recurrence, contralateral recurrence, and distant metastases.

Young women also have special concerns about body image, disruptions of work and family life, and fears about loss of fertility and early menopause.

Dr. Foster and colleagues first interviewed 32 women with a mean age at diagnosis of breast cancer of 34. They conducted in-depth semistructured interviews and focus groups to determine how to convey information about treatments and their consequences that would help the patients in making decisions about their care.

The sample consisted of 30 white and 2 black women. In all, 22% were single, 59% had children, and 33% reported a family history of breast cancer. The majority of patients (63%) had undergone mastectomy (75% of this group also had reconstruction), and the remainder had breast-conserving surgery.

During the interviews and focus groups, the women identified specific factors as being important in their decision making, including breast cancer type (hormone receptor negative or positive, or triple-negative disease), surgical treatment (mastectomy, breast-conserving procedures, immediate or delayed reconstruction), nonsurgical therapies (radiation, chemotherapy, hormonal therapy), effects on fertility and fertility preservation options, and factors related to hospitalization, nutrition and exercise, and activities of daily living.

Participants especially expressed concerns about the effects of treatment on fertility and about having to make rapid decisions with little time to think about options.

Based on the discussions, the investigators have developed and are pilot-testing an online decision aid for young women diagnosed with early-stage breast cancer.

In a similar project, Dr. Foster and colleagues are developing a genetic testing decision aid for young women that focuses on the special concerns of those who may be carriers or high-risk mutations such as BRCA1 and BRCA2.

The work is supported by the UK National Institute for Health Research for Patient Benefit Programme and Breast Cancer Campaign. The authors reported no conflicts of interest.

WASHINGTON – An online decision aid can help premenopausal women with breast cancer make informed decisions about their treatment, investigators report.

“Web-based decision aids can be an important complement to clinical care, to help women and their families think about some of these very difficult decisions in a very short space of time,” said Dr. Claire Foster, a chartered health psychologist in the faculty of health sciences at the University of Southampton (England).

Decision aids can enhance understanding, reduce uncertainties, and support joint decision making by describing for patients and families the relative risks and benefits of treatment. Yet most such materials are aimed at older, often postmenopausal women, Dr. Foster noted at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Approximately 20% of women with breast cancer are diagnosed before menopause. These women tend to have poorer prognosis and high-risk disease, with larger, higher-grade tumors at the time of diagnosis. In addition, they are more likely to have estrogen-receptor–negative disease and more lymph node involvement than older women. Even with successful treatment, younger women have a greater lifetime risk of local recurrence, contralateral recurrence, and distant metastases.

Young women also have special concerns about body image, disruptions of work and family life, and fears about loss of fertility and early menopause.

Dr. Foster and colleagues first interviewed 32 women with a mean age at diagnosis of breast cancer of 34. They conducted in-depth semistructured interviews and focus groups to determine how to convey information about treatments and their consequences that would help the patients in making decisions about their care.

The sample consisted of 30 white and 2 black women. In all, 22% were single, 59% had children, and 33% reported a family history of breast cancer. The majority of patients (63%) had undergone mastectomy (75% of this group also had reconstruction), and the remainder had breast-conserving surgery.

During the interviews and focus groups, the women identified specific factors as being important in their decision making, including breast cancer type (hormone receptor negative or positive, or triple-negative disease), surgical treatment (mastectomy, breast-conserving procedures, immediate or delayed reconstruction), nonsurgical therapies (radiation, chemotherapy, hormonal therapy), effects on fertility and fertility preservation options, and factors related to hospitalization, nutrition and exercise, and activities of daily living.

Participants especially expressed concerns about the effects of treatment on fertility and about having to make rapid decisions with little time to think about options.

Based on the discussions, the investigators have developed and are pilot-testing an online decision aid for young women diagnosed with early-stage breast cancer.

In a similar project, Dr. Foster and colleagues are developing a genetic testing decision aid for young women that focuses on the special concerns of those who may be carriers or high-risk mutations such as BRCA1 and BRCA2.

The work is supported by the UK National Institute for Health Research for Patient Benefit Programme and Breast Cancer Campaign. The authors reported no conflicts of interest.

WASHINGTON – An online decision aid can help premenopausal women with breast cancer make informed decisions about their treatment, investigators report.

“Web-based decision aids can be an important complement to clinical care, to help women and their families think about some of these very difficult decisions in a very short space of time,” said Dr. Claire Foster, a chartered health psychologist in the faculty of health sciences at the University of Southampton (England).

Decision aids can enhance understanding, reduce uncertainties, and support joint decision making by describing for patients and families the relative risks and benefits of treatment. Yet most such materials are aimed at older, often postmenopausal women, Dr. Foster noted at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Approximately 20% of women with breast cancer are diagnosed before menopause. These women tend to have poorer prognosis and high-risk disease, with larger, higher-grade tumors at the time of diagnosis. In addition, they are more likely to have estrogen-receptor–negative disease and more lymph node involvement than older women. Even with successful treatment, younger women have a greater lifetime risk of local recurrence, contralateral recurrence, and distant metastases.

Young women also have special concerns about body image, disruptions of work and family life, and fears about loss of fertility and early menopause.

Dr. Foster and colleagues first interviewed 32 women with a mean age at diagnosis of breast cancer of 34. They conducted in-depth semistructured interviews and focus groups to determine how to convey information about treatments and their consequences that would help the patients in making decisions about their care.

The sample consisted of 30 white and 2 black women. In all, 22% were single, 59% had children, and 33% reported a family history of breast cancer. The majority of patients (63%) had undergone mastectomy (75% of this group also had reconstruction), and the remainder had breast-conserving surgery.

During the interviews and focus groups, the women identified specific factors as being important in their decision making, including breast cancer type (hormone receptor negative or positive, or triple-negative disease), surgical treatment (mastectomy, breast-conserving procedures, immediate or delayed reconstruction), nonsurgical therapies (radiation, chemotherapy, hormonal therapy), effects on fertility and fertility preservation options, and factors related to hospitalization, nutrition and exercise, and activities of daily living.

Participants especially expressed concerns about the effects of treatment on fertility and about having to make rapid decisions with little time to think about options.

Based on the discussions, the investigators have developed and are pilot-testing an online decision aid for young women diagnosed with early-stage breast cancer.

In a similar project, Dr. Foster and colleagues are developing a genetic testing decision aid for young women that focuses on the special concerns of those who may be carriers or high-risk mutations such as BRCA1 and BRCA2.

The work is supported by the UK National Institute for Health Research for Patient Benefit Programme and Breast Cancer Campaign. The authors reported no conflicts of interest.

Case: Patient seeks clarification and next steps on her breast density classification
Your patient, a 51-year-old postmenopausal woman (G0P0) in good health, had an annual screening mammogram that showed no evidence of malignancy. She is white and has a mother with a history of breast cancer. She has never had a breast biopsy. Following the mammogram, she received a letter from the imaging center, stating:

She calls your office and asks, “What should I do next?”

Breasts are composed of fibrous, glandular, and adipose tissue. If the breasts contain a lot of fibrous and glandular tissue, and little adipose tissue, they are considered to be “dense.” Using mammography, the current standard is to report the density of breast tissue using 4 categories:

Dense breast tissue is defined to include the 2 categories heterogeneously dense and extremely dense.

Observational studies have reported that dense breast tissue is associated with an increased risk of breast cancer, and dense breast tissue makes it more difficult to detect breast cancer on mammography. According to data from the Breast Cancer Surveillance Consortium, among women aged 50 or older, the relative risk of breast cancer stratified by the 4 categories of breast density is 0.59, 1.00, 1.46, and 1.77, for almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense, respectively.¹ In one study, the sensitivity of mammography to detect breast cancer was 82% to 88% for women with nondense breasts and 62% to 69% in women with dense breasts.² These data have catalyzed investigators to explore the use of supplemental imaging to enhance cancer detection in women with dense breasts.

The link between breast density and breast cancer risk and reduced sensitivity of mammography also has catalyzed activists and legislators to champion breast density notification laws, which have passed in more than 20 states. These laws require facilities that perform mammography to notify women with dense breasts that this finding is associated with an increased risk of breast cancer and that dense breasts reduce the ability of mammography to detect cancer. In some states, the law mandates that women with dense breasts be offered supplemental ultrasound imaging and that insurers must cover the cost of the ultrasound studies. Many of the laws recommend that the patient discuss the situation with the clinician who ordered the mammogram.

When I first saw the recommendation for patients to contact me about how to manage dense breasts, my initial response was, “Who? Me?” I felt ill equipped to provide any useful advice and suspected that many of my patients knew more than I about this issue.

Based on a review of the evidence, my current clinical recommendation is outlined in the 2 options below, including a low-resource utilization option and a high-resource utilization option. For patients, physicians, and health systems that are concerned that excessive breast cancer screening tests might cause more harm than benefit, the identification of dense breasts on mammogram is unlikely to be a trigger to perform any additional testing. In this situation, the pragmatic low-resource option is most relevant.

Alternatively, for patients and physicians who strongly believe in the value of screening mammography (see “Utilize tomosynthesis digital mammography technology for your patients” below), a reasonable strategy is to recommend that women with dense breasts and an increased risk for breast cancer be offered supplemental imaging.

In this editorial I elaborate these 2 approaches to breast cancer screening in women with dense breasts.
 

A pragmatic, low-resource utilization screening approach for women with dense breasts
There are no published randomized clinical trials that provide high-quality evidence on what to do if dense breasts are identified on mammography.³ Authors of observational studies have evaluated the potential role of supplemental imaging, including ultrasound and magnetic resonance imaging (MRI), in the management of dense breast tissue (see “Supplemental breast cancer screening modalities” below). Supplemental imaging involves complex trade-offs, balancing the potential benefit of identifying occult early breast cancer lesions not identified by mammography with the risk of subjecting many women without cancer to additional testing and unnecessary biopsies.

A pragmatic, low-resource utilization plan for women with dense breasts involves emphasizing that mammography is the best available screening tool and that annual or biennial mammography is the foundation of all current approaches to breast cancer screening. Supplemental imaging is unnecessary with this approach because there is no evidence that it reduces breast cancer mortality. There is, however, substantial evidence that using supplemental imaging for all women with dense breasts will result in little benefit and great costs, including many unnecessary biopsies.^1,4 Women with dense breasts also could consider annual clinical breast examination.

 

A high-resource utilization screening approach
There are no randomized trials to help guide recommendations about how to respond to a finding of dense breasts on mammography. In addition to breast density, many factors influence breast cancer risk, including a patient’s:

Women with both dense breasts and an increased risk of breast cancer may reap the greatest benefit from supplemental imaging, such as ultrasonography. Therefore, a two-step approach can help.

Step 1: Assess breast cancer risk. This can be accomplished using one of many calculators. Three that are commonly used are the:

The BCSC calculator uses age, race/ethnicity, first-degree relatives with breast cancer, a history of a breast biopsy, and breast density to calculate a 5-year risk of developing breast cancer.

The BCRAT tool uses current age, race/ethnicity, age at menarche, age at first live-birth of a child, number of first-degree relatives with breast cancer, a history of breast biopsies, and the identification of atypical hyperplasia to calculate a 5-year risk of breast cancer.

The IBIS model uses many more variables, including a detailed family history to calculate a 10-year and lifetime risk of breast cancer. If a patient has ductal carcinoma in situ, lobular carcinoma in situ, chest irradiation before age 30 years, or known BRCA1 or BRCA2 mutations, she is instructed not to use the risk calculators because they are at very high risk for breast cancer, and they need an individualized intensive plan for monitoring and prevention (see MRI section in “Supplemental breast cancer screening modalities” above).

Step 2: Use breast density and breast cancer risk to develop a screening plan. The NIH Breast Cancer Surveillance Consortium has published data estimating the risk that a woman with a mammogram negative for cancer will develop breast cancer within the next 12 months (based on her age, breast density, and breast cancer risk—calculated with the BCSC tool).⁸

It reported an increased risk of breast cancer diagnosed within 12 months following a mammogram that was negative for cancer in women with extremely dense breasts and a BCSC 5-year risk of breast cancer of 1.67% or greater and in women with heterogeneously dense breasts and a BCSC 5-year risk of breast cancer of 2.5% or greater.⁸

Using these cutoffs it is estimated that 24% of all women with heterogeneously or extremely dense breasts would be offered supplemental screening with a modality such as ultrasound, and 76% would be guided not to have supplemental screening because their risk of developing breast cancer in the 12 months following their negative mammogram is low.

If this guidance is followed, it would require 694 supplemental ultrasound studies and many biopsies to detect 1 additional breast cancer, significantly increasing overall health care costs.⁸ In many states insurers do not cover supplemental ultrasound imaging of the breasts. In most states insurers require preauthorization for supplemental MRI of the breasts. You need to know the insurance practices in the state to help guide decision making about supplemental imaging. The approach described above is consistent with the American College of Obstetricians and Gynecologists recommendation that women with dense breasts, who are asymptomaticand have no additional risk factors for breast cancer, do not need to be offered supplemental imaging.⁹

Case: Next steps
The BCSC calculator reveals that the 51-year-old woman with a family history of breast cancer and a mammogram showing extremely dense breasts has a 5-year risk of breast cancer of 2.68%. Given that this risk is elevated, this patient could be offered supplemental ultrasound screening and annual breast clinical examination. In addition, she could be further counseled about breast cancer chemoprevention options.¹⁰

Women with a strong family history of breast and/or ovarian cancer also could be referred for genetic counseling and BRCA testing.¹¹ The risk of having a BRCA mutation can be calculated using the BRCAPRO tool.¹²

Most women with dense breast tissue on mammography will never develop breast cancer. Yet the presence of dense breast tissue both increases the risk of breast cancer and decreases the sensitivity of mammography to detect cancer. There are no high-quality data from randomized trials to help guide our recommendations concerning the management of dense breasts identified on mammography. Yet many states have laws that suggest patients ask you to provide advice about breast density.

Patients, clinicians, and health systems vary in their confidence in the clinical value of breast cancer screening programs. Consequently, there is no “right answer” to this vexing problem. The standard of care is to support a range of options tailored to the specific clinical characteristics and needs of each patient. 
 

Case: Patient seeks clarification and next steps on her breast density classification
Your patient, a 51-year-old postmenopausal woman (G0P0) in good health, had an annual screening mammogram that showed no evidence of malignancy. She is white and has a mother with a history of breast cancer. She has never had a breast biopsy. Following the mammogram, she received a letter from the imaging center, stating:

She calls your office and asks, “What should I do next?”

Breasts are composed of fibrous, glandular, and adipose tissue. If the breasts contain a lot of fibrous and glandular tissue, and little adipose tissue, they are considered to be “dense.” Using mammography, the current standard is to report the density of breast tissue using 4 categories:

Dense breast tissue is defined to include the 2 categories heterogeneously dense and extremely dense.

Observational studies have reported that dense breast tissue is associated with an increased risk of breast cancer, and dense breast tissue makes it more difficult to detect breast cancer on mammography. According to data from the Breast Cancer Surveillance Consortium, among women aged 50 or older, the relative risk of breast cancer stratified by the 4 categories of breast density is 0.59, 1.00, 1.46, and 1.77, for almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense, respectively.¹ In one study, the sensitivity of mammography to detect breast cancer was 82% to 88% for women with nondense breasts and 62% to 69% in women with dense breasts.² These data have catalyzed investigators to explore the use of supplemental imaging to enhance cancer detection in women with dense breasts.

The link between breast density and breast cancer risk and reduced sensitivity of mammography also has catalyzed activists and legislators to champion breast density notification laws, which have passed in more than 20 states. These laws require facilities that perform mammography to notify women with dense breasts that this finding is associated with an increased risk of breast cancer and that dense breasts reduce the ability of mammography to detect cancer. In some states, the law mandates that women with dense breasts be offered supplemental ultrasound imaging and that insurers must cover the cost of the ultrasound studies. Many of the laws recommend that the patient discuss the situation with the clinician who ordered the mammogram.

When I first saw the recommendation for patients to contact me about how to manage dense breasts, my initial response was, “Who? Me?” I felt ill equipped to provide any useful advice and suspected that many of my patients knew more than I about this issue.

Based on a review of the evidence, my current clinical recommendation is outlined in the 2 options below, including a low-resource utilization option and a high-resource utilization option. For patients, physicians, and health systems that are concerned that excessive breast cancer screening tests might cause more harm than benefit, the identification of dense breasts on mammogram is unlikely to be a trigger to perform any additional testing. In this situation, the pragmatic low-resource option is most relevant.

Alternatively, for patients and physicians who strongly believe in the value of screening mammography (see “Utilize tomosynthesis digital mammography technology for your patients” below), a reasonable strategy is to recommend that women with dense breasts and an increased risk for breast cancer be offered supplemental imaging.

In this editorial I elaborate these 2 approaches to breast cancer screening in women with dense breasts.
 

A pragmatic, low-resource utilization screening approach for women with dense breasts
There are no published randomized clinical trials that provide high-quality evidence on what to do if dense breasts are identified on mammography.³ Authors of observational studies have evaluated the potential role of supplemental imaging, including ultrasound and magnetic resonance imaging (MRI), in the management of dense breast tissue (see “Supplemental breast cancer screening modalities” below). Supplemental imaging involves complex trade-offs, balancing the potential benefit of identifying occult early breast cancer lesions not identified by mammography with the risk of subjecting many women without cancer to additional testing and unnecessary biopsies.

A pragmatic, low-resource utilization plan for women with dense breasts involves emphasizing that mammography is the best available screening tool and that annual or biennial mammography is the foundation of all current approaches to breast cancer screening. Supplemental imaging is unnecessary with this approach because there is no evidence that it reduces breast cancer mortality. There is, however, substantial evidence that using supplemental imaging for all women with dense breasts will result in little benefit and great costs, including many unnecessary biopsies.^1,4 Women with dense breasts also could consider annual clinical breast examination.

 

A high-resource utilization screening approach
There are no randomized trials to help guide recommendations about how to respond to a finding of dense breasts on mammography. In addition to breast density, many factors influence breast cancer risk, including a patient’s:

Women with both dense breasts and an increased risk of breast cancer may reap the greatest benefit from supplemental imaging, such as ultrasonography. Therefore, a two-step approach can help.

Step 1: Assess breast cancer risk. This can be accomplished using one of many calculators. Three that are commonly used are the:

The BCSC calculator uses age, race/ethnicity, first-degree relatives with breast cancer, a history of a breast biopsy, and breast density to calculate a 5-year risk of developing breast cancer.

The BCRAT tool uses current age, race/ethnicity, age at menarche, age at first live-birth of a child, number of first-degree relatives with breast cancer, a history of breast biopsies, and the identification of atypical hyperplasia to calculate a 5-year risk of breast cancer.

The IBIS model uses many more variables, including a detailed family history to calculate a 10-year and lifetime risk of breast cancer. If a patient has ductal carcinoma in situ, lobular carcinoma in situ, chest irradiation before age 30 years, or known BRCA1 or BRCA2 mutations, she is instructed not to use the risk calculators because they are at very high risk for breast cancer, and they need an individualized intensive plan for monitoring and prevention (see MRI section in “Supplemental breast cancer screening modalities” above).

Step 2: Use breast density and breast cancer risk to develop a screening plan. The NIH Breast Cancer Surveillance Consortium has published data estimating the risk that a woman with a mammogram negative for cancer will develop breast cancer within the next 12 months (based on her age, breast density, and breast cancer risk—calculated with the BCSC tool).⁸

It reported an increased risk of breast cancer diagnosed within 12 months following a mammogram that was negative for cancer in women with extremely dense breasts and a BCSC 5-year risk of breast cancer of 1.67% or greater and in women with heterogeneously dense breasts and a BCSC 5-year risk of breast cancer of 2.5% or greater.⁸

Using these cutoffs it is estimated that 24% of all women with heterogeneously or extremely dense breasts would be offered supplemental screening with a modality such as ultrasound, and 76% would be guided not to have supplemental screening because their risk of developing breast cancer in the 12 months following their negative mammogram is low.

If this guidance is followed, it would require 694 supplemental ultrasound studies and many biopsies to detect 1 additional breast cancer, significantly increasing overall health care costs.⁸ In many states insurers do not cover supplemental ultrasound imaging of the breasts. In most states insurers require preauthorization for supplemental MRI of the breasts. You need to know the insurance practices in the state to help guide decision making about supplemental imaging. The approach described above is consistent with the American College of Obstetricians and Gynecologists recommendation that women with dense breasts, who are asymptomaticand have no additional risk factors for breast cancer, do not need to be offered supplemental imaging.⁹

Case: Next steps
The BCSC calculator reveals that the 51-year-old woman with a family history of breast cancer and a mammogram showing extremely dense breasts has a 5-year risk of breast cancer of 2.68%. Given that this risk is elevated, this patient could be offered supplemental ultrasound screening and annual breast clinical examination. In addition, she could be further counseled about breast cancer chemoprevention options.¹⁰

Women with a strong family history of breast and/or ovarian cancer also could be referred for genetic counseling and BRCA testing.¹¹ The risk of having a BRCA mutation can be calculated using the BRCAPRO tool.¹²

Most women with dense breast tissue on mammography will never develop breast cancer. Yet the presence of dense breast tissue both increases the risk of breast cancer and decreases the sensitivity of mammography to detect cancer. There are no high-quality data from randomized trials to help guide our recommendations concerning the management of dense breasts identified on mammography. Yet many states have laws that suggest patients ask you to provide advice about breast density.

Patients, clinicians, and health systems vary in their confidence in the clinical value of breast cancer screening programs. Consequently, there is no “right answer” to this vexing problem. The standard of care is to support a range of options tailored to the specific clinical characteristics and needs of each patient. 
 

Case: Patient seeks clarification and next steps on her breast density classification
Your patient, a 51-year-old postmenopausal woman (G0P0) in good health, had an annual screening mammogram that showed no evidence of malignancy. She is white and has a mother with a history of breast cancer. She has never had a breast biopsy. Following the mammogram, she received a letter from the imaging center, stating:

She calls your office and asks, “What should I do next?”

Breasts are composed of fibrous, glandular, and adipose tissue. If the breasts contain a lot of fibrous and glandular tissue, and little adipose tissue, they are considered to be “dense.” Using mammography, the current standard is to report the density of breast tissue using 4 categories:

Dense breast tissue is defined to include the 2 categories heterogeneously dense and extremely dense.

Observational studies have reported that dense breast tissue is associated with an increased risk of breast cancer, and dense breast tissue makes it more difficult to detect breast cancer on mammography. According to data from the Breast Cancer Surveillance Consortium, among women aged 50 or older, the relative risk of breast cancer stratified by the 4 categories of breast density is 0.59, 1.00, 1.46, and 1.77, for almost entirely fatty, scattered fibroglandular densities, heterogeneously dense, and extremely dense, respectively.¹ In one study, the sensitivity of mammography to detect breast cancer was 82% to 88% for women with nondense breasts and 62% to 69% in women with dense breasts.² These data have catalyzed investigators to explore the use of supplemental imaging to enhance cancer detection in women with dense breasts.

The link between breast density and breast cancer risk and reduced sensitivity of mammography also has catalyzed activists and legislators to champion breast density notification laws, which have passed in more than 20 states. These laws require facilities that perform mammography to notify women with dense breasts that this finding is associated with an increased risk of breast cancer and that dense breasts reduce the ability of mammography to detect cancer. In some states, the law mandates that women with dense breasts be offered supplemental ultrasound imaging and that insurers must cover the cost of the ultrasound studies. Many of the laws recommend that the patient discuss the situation with the clinician who ordered the mammogram.

When I first saw the recommendation for patients to contact me about how to manage dense breasts, my initial response was, “Who? Me?” I felt ill equipped to provide any useful advice and suspected that many of my patients knew more than I about this issue.

Based on a review of the evidence, my current clinical recommendation is outlined in the 2 options below, including a low-resource utilization option and a high-resource utilization option. For patients, physicians, and health systems that are concerned that excessive breast cancer screening tests might cause more harm than benefit, the identification of dense breasts on mammogram is unlikely to be a trigger to perform any additional testing. In this situation, the pragmatic low-resource option is most relevant.

Alternatively, for patients and physicians who strongly believe in the value of screening mammography (see “Utilize tomosynthesis digital mammography technology for your patients” below), a reasonable strategy is to recommend that women with dense breasts and an increased risk for breast cancer be offered supplemental imaging.

In this editorial I elaborate these 2 approaches to breast cancer screening in women with dense breasts.
 

A pragmatic, low-resource utilization screening approach for women with dense breasts
There are no published randomized clinical trials that provide high-quality evidence on what to do if dense breasts are identified on mammography.³ Authors of observational studies have evaluated the potential role of supplemental imaging, including ultrasound and magnetic resonance imaging (MRI), in the management of dense breast tissue (see “Supplemental breast cancer screening modalities” below). Supplemental imaging involves complex trade-offs, balancing the potential benefit of identifying occult early breast cancer lesions not identified by mammography with the risk of subjecting many women without cancer to additional testing and unnecessary biopsies.

A pragmatic, low-resource utilization plan for women with dense breasts involves emphasizing that mammography is the best available screening tool and that annual or biennial mammography is the foundation of all current approaches to breast cancer screening. Supplemental imaging is unnecessary with this approach because there is no evidence that it reduces breast cancer mortality. There is, however, substantial evidence that using supplemental imaging for all women with dense breasts will result in little benefit and great costs, including many unnecessary biopsies.^1,4 Women with dense breasts also could consider annual clinical breast examination.

 

A high-resource utilization screening approach
There are no randomized trials to help guide recommendations about how to respond to a finding of dense breasts on mammography. In addition to breast density, many factors influence breast cancer risk, including a patient’s:

Women with both dense breasts and an increased risk of breast cancer may reap the greatest benefit from supplemental imaging, such as ultrasonography. Therefore, a two-step approach can help.

Step 1: Assess breast cancer risk. This can be accomplished using one of many calculators. Three that are commonly used are the:

The BCSC calculator uses age, race/ethnicity, first-degree relatives with breast cancer, a history of a breast biopsy, and breast density to calculate a 5-year risk of developing breast cancer.

The BCRAT tool uses current age, race/ethnicity, age at menarche, age at first live-birth of a child, number of first-degree relatives with breast cancer, a history of breast biopsies, and the identification of atypical hyperplasia to calculate a 5-year risk of breast cancer.

The IBIS model uses many more variables, including a detailed family history to calculate a 10-year and lifetime risk of breast cancer. If a patient has ductal carcinoma in situ, lobular carcinoma in situ, chest irradiation before age 30 years, or known BRCA1 or BRCA2 mutations, she is instructed not to use the risk calculators because they are at very high risk for breast cancer, and they need an individualized intensive plan for monitoring and prevention (see MRI section in “Supplemental breast cancer screening modalities” above).

Step 2: Use breast density and breast cancer risk to develop a screening plan. The NIH Breast Cancer Surveillance Consortium has published data estimating the risk that a woman with a mammogram negative for cancer will develop breast cancer within the next 12 months (based on her age, breast density, and breast cancer risk—calculated with the BCSC tool).⁸

It reported an increased risk of breast cancer diagnosed within 12 months following a mammogram that was negative for cancer in women with extremely dense breasts and a BCSC 5-year risk of breast cancer of 1.67% or greater and in women with heterogeneously dense breasts and a BCSC 5-year risk of breast cancer of 2.5% or greater.⁸

Using these cutoffs it is estimated that 24% of all women with heterogeneously or extremely dense breasts would be offered supplemental screening with a modality such as ultrasound, and 76% would be guided not to have supplemental screening because their risk of developing breast cancer in the 12 months following their negative mammogram is low.

If this guidance is followed, it would require 694 supplemental ultrasound studies and many biopsies to detect 1 additional breast cancer, significantly increasing overall health care costs.⁸ In many states insurers do not cover supplemental ultrasound imaging of the breasts. In most states insurers require preauthorization for supplemental MRI of the breasts. You need to know the insurance practices in the state to help guide decision making about supplemental imaging. The approach described above is consistent with the American College of Obstetricians and Gynecologists recommendation that women with dense breasts, who are asymptomaticand have no additional risk factors for breast cancer, do not need to be offered supplemental imaging.⁹

Case: Next steps
The BCSC calculator reveals that the 51-year-old woman with a family history of breast cancer and a mammogram showing extremely dense breasts has a 5-year risk of breast cancer of 2.68%. Given that this risk is elevated, this patient could be offered supplemental ultrasound screening and annual breast clinical examination. In addition, she could be further counseled about breast cancer chemoprevention options.¹⁰

Women with a strong family history of breast and/or ovarian cancer also could be referred for genetic counseling and BRCA testing.¹¹ The risk of having a BRCA mutation can be calculated using the BRCAPRO tool.¹²

Most women with dense breast tissue on mammography will never develop breast cancer. Yet the presence of dense breast tissue both increases the risk of breast cancer and decreases the sensitivity of mammography to detect cancer. There are no high-quality data from randomized trials to help guide our recommendations concerning the management of dense breasts identified on mammography. Yet many states have laws that suggest patients ask you to provide advice about breast density.

Patients, clinicians, and health systems vary in their confidence in the clinical value of breast cancer screening programs. Consequently, there is no “right answer” to this vexing problem. The standard of care is to support a range of options tailored to the specific clinical characteristics and needs of each patient. 
 

The American Society of Clinical Oncology has issued updated guidelines on using breast tumor biomarker assays to help guide or influence decisions on systemic therapy in women with metastatic breast cancer, which were published online July 20 in the Journal of Clinical Oncology.

The quality of evidence for the recommendations ranges from insufficient to intermediate, and the “strength” of the recommendation was moderate for all of them.

When evaluating metastatic sites, it is important to note that the estrogen receptor (ER), progesterone receptor (PR), and/or human epidermal growth factor receptor 2 (HER2) status may have changed from the primary tumor, and these results could influence treatment. Thus, biopsy should be offered to patients with accessible, newly diagnosed metastases from primary breast cancer, to confirm disease status and test for ER, PR, and HER2 status, wrote Dr. Catherine Van Poznak of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues, as one of the key recommendations (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.1459]).

Patients should be also be told if discordances are detected, and that evidence is lacking to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor.

If supported by the clinical scenario and patient goals for care, the ASCO Panel consensus is to preferentially use the biomarker status from the metastatic site rather than from the primary tumor, to direct therapy.

Decisions for initiating systemic therapy in this patient population should be based on clinical evaluation, judgment, as well as patient preferences. At present, there is no evidence that health outcomes will improve if treatment is initiated based solely on the results of biomarker assays that go beyond ER, PR, and HER2 status.

For patients who are already receiving systemic therapy, decisions for changing drugs or regimens, or discontinuing treatment should be based on clinical evaluation, clinician judgment of disease progression or response, and patient preference and input. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness, they wrote. This recommendation applies for both tissue biomarkers and circulating tumor biomarkers.

The guidelines also recommend that carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 can be used as adjunctive assessments and can contribute to decisions regarding therapy. The data thus far, however, are insufficient to recommend their use alone for monitoring response to treatment. This recommendation, according to the researchers, is based on clinical experience and the informal consensus of the panel, since there are no studies that have been designed to evaluate the clinical utility of the markers.

It is also reasonable for clinicians to not use these markers as adjunctive assessments.

Outside of clinical trials, decisions for systemic therapy should be influenced by ER, PR, and HER2 status, as the clinical usefulness for other biomarkers has not yet been demonstrated. A number of other types of biomarkers are in active development, but there is insufficient evidence at this time showing that their use improves cancer outcomes, the panel said.

Biomarker distribution of ER, PR, and HER2 status may also differ across ethnic and racial backgrounds, and in addition to the biologic variability of these biomarkers, there is also evidence that disparities exist in the frequency of biomarker testing in certain populations.

The American Society of Clinical Oncology has issued updated guidelines on using breast tumor biomarker assays to help guide or influence decisions on systemic therapy in women with metastatic breast cancer, which were published online July 20 in the Journal of Clinical Oncology.

The quality of evidence for the recommendations ranges from insufficient to intermediate, and the “strength” of the recommendation was moderate for all of them.

When evaluating metastatic sites, it is important to note that the estrogen receptor (ER), progesterone receptor (PR), and/or human epidermal growth factor receptor 2 (HER2) status may have changed from the primary tumor, and these results could influence treatment. Thus, biopsy should be offered to patients with accessible, newly diagnosed metastases from primary breast cancer, to confirm disease status and test for ER, PR, and HER2 status, wrote Dr. Catherine Van Poznak of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues, as one of the key recommendations (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.1459]).

Patients should be also be told if discordances are detected, and that evidence is lacking to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor.

If supported by the clinical scenario and patient goals for care, the ASCO Panel consensus is to preferentially use the biomarker status from the metastatic site rather than from the primary tumor, to direct therapy.

Decisions for initiating systemic therapy in this patient population should be based on clinical evaluation, judgment, as well as patient preferences. At present, there is no evidence that health outcomes will improve if treatment is initiated based solely on the results of biomarker assays that go beyond ER, PR, and HER2 status.

For patients who are already receiving systemic therapy, decisions for changing drugs or regimens, or discontinuing treatment should be based on clinical evaluation, clinician judgment of disease progression or response, and patient preference and input. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness, they wrote. This recommendation applies for both tissue biomarkers and circulating tumor biomarkers.

The guidelines also recommend that carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 can be used as adjunctive assessments and can contribute to decisions regarding therapy. The data thus far, however, are insufficient to recommend their use alone for monitoring response to treatment. This recommendation, according to the researchers, is based on clinical experience and the informal consensus of the panel, since there are no studies that have been designed to evaluate the clinical utility of the markers.

It is also reasonable for clinicians to not use these markers as adjunctive assessments.

Outside of clinical trials, decisions for systemic therapy should be influenced by ER, PR, and HER2 status, as the clinical usefulness for other biomarkers has not yet been demonstrated. A number of other types of biomarkers are in active development, but there is insufficient evidence at this time showing that their use improves cancer outcomes, the panel said.

Biomarker distribution of ER, PR, and HER2 status may also differ across ethnic and racial backgrounds, and in addition to the biologic variability of these biomarkers, there is also evidence that disparities exist in the frequency of biomarker testing in certain populations.

The American Society of Clinical Oncology has issued updated guidelines on using breast tumor biomarker assays to help guide or influence decisions on systemic therapy in women with metastatic breast cancer, which were published online July 20 in the Journal of Clinical Oncology.

The quality of evidence for the recommendations ranges from insufficient to intermediate, and the “strength” of the recommendation was moderate for all of them.

When evaluating metastatic sites, it is important to note that the estrogen receptor (ER), progesterone receptor (PR), and/or human epidermal growth factor receptor 2 (HER2) status may have changed from the primary tumor, and these results could influence treatment. Thus, biopsy should be offered to patients with accessible, newly diagnosed metastases from primary breast cancer, to confirm disease status and test for ER, PR, and HER2 status, wrote Dr. Catherine Van Poznak of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues, as one of the key recommendations (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.1459]).

Patients should be also be told if discordances are detected, and that evidence is lacking to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor.

If supported by the clinical scenario and patient goals for care, the ASCO Panel consensus is to preferentially use the biomarker status from the metastatic site rather than from the primary tumor, to direct therapy.

Decisions for initiating systemic therapy in this patient population should be based on clinical evaluation, judgment, as well as patient preferences. At present, there is no evidence that health outcomes will improve if treatment is initiated based solely on the results of biomarker assays that go beyond ER, PR, and HER2 status.

For patients who are already receiving systemic therapy, decisions for changing drugs or regimens, or discontinuing treatment should be based on clinical evaluation, clinician judgment of disease progression or response, and patient preference and input. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness, they wrote. This recommendation applies for both tissue biomarkers and circulating tumor biomarkers.

The guidelines also recommend that carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 can be used as adjunctive assessments and can contribute to decisions regarding therapy. The data thus far, however, are insufficient to recommend their use alone for monitoring response to treatment. This recommendation, according to the researchers, is based on clinical experience and the informal consensus of the panel, since there are no studies that have been designed to evaluate the clinical utility of the markers.

It is also reasonable for clinicians to not use these markers as adjunctive assessments.

Outside of clinical trials, decisions for systemic therapy should be influenced by ER, PR, and HER2 status, as the clinical usefulness for other biomarkers has not yet been demonstrated. A number of other types of biomarkers are in active development, but there is insufficient evidence at this time showing that their use improves cancer outcomes, the panel said.

Biomarker distribution of ER, PR, and HER2 status may also differ across ethnic and racial backgrounds, and in addition to the biologic variability of these biomarkers, there is also evidence that disparities exist in the frequency of biomarker testing in certain populations.