Breast Cancer

SAN DIEGO – A Rapid Quality Reporting System significantly improved oncologists’ adherence to five measures of quality treatment for patients with breast and colon cancer during beta testing involving 64,129 patients at 64 cancer centers.

The system, developed by the American College of Surgeons’ Commission on Cancer, provides next-business-day feedback when centers submit data. Compliance rates climbed as high as 90% by the end of a 5-year period, according to researchers.

Erica J. McNamara and her associates reported the following gains at a symposium on quality care sponsored by the American Society of Clinical Oncology (ASCO):

• The proportion of patients receiving hormone therapy for hormone receptor–positive breast cancer increased from 47% in 2006 to 85% in 2011.

• Treatment with radiation following breast conserving surgery increased from 69% of patients to 90%.

• Use of multi-adjuvant chemotherapy for hormone receptor–negative breast cancer increased from 72% of patients to 90%,

• Treatment with adjuvant chemotherapy for lymph node–positive colon cancer increased from 68% to 86%.

• The proportion of patients with resected colon cancer who had at least 12 regional lymph nodes removed for pathological examination improved from 70% to 90%,

The study gathered data from the National Cancer Database in 2006-2007 for 18,151 patients with breast cancer and 6,369 patients with colon cancer and compared it with data reported to the Rapid Quality Reporting System (RQRS) in 2008-2011 for 31,590 patients with breast cancer and 11,338 patients with colon cancer.

The system monitors the five quality measures using reporting procedures similar to those that hospitals already use to submit patient data to cancer registries. Traditional registries generally report a hospital’s rate of performing quality measures 2 years after data submission, however, while the RQRS allows cancer programs to submit data whenever they want and sends feedback by the next business day, said Ms. McNamara, a quality improvement information analyst for the American College of Surgeons, Chicago.

With as little as a surgical or pathological report, cancer programs can submit a case to the RQRS to get alerts when quality care is not being provided. "What this does is it changes it from looking at retrospective cases to cases that are currently within their first course of therapy," she said in a press conference before the meeting.

Programs participating in the beta-test generally submitted data monthly, and new participants in the RQRS are required to submit data at least quarterly. The RQRS analyzes the data and returns a report in a variety of image formats, such as a year-to-date "dashboard" showing the program’s compliance rates for individual quality measures, and a list of every case submitted and whether the quality measures were applicable to the case or not, or if more information is needed.

The report also includes color-coded "case alerts" with the colors changing to orange and then red as a patient gets closer to the end of the first course of therapy with either no documentation of adjuvant therapy or no documentation that treatment decision has been made to not provide adjuvant therapy. Participants must log in to a password-protected site to view details of the case.

"For each of the adjuvant therapy measures, there’s a specific amount of time that each patient has to receive their adjuvant therapy," Ms. McNamara said. "We find that after about 6-9 months of using RQRS, about a third of programs tell us that they have seen RQRS prevent patients from slipping through the cracks or not receiving timely adjuvant care."

Breakdowns of the data by race, age, and type of insurance showed that quality care significantly improved in all subgroups. Disparities in quality adherence rates between patients of different races, ages, or insurance status were minimized or eliminated with use of the RQRS.

Two factors appeared to produce these improvements. Use of the RQRS improved the coordination of care and led to more complete reporting of adjuvant therapy data, she said.

More than 400 cancer programs now voluntarily use the RQRS. The American College of Surgeons is working on expanding the RQRS to include other measures of quality care for breast cancer and for lung, stomach, and esophageal cancers.

Ms. McNamara reported having no financial disclosures.

SAN DIEGO – A Rapid Quality Reporting System significantly improved oncologists’ adherence to five measures of quality treatment for patients with breast and colon cancer during beta testing involving 64,129 patients at 64 cancer centers.

The system, developed by the American College of Surgeons’ Commission on Cancer, provides next-business-day feedback when centers submit data. Compliance rates climbed as high as 90% by the end of a 5-year period, according to researchers.

Erica J. McNamara and her associates reported the following gains at a symposium on quality care sponsored by the American Society of Clinical Oncology (ASCO):

• The proportion of patients receiving hormone therapy for hormone receptor–positive breast cancer increased from 47% in 2006 to 85% in 2011.

• Treatment with radiation following breast conserving surgery increased from 69% of patients to 90%.

• Use of multi-adjuvant chemotherapy for hormone receptor–negative breast cancer increased from 72% of patients to 90%,

• Treatment with adjuvant chemotherapy for lymph node–positive colon cancer increased from 68% to 86%.

• The proportion of patients with resected colon cancer who had at least 12 regional lymph nodes removed for pathological examination improved from 70% to 90%,

The study gathered data from the National Cancer Database in 2006-2007 for 18,151 patients with breast cancer and 6,369 patients with colon cancer and compared it with data reported to the Rapid Quality Reporting System (RQRS) in 2008-2011 for 31,590 patients with breast cancer and 11,338 patients with colon cancer.

The system monitors the five quality measures using reporting procedures similar to those that hospitals already use to submit patient data to cancer registries. Traditional registries generally report a hospital’s rate of performing quality measures 2 years after data submission, however, while the RQRS allows cancer programs to submit data whenever they want and sends feedback by the next business day, said Ms. McNamara, a quality improvement information analyst for the American College of Surgeons, Chicago.

With as little as a surgical or pathological report, cancer programs can submit a case to the RQRS to get alerts when quality care is not being provided. "What this does is it changes it from looking at retrospective cases to cases that are currently within their first course of therapy," she said in a press conference before the meeting.

Programs participating in the beta-test generally submitted data monthly, and new participants in the RQRS are required to submit data at least quarterly. The RQRS analyzes the data and returns a report in a variety of image formats, such as a year-to-date "dashboard" showing the program’s compliance rates for individual quality measures, and a list of every case submitted and whether the quality measures were applicable to the case or not, or if more information is needed.

The report also includes color-coded "case alerts" with the colors changing to orange and then red as a patient gets closer to the end of the first course of therapy with either no documentation of adjuvant therapy or no documentation that treatment decision has been made to not provide adjuvant therapy. Participants must log in to a password-protected site to view details of the case.

"For each of the adjuvant therapy measures, there’s a specific amount of time that each patient has to receive their adjuvant therapy," Ms. McNamara said. "We find that after about 6-9 months of using RQRS, about a third of programs tell us that they have seen RQRS prevent patients from slipping through the cracks or not receiving timely adjuvant care."

Breakdowns of the data by race, age, and type of insurance showed that quality care significantly improved in all subgroups. Disparities in quality adherence rates between patients of different races, ages, or insurance status were minimized or eliminated with use of the RQRS.

Two factors appeared to produce these improvements. Use of the RQRS improved the coordination of care and led to more complete reporting of adjuvant therapy data, she said.

More than 400 cancer programs now voluntarily use the RQRS. The American College of Surgeons is working on expanding the RQRS to include other measures of quality care for breast cancer and for lung, stomach, and esophageal cancers.

Ms. McNamara reported having no financial disclosures.

SAN DIEGO – A Rapid Quality Reporting System significantly improved oncologists’ adherence to five measures of quality treatment for patients with breast and colon cancer during beta testing involving 64,129 patients at 64 cancer centers.

The system, developed by the American College of Surgeons’ Commission on Cancer, provides next-business-day feedback when centers submit data. Compliance rates climbed as high as 90% by the end of a 5-year period, according to researchers.

Erica J. McNamara and her associates reported the following gains at a symposium on quality care sponsored by the American Society of Clinical Oncology (ASCO):

• The proportion of patients receiving hormone therapy for hormone receptor–positive breast cancer increased from 47% in 2006 to 85% in 2011.

• Treatment with radiation following breast conserving surgery increased from 69% of patients to 90%.

• Use of multi-adjuvant chemotherapy for hormone receptor–negative breast cancer increased from 72% of patients to 90%,

• Treatment with adjuvant chemotherapy for lymph node–positive colon cancer increased from 68% to 86%.

• The proportion of patients with resected colon cancer who had at least 12 regional lymph nodes removed for pathological examination improved from 70% to 90%,

The study gathered data from the National Cancer Database in 2006-2007 for 18,151 patients with breast cancer and 6,369 patients with colon cancer and compared it with data reported to the Rapid Quality Reporting System (RQRS) in 2008-2011 for 31,590 patients with breast cancer and 11,338 patients with colon cancer.

The system monitors the five quality measures using reporting procedures similar to those that hospitals already use to submit patient data to cancer registries. Traditional registries generally report a hospital’s rate of performing quality measures 2 years after data submission, however, while the RQRS allows cancer programs to submit data whenever they want and sends feedback by the next business day, said Ms. McNamara, a quality improvement information analyst for the American College of Surgeons, Chicago.

With as little as a surgical or pathological report, cancer programs can submit a case to the RQRS to get alerts when quality care is not being provided. "What this does is it changes it from looking at retrospective cases to cases that are currently within their first course of therapy," she said in a press conference before the meeting.

Programs participating in the beta-test generally submitted data monthly, and new participants in the RQRS are required to submit data at least quarterly. The RQRS analyzes the data and returns a report in a variety of image formats, such as a year-to-date "dashboard" showing the program’s compliance rates for individual quality measures, and a list of every case submitted and whether the quality measures were applicable to the case or not, or if more information is needed.

The report also includes color-coded "case alerts" with the colors changing to orange and then red as a patient gets closer to the end of the first course of therapy with either no documentation of adjuvant therapy or no documentation that treatment decision has been made to not provide adjuvant therapy. Participants must log in to a password-protected site to view details of the case.

"For each of the adjuvant therapy measures, there’s a specific amount of time that each patient has to receive their adjuvant therapy," Ms. McNamara said. "We find that after about 6-9 months of using RQRS, about a third of programs tell us that they have seen RQRS prevent patients from slipping through the cracks or not receiving timely adjuvant care."

Breakdowns of the data by race, age, and type of insurance showed that quality care significantly improved in all subgroups. Disparities in quality adherence rates between patients of different races, ages, or insurance status were minimized or eliminated with use of the RQRS.

Two factors appeared to produce these improvements. Use of the RQRS improved the coordination of care and led to more complete reporting of adjuvant therapy data, she said.

More than 400 cancer programs now voluntarily use the RQRS. The American College of Surgeons is working on expanding the RQRS to include other measures of quality care for breast cancer and for lung, stomach, and esophageal cancers.

Ms. McNamara reported having no financial disclosures.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium, discusses research that will be presented at the 2012 meeting – and how it might affect clinical practice.

Dr. Osborne is professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Once again, thousands of oncologists are heading to San Antonio and the annual breast cancer symposium. What makes this meeting so important to the breast cancer community?

DR. OSBORNE: Well, it’s the largest annual meeting devoted to presentation of new research findings in breast cancer research, both clinical trials and basic and translational research. And it’s in its 33rd year, I think now, so it’s become the standard for people to attend to find out the latest research results in breast cancer.

The buildup to the 2012 symposium has been relatively quiet compared with the excitement last year. Can you give us a preview of some of the phase III trials that will be reporting results in San Antonio?

DR. OSBORNE: I didn’t think of it as being more quiet, because to me I think it’s more exciting. There are several trials that I think are going to have a big impact.

One is the so-called ATLAS trial from the U.K., which looked at the question of duration of tamoxifen adjuvant therapy. Two prior studies, although smaller ones, suggested that prolonging tamoxifen beyond 5 years to, say, 10 years was no more effective than stopping at 5 years. This trial is a much larger trial and looks to extending tamoxifen to more than 5 years, and it will be interesting to see the results, to see whether it confirms the other two trials or whether it provides a different result that winds up changing practice.

In addition, in the HER2 setting there are two extremely important studies coming out that will probably be practice changing or practice confirming, maybe. One is the HERA trial in HER2positive patients, where patients were randomized between 1 year and 2 years of trastuzumab after their chemotherapy, and depending on that result we might wind up either continuing to stop trastuzumab at 1 year, which is the current recommendation, or extending it to 2 years.

At then the same time there is a trial from France, the PHARE trial, which looked at 6 months of trastuzumab versus 1 year. So I think these two trials – one looking at a shorter duration and one looking at a longer duration – will help to set the standard of the duration of trastuzumab therapy in patients with HER2-positive breast cancer.

I think both of those are going to be extremely important studies.

What are some of the other pressing topics? Will we be hearing about triple-negative breast cancer?

DR. OSBORNE: There is a session that contains several interesting papers on triple-negative breast cancer, as we begin to define the pathways that are responsible for its development and progression. And then there is another study that’ll be coming out that looks at another inhibitor in combination with an aromatase inhibitor in estrogenpositive type breast cancer. It looks at an inhibitor of cyclin-dependent kinase 4/6 along with an aromatase inhibitor, and we’ll see if it provides similar data to the BOLERO-2 trial using a slightly different drug and a different target. But that should be very interesting as well, as we begin to learn what other pathways besides the estrogen receptor can contribute to breast cancer growth in patients with ER-positive metastatic disease.

Anything about biomarkers?

DR. OSBORNE: There will be some trials looking at biomarkers in patients on the NEOSPHERE trial – that was a neoadjuvant trial of the combination of trastuzumab and pertuzumab, which might tell us something about a resistance mechanism or sensitivity biomarkers – and then in the CLEOPATRA study there will be some biomarker studies relating outcome to the biomarkers. That should be of interest as well.

There always are some biomarker studies that will be presented, and those are two that come to mind that will be particularly interesting.

Thank you Dr. Osborne. Our reporting team will be in San Antonio for this important meeting, so I think we will see you there.

DR. OSBORNE: Thank you.

Thank you very much.

Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium, discusses research that will be presented at the 2012 meeting – and how it might affect clinical practice.

Dr. Osborne is professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Once again, thousands of oncologists are heading to San Antonio and the annual breast cancer symposium. What makes this meeting so important to the breast cancer community?

DR. OSBORNE: Well, it’s the largest annual meeting devoted to presentation of new research findings in breast cancer research, both clinical trials and basic and translational research. And it’s in its 33rd year, I think now, so it’s become the standard for people to attend to find out the latest research results in breast cancer.

The buildup to the 2012 symposium has been relatively quiet compared with the excitement last year. Can you give us a preview of some of the phase III trials that will be reporting results in San Antonio?

DR. OSBORNE: I didn’t think of it as being more quiet, because to me I think it’s more exciting. There are several trials that I think are going to have a big impact.

One is the so-called ATLAS trial from the U.K., which looked at the question of duration of tamoxifen adjuvant therapy. Two prior studies, although smaller ones, suggested that prolonging tamoxifen beyond 5 years to, say, 10 years was no more effective than stopping at 5 years. This trial is a much larger trial and looks to extending tamoxifen to more than 5 years, and it will be interesting to see the results, to see whether it confirms the other two trials or whether it provides a different result that winds up changing practice.

In addition, in the HER2 setting there are two extremely important studies coming out that will probably be practice changing or practice confirming, maybe. One is the HERA trial in HER2positive patients, where patients were randomized between 1 year and 2 years of trastuzumab after their chemotherapy, and depending on that result we might wind up either continuing to stop trastuzumab at 1 year, which is the current recommendation, or extending it to 2 years.

At then the same time there is a trial from France, the PHARE trial, which looked at 6 months of trastuzumab versus 1 year. So I think these two trials – one looking at a shorter duration and one looking at a longer duration – will help to set the standard of the duration of trastuzumab therapy in patients with HER2-positive breast cancer.

I think both of those are going to be extremely important studies.

What are some of the other pressing topics? Will we be hearing about triple-negative breast cancer?

DR. OSBORNE: There is a session that contains several interesting papers on triple-negative breast cancer, as we begin to define the pathways that are responsible for its development and progression. And then there is another study that’ll be coming out that looks at another inhibitor in combination with an aromatase inhibitor in estrogenpositive type breast cancer. It looks at an inhibitor of cyclin-dependent kinase 4/6 along with an aromatase inhibitor, and we’ll see if it provides similar data to the BOLERO-2 trial using a slightly different drug and a different target. But that should be very interesting as well, as we begin to learn what other pathways besides the estrogen receptor can contribute to breast cancer growth in patients with ER-positive metastatic disease.

Anything about biomarkers?

DR. OSBORNE: There will be some trials looking at biomarkers in patients on the NEOSPHERE trial – that was a neoadjuvant trial of the combination of trastuzumab and pertuzumab, which might tell us something about a resistance mechanism or sensitivity biomarkers – and then in the CLEOPATRA study there will be some biomarker studies relating outcome to the biomarkers. That should be of interest as well.

There always are some biomarker studies that will be presented, and those are two that come to mind that will be particularly interesting.

Thank you Dr. Osborne. Our reporting team will be in San Antonio for this important meeting, so I think we will see you there.

DR. OSBORNE: Thank you.

Thank you very much.

Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium, discusses research that will be presented at the 2012 meeting – and how it might affect clinical practice.

Dr. Osborne is professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

Once again, thousands of oncologists are heading to San Antonio and the annual breast cancer symposium. What makes this meeting so important to the breast cancer community?

DR. OSBORNE: Well, it’s the largest annual meeting devoted to presentation of new research findings in breast cancer research, both clinical trials and basic and translational research. And it’s in its 33rd year, I think now, so it’s become the standard for people to attend to find out the latest research results in breast cancer.

The buildup to the 2012 symposium has been relatively quiet compared with the excitement last year. Can you give us a preview of some of the phase III trials that will be reporting results in San Antonio?

DR. OSBORNE: I didn’t think of it as being more quiet, because to me I think it’s more exciting. There are several trials that I think are going to have a big impact.

One is the so-called ATLAS trial from the U.K., which looked at the question of duration of tamoxifen adjuvant therapy. Two prior studies, although smaller ones, suggested that prolonging tamoxifen beyond 5 years to, say, 10 years was no more effective than stopping at 5 years. This trial is a much larger trial and looks to extending tamoxifen to more than 5 years, and it will be interesting to see the results, to see whether it confirms the other two trials or whether it provides a different result that winds up changing practice.

In addition, in the HER2 setting there are two extremely important studies coming out that will probably be practice changing or practice confirming, maybe. One is the HERA trial in HER2positive patients, where patients were randomized between 1 year and 2 years of trastuzumab after their chemotherapy, and depending on that result we might wind up either continuing to stop trastuzumab at 1 year, which is the current recommendation, or extending it to 2 years.

At then the same time there is a trial from France, the PHARE trial, which looked at 6 months of trastuzumab versus 1 year. So I think these two trials – one looking at a shorter duration and one looking at a longer duration – will help to set the standard of the duration of trastuzumab therapy in patients with HER2-positive breast cancer.

I think both of those are going to be extremely important studies.

What are some of the other pressing topics? Will we be hearing about triple-negative breast cancer?

DR. OSBORNE: There is a session that contains several interesting papers on triple-negative breast cancer, as we begin to define the pathways that are responsible for its development and progression. And then there is another study that’ll be coming out that looks at another inhibitor in combination with an aromatase inhibitor in estrogenpositive type breast cancer. It looks at an inhibitor of cyclin-dependent kinase 4/6 along with an aromatase inhibitor, and we’ll see if it provides similar data to the BOLERO-2 trial using a slightly different drug and a different target. But that should be very interesting as well, as we begin to learn what other pathways besides the estrogen receptor can contribute to breast cancer growth in patients with ER-positive metastatic disease.

Anything about biomarkers?

DR. OSBORNE: There will be some trials looking at biomarkers in patients on the NEOSPHERE trial – that was a neoadjuvant trial of the combination of trastuzumab and pertuzumab, which might tell us something about a resistance mechanism or sensitivity biomarkers – and then in the CLEOPATRA study there will be some biomarker studies relating outcome to the biomarkers. That should be of interest as well.

There always are some biomarker studies that will be presented, and those are two that come to mind that will be particularly interesting.

Thank you Dr. Osborne. Our reporting team will be in San Antonio for this important meeting, so I think we will see you there.

DR. OSBORNE: Thank you.

Thank you very much.

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

Among breast cancer patients, women who worry the most that localized cancer in one breast will spread to the other breast are twice as likely to choose a prophylactic double mastectomy – even though most of them have no clinical indication for the procedure, a study of 1,446 patients showed.

Approximately 80% of the 107 women in the study who chose prophylactic double mastectomy had a very low risk for contralateral disease, Sarah T. Hawley, Ph.D., said in a press conference sponsored by the American Society of Clinical Oncology (ASCO).

She is slated to present the results at a symposium on quality care sponsored by the American Society of Clinical Oncology, taking place Nov. 30 to Dec. 1 in San Diego.

Many women undergo unnecessary surgery out of ungrounded fear that cancer in one breast will lead to cancer in the other, said Dr. Hawley of the division of general medicine at the University of Michigan, Ann Arbor.

Women’s worry about cancer spreading from one breast to the other "really shouldn’t be a reason to get that procedure," she said.

Contralateral prophylactic mastectomy can be considered if a patient is positive for BRCA1 or BRCA2 mutations or has a family history of breast or ovarian cancer in two or more first-degree relatives, according to Society of Surgical Oncology guidelines.

"Despite the small number of women who meet these criteria, rates of contralateral prophylactic mastectomy have been increasing in recent years," Dr. Hawley noted.

Those traditional indications still were powerful drivers in the study – a positive genetic test increased the odds of contralateral prophylactic mastectomy 10-fold, and a family history increased the odds 5-fold.

The doubling in odds of contralateral prophylactic mastectomy in women with a high level of worry (compared with low worry level) is notable because the prophylactic surgery has not been known to reduce the risk of recurrence when those indications are not present, as was the case with the majority of women who chose the procedure in the study.

Among women who chose contralateral prophylactic mastectomy, 90% reported high levels of worry, compared with 80% of the 564 women who underwent single-breast mastectomy, a statistically significant difference, Dr. Hawley reported.

She and her associates studied 1,446 newly diagnosed breast cancer patients who completed two surveys 4 years apart, had not had a recurrence during that time, and had complete data on genetic testing and family history. Contralateral prophylactic mastectomy was considered by 35% of the whole cohort and chosen by 7%. Among women who underwent mastectomy of the cancerous breast, 53% considered contralateral prophylactic mastectomy and 19% underwent the procedure.

When women were considering any mastectomy vs. breast conservation surgery, family history and genetic test results did not significantly affect the odds that they would choose any mastectomy, but their level of worry did. High levels of worry significantly increased the odds of mastectomy by 69% in a subanalysis that controlled for the effects of age, race or ethnicity, education, and cancer stage.

A separate subanalysis found that both clinical indications and worry affected the likelihood of contralateral prophylactic mastectomy compared with unilateral mastectomy. The odds of having the prophylactic surgery increased more than 4-fold with a family history of at least two primary relatives with breast cancer, more than 10-fold with a positive genetic test, and more than 2-fold with a high degree of worry in the multivariate analysis, Dr. Hawley said.

Compared with previous studies on why women are getting contralateral prophylactic mastectomy, the current study is larger; is population-based; contains racial and ethnic samples; and includes data on patient attitudes, genetic testing, and type of family history (not just any family history), she said.

Dr. Jyoti D. Patel, moderator of the press conference, said the findings suggest that "we, as physicians, may not be adequately educating our patients about the risk for recurrent disease."

In general, women with localized breast cancer in one breast have less than a 1% chance of developing a new cancer in the unaffected breast and an 8% chance of recurrence in the affected breast or a nearby lymph node. The risk for developing a new cancer in the contralateral breast rises to approximately 10%-15% if the patient has a history of breast or ovarian cancer in two or more primary relatives, with a similar or slightly greater increased risk from a positive genetic mutation, Dr. Patel estimated. Having both clinical risk factors confers a 10- to 20-fold increase in risk.

Unfortunately, many women overestimate their risk of developing breast cancer in the contralateral breast and undergo unnecessary surgery, she commented. This study suggests that physicians re-examine how they communicate with their patients regarding the decision to undergo prophylactic mastectomy.

"Many women fear recurrence, and they also fear surveillance. They worry about, if they’re 35 years old, what a lifetime of screening for the contralateral breast might look like if they end up getting multiple biopsies. So how we put that in perspective for our young population will become vitally important," said Dr. Patell, a thoracic oncologist at Northwestern University in Chicago and a member of ASCO’s Cancer Communications Committee.

Dr. Hawley reported having no financial disclosures.

Among breast cancer patients, women who worry the most that localized cancer in one breast will spread to the other breast are twice as likely to choose a prophylactic double mastectomy – even though most of them have no clinical indication for the procedure, a study of 1,446 patients showed.

Approximately 80% of the 107 women in the study who chose prophylactic double mastectomy had a very low risk for contralateral disease, Sarah T. Hawley, Ph.D., said in a press conference sponsored by the American Society of Clinical Oncology (ASCO).

She is slated to present the results at a symposium on quality care sponsored by the American Society of Clinical Oncology, taking place Nov. 30 to Dec. 1 in San Diego.

Many women undergo unnecessary surgery out of ungrounded fear that cancer in one breast will lead to cancer in the other, said Dr. Hawley of the division of general medicine at the University of Michigan, Ann Arbor.

Women’s worry about cancer spreading from one breast to the other "really shouldn’t be a reason to get that procedure," she said.

Contralateral prophylactic mastectomy can be considered if a patient is positive for BRCA1 or BRCA2 mutations or has a family history of breast or ovarian cancer in two or more first-degree relatives, according to Society of Surgical Oncology guidelines.

"Despite the small number of women who meet these criteria, rates of contralateral prophylactic mastectomy have been increasing in recent years," Dr. Hawley noted.

Those traditional indications still were powerful drivers in the study – a positive genetic test increased the odds of contralateral prophylactic mastectomy 10-fold, and a family history increased the odds 5-fold.

The doubling in odds of contralateral prophylactic mastectomy in women with a high level of worry (compared with low worry level) is notable because the prophylactic surgery has not been known to reduce the risk of recurrence when those indications are not present, as was the case with the majority of women who chose the procedure in the study.

Among women who chose contralateral prophylactic mastectomy, 90% reported high levels of worry, compared with 80% of the 564 women who underwent single-breast mastectomy, a statistically significant difference, Dr. Hawley reported.

She and her associates studied 1,446 newly diagnosed breast cancer patients who completed two surveys 4 years apart, had not had a recurrence during that time, and had complete data on genetic testing and family history. Contralateral prophylactic mastectomy was considered by 35% of the whole cohort and chosen by 7%. Among women who underwent mastectomy of the cancerous breast, 53% considered contralateral prophylactic mastectomy and 19% underwent the procedure.

When women were considering any mastectomy vs. breast conservation surgery, family history and genetic test results did not significantly affect the odds that they would choose any mastectomy, but their level of worry did. High levels of worry significantly increased the odds of mastectomy by 69% in a subanalysis that controlled for the effects of age, race or ethnicity, education, and cancer stage.

A separate subanalysis found that both clinical indications and worry affected the likelihood of contralateral prophylactic mastectomy compared with unilateral mastectomy. The odds of having the prophylactic surgery increased more than 4-fold with a family history of at least two primary relatives with breast cancer, more than 10-fold with a positive genetic test, and more than 2-fold with a high degree of worry in the multivariate analysis, Dr. Hawley said.

Compared with previous studies on why women are getting contralateral prophylactic mastectomy, the current study is larger; is population-based; contains racial and ethnic samples; and includes data on patient attitudes, genetic testing, and type of family history (not just any family history), she said.

Dr. Jyoti D. Patel, moderator of the press conference, said the findings suggest that "we, as physicians, may not be adequately educating our patients about the risk for recurrent disease."

In general, women with localized breast cancer in one breast have less than a 1% chance of developing a new cancer in the unaffected breast and an 8% chance of recurrence in the affected breast or a nearby lymph node. The risk for developing a new cancer in the contralateral breast rises to approximately 10%-15% if the patient has a history of breast or ovarian cancer in two or more primary relatives, with a similar or slightly greater increased risk from a positive genetic mutation, Dr. Patel estimated. Having both clinical risk factors confers a 10- to 20-fold increase in risk.

Unfortunately, many women overestimate their risk of developing breast cancer in the contralateral breast and undergo unnecessary surgery, she commented. This study suggests that physicians re-examine how they communicate with their patients regarding the decision to undergo prophylactic mastectomy.

"Many women fear recurrence, and they also fear surveillance. They worry about, if they’re 35 years old, what a lifetime of screening for the contralateral breast might look like if they end up getting multiple biopsies. So how we put that in perspective for our young population will become vitally important," said Dr. Patell, a thoracic oncologist at Northwestern University in Chicago and a member of ASCO’s Cancer Communications Committee.

Dr. Hawley reported having no financial disclosures.

Among breast cancer patients, women who worry the most that localized cancer in one breast will spread to the other breast are twice as likely to choose a prophylactic double mastectomy – even though most of them have no clinical indication for the procedure, a study of 1,446 patients showed.

Approximately 80% of the 107 women in the study who chose prophylactic double mastectomy had a very low risk for contralateral disease, Sarah T. Hawley, Ph.D., said in a press conference sponsored by the American Society of Clinical Oncology (ASCO).

She is slated to present the results at a symposium on quality care sponsored by the American Society of Clinical Oncology, taking place Nov. 30 to Dec. 1 in San Diego.

Many women undergo unnecessary surgery out of ungrounded fear that cancer in one breast will lead to cancer in the other, said Dr. Hawley of the division of general medicine at the University of Michigan, Ann Arbor.

Women’s worry about cancer spreading from one breast to the other "really shouldn’t be a reason to get that procedure," she said.

Contralateral prophylactic mastectomy can be considered if a patient is positive for BRCA1 or BRCA2 mutations or has a family history of breast or ovarian cancer in two or more first-degree relatives, according to Society of Surgical Oncology guidelines.

"Despite the small number of women who meet these criteria, rates of contralateral prophylactic mastectomy have been increasing in recent years," Dr. Hawley noted.

Those traditional indications still were powerful drivers in the study – a positive genetic test increased the odds of contralateral prophylactic mastectomy 10-fold, and a family history increased the odds 5-fold.

The doubling in odds of contralateral prophylactic mastectomy in women with a high level of worry (compared with low worry level) is notable because the prophylactic surgery has not been known to reduce the risk of recurrence when those indications are not present, as was the case with the majority of women who chose the procedure in the study.

Among women who chose contralateral prophylactic mastectomy, 90% reported high levels of worry, compared with 80% of the 564 women who underwent single-breast mastectomy, a statistically significant difference, Dr. Hawley reported.

She and her associates studied 1,446 newly diagnosed breast cancer patients who completed two surveys 4 years apart, had not had a recurrence during that time, and had complete data on genetic testing and family history. Contralateral prophylactic mastectomy was considered by 35% of the whole cohort and chosen by 7%. Among women who underwent mastectomy of the cancerous breast, 53% considered contralateral prophylactic mastectomy and 19% underwent the procedure.

When women were considering any mastectomy vs. breast conservation surgery, family history and genetic test results did not significantly affect the odds that they would choose any mastectomy, but their level of worry did. High levels of worry significantly increased the odds of mastectomy by 69% in a subanalysis that controlled for the effects of age, race or ethnicity, education, and cancer stage.

A separate subanalysis found that both clinical indications and worry affected the likelihood of contralateral prophylactic mastectomy compared with unilateral mastectomy. The odds of having the prophylactic surgery increased more than 4-fold with a family history of at least two primary relatives with breast cancer, more than 10-fold with a positive genetic test, and more than 2-fold with a high degree of worry in the multivariate analysis, Dr. Hawley said.

Compared with previous studies on why women are getting contralateral prophylactic mastectomy, the current study is larger; is population-based; contains racial and ethnic samples; and includes data on patient attitudes, genetic testing, and type of family history (not just any family history), she said.

Dr. Jyoti D. Patel, moderator of the press conference, said the findings suggest that "we, as physicians, may not be adequately educating our patients about the risk for recurrent disease."

In general, women with localized breast cancer in one breast have less than a 1% chance of developing a new cancer in the unaffected breast and an 8% chance of recurrence in the affected breast or a nearby lymph node. The risk for developing a new cancer in the contralateral breast rises to approximately 10%-15% if the patient has a history of breast or ovarian cancer in two or more primary relatives, with a similar or slightly greater increased risk from a positive genetic mutation, Dr. Patel estimated. Having both clinical risk factors confers a 10- to 20-fold increase in risk.

Unfortunately, many women overestimate their risk of developing breast cancer in the contralateral breast and undergo unnecessary surgery, she commented. This study suggests that physicians re-examine how they communicate with their patients regarding the decision to undergo prophylactic mastectomy.

"Many women fear recurrence, and they also fear surveillance. They worry about, if they’re 35 years old, what a lifetime of screening for the contralateral breast might look like if they end up getting multiple biopsies. So how we put that in perspective for our young population will become vitally important," said Dr. Patell, a thoracic oncologist at Northwestern University in Chicago and a member of ASCO’s Cancer Communications Committee.

Dr. Hawley reported having no financial disclosures.

The New England Journal of Medicine study contends that more than 1 million women were overdiagnosed with breast cancer – and overtreated – as a result of screening mammography. How does this affect your thinking on screening mammography – and will it affect practice?

Not Convinced That Change is Called For

Charles B. Hammond, M.D.,

Professor and Chairman Emeritus in the Department of Obstetrics and Gynecology

Duke University

Durham, N.C.

Editorial Advisory Board, Ob.Gyn. News

The NEJM findings do not convince me to change my approach to breast cancer screening. If a woman has no family history or findings on physical examination, I recommend a baseline mammogram at age 35 years, with no more until age 40 years, and then a mammogram every year thereafter. If a woman has a significant family history, I try to get markers on that individual, then repeat mammograms from 35 years on. If the markers are positive, I use other studies with more sensitivity, such as computed tomography, etc.

You can see I am aggressive about this subject. Even with the false positives and surgery involved, this is what I recommend to my patients. I realize this is costly in dollars and in terms of increased concerns for the patients, and that there are low but real risks of surgical complications. I also still advise self breast exams and physician exams yearly, or whenever patients have concerns from their breast self exams. I know mammograms are not perfect and there are false positives and false negatives, but that is what I do and will do until other, better tests are developed.

Follow the Guidelines in Place

Sandra M. Swain, M.D.

President, American Society of Clinical Oncology

Medical Director, Washington Cancer Institute, Washington Hospital Center

Professor of Medicine

Georgetown University

Washington

Women should continue to follow the guidelines that are in place which recommend regular screening. Extensive evidence shows regular screening is important for some women, but more research into the biology of the tumors will be critical to establish which women will benefit most.

Consider the Good and the Bad – and Keep Questioning the Status Quo

Charles Loprinzi, M.D.

Regis Professor of Breast Cancer Research

Division of Medical Oncology

Mayo Clinic

Rochester, Minn.

Associate editor, The Oncology Report

Screening for any cancer (including mammography for breast cancer) can result in good and bad. The good is fairly well appreciated – that is, that a cancer is detected at an early stage, allowing the patient to be treated and cured, when the natural history of the cancer would have been to cause morbidity and/or kill the patient.

However, several bad things can occur with screening, including:

• A false positive result. This can lead to increased concern, testing, and treatment (e.g., bilateral prophylactic mastectomies) for nondisease.

• A false negative result. This may be detrimental in that a patient with a recent normal screening test may ignore a subsequent lump or symptom (that may actually represent a cancer), as she was falsely reassured by the negative test result.

• Finding a cancer that would never have caused morbidity or mortality.

• Finding a cancer that would cause morbidity or mortality but still does (on the same timelines) despite early treatment, thus subjecting the patient to earlier treatment morbidities.

• Diagnosing a cancer and initiating treatment that leads to subsequent major morbidity or mortality, earlier than the cancer would have naturally caused (e.g., a treatment-related leukemia).

• A diagnosis of cancer that leads to treatment (e.g., surgery, radiation therapy, and chemotherapy), with a later determination (by expert pathology review) that the cancer diagnosis was wrong.

For all of these reasons, we need to continue to study and question what we are doing with cancer screening, despite the social and political backlashes that sometimes occur with reports that question the status quo.

The "Ostrich Approach" Makes Little Sense

Howard A. Burris III, M.D.

Chief Medical Officer

Executive Director, Drug Development Program

Sarah Cannon Research Institute

Nashville, Tenn.

Editor-in-chief, The Oncology Report

I agree with Dr. Loprinzi’s thoughtful and well-articulated arguments. Following are a few other thoughts to add to the argument for more study of the issue.

The downstream effects of a screening radiographic finding are the true cost and morbidity issue. In almost all cases, a minor surgery (in this case, a simple lumpectomy) for a mass is preferable to the consumer. The next steps of a lymph node dissection, radiation, hormonal therapy, and chemotherapy are where costs and complications arise. We need to better understand, likely through genomic testing and molecular profiling, which tumors can be treated with minimal surgery and then routine observation. The "ostrich" approach of simply not looking seems to make little sense. Waiting until all breast cancers are palpable is a slippery slope to contemplate, and most certainly will lead to poorer outcomes.

Let the Individual Decide

Maurie Markman, M.D.

Senior Vice President of Clinical Affairs and

National Director of Medical Oncology

Cancer Treatment Centers of America (CTCA)

Philadelphia

Associate editor, The Oncology Report

I agree with the thoughtful comments of Dr. Loprinzi and Dr. Burris.

One additional comment relates to who should be making the decisions regarding whether screening is appropriate for a particular individual. And I would argue strongly that it is the individual, and not some government agency. Clearly, it is essential that such decisions be informed by any available current and future research/data, but the relative importance of the benefits and risks associated with this approach to cancer management can only be assigned by the individual.

The New England Journal of Medicine study contends that more than 1 million women were overdiagnosed with breast cancer – and overtreated – as a result of screening mammography. How does this affect your thinking on screening mammography – and will it affect practice?

Not Convinced That Change is Called For

Charles B. Hammond, M.D.,

Professor and Chairman Emeritus in the Department of Obstetrics and Gynecology

Duke University

Durham, N.C.

Editorial Advisory Board, Ob.Gyn. News

The NEJM findings do not convince me to change my approach to breast cancer screening. If a woman has no family history or findings on physical examination, I recommend a baseline mammogram at age 35 years, with no more until age 40 years, and then a mammogram every year thereafter. If a woman has a significant family history, I try to get markers on that individual, then repeat mammograms from 35 years on. If the markers are positive, I use other studies with more sensitivity, such as computed tomography, etc.

You can see I am aggressive about this subject. Even with the false positives and surgery involved, this is what I recommend to my patients. I realize this is costly in dollars and in terms of increased concerns for the patients, and that there are low but real risks of surgical complications. I also still advise self breast exams and physician exams yearly, or whenever patients have concerns from their breast self exams. I know mammograms are not perfect and there are false positives and false negatives, but that is what I do and will do until other, better tests are developed.

Follow the Guidelines in Place

Sandra M. Swain, M.D.

President, American Society of Clinical Oncology

Medical Director, Washington Cancer Institute, Washington Hospital Center

Professor of Medicine

Georgetown University

Washington

Women should continue to follow the guidelines that are in place which recommend regular screening. Extensive evidence shows regular screening is important for some women, but more research into the biology of the tumors will be critical to establish which women will benefit most.

Consider the Good and the Bad – and Keep Questioning the Status Quo

Charles Loprinzi, M.D.

Regis Professor of Breast Cancer Research

Division of Medical Oncology

Mayo Clinic

Rochester, Minn.

Associate editor, The Oncology Report

Screening for any cancer (including mammography for breast cancer) can result in good and bad. The good is fairly well appreciated – that is, that a cancer is detected at an early stage, allowing the patient to be treated and cured, when the natural history of the cancer would have been to cause morbidity and/or kill the patient.

However, several bad things can occur with screening, including:

• A false positive result. This can lead to increased concern, testing, and treatment (e.g., bilateral prophylactic mastectomies) for nondisease.

• A false negative result. This may be detrimental in that a patient with a recent normal screening test may ignore a subsequent lump or symptom (that may actually represent a cancer), as she was falsely reassured by the negative test result.

• Finding a cancer that would never have caused morbidity or mortality.

• Finding a cancer that would cause morbidity or mortality but still does (on the same timelines) despite early treatment, thus subjecting the patient to earlier treatment morbidities.

• Diagnosing a cancer and initiating treatment that leads to subsequent major morbidity or mortality, earlier than the cancer would have naturally caused (e.g., a treatment-related leukemia).

• A diagnosis of cancer that leads to treatment (e.g., surgery, radiation therapy, and chemotherapy), with a later determination (by expert pathology review) that the cancer diagnosis was wrong.

For all of these reasons, we need to continue to study and question what we are doing with cancer screening, despite the social and political backlashes that sometimes occur with reports that question the status quo.

The "Ostrich Approach" Makes Little Sense

Howard A. Burris III, M.D.

Chief Medical Officer

Executive Director, Drug Development Program

Sarah Cannon Research Institute

Nashville, Tenn.

Editor-in-chief, The Oncology Report

I agree with Dr. Loprinzi’s thoughtful and well-articulated arguments. Following are a few other thoughts to add to the argument for more study of the issue.

The downstream effects of a screening radiographic finding are the true cost and morbidity issue. In almost all cases, a minor surgery (in this case, a simple lumpectomy) for a mass is preferable to the consumer. The next steps of a lymph node dissection, radiation, hormonal therapy, and chemotherapy are where costs and complications arise. We need to better understand, likely through genomic testing and molecular profiling, which tumors can be treated with minimal surgery and then routine observation. The "ostrich" approach of simply not looking seems to make little sense. Waiting until all breast cancers are palpable is a slippery slope to contemplate, and most certainly will lead to poorer outcomes.

Let the Individual Decide

Maurie Markman, M.D.

Senior Vice President of Clinical Affairs and

National Director of Medical Oncology

Cancer Treatment Centers of America (CTCA)

Philadelphia

Associate editor, The Oncology Report

I agree with the thoughtful comments of Dr. Loprinzi and Dr. Burris.

One additional comment relates to who should be making the decisions regarding whether screening is appropriate for a particular individual. And I would argue strongly that it is the individual, and not some government agency. Clearly, it is essential that such decisions be informed by any available current and future research/data, but the relative importance of the benefits and risks associated with this approach to cancer management can only be assigned by the individual.

The New England Journal of Medicine study contends that more than 1 million women were overdiagnosed with breast cancer – and overtreated – as a result of screening mammography. How does this affect your thinking on screening mammography – and will it affect practice?

Not Convinced That Change is Called For

Charles B. Hammond, M.D.,

Professor and Chairman Emeritus in the Department of Obstetrics and Gynecology

Duke University

Durham, N.C.

Editorial Advisory Board, Ob.Gyn. News

The NEJM findings do not convince me to change my approach to breast cancer screening. If a woman has no family history or findings on physical examination, I recommend a baseline mammogram at age 35 years, with no more until age 40 years, and then a mammogram every year thereafter. If a woman has a significant family history, I try to get markers on that individual, then repeat mammograms from 35 years on. If the markers are positive, I use other studies with more sensitivity, such as computed tomography, etc.

You can see I am aggressive about this subject. Even with the false positives and surgery involved, this is what I recommend to my patients. I realize this is costly in dollars and in terms of increased concerns for the patients, and that there are low but real risks of surgical complications. I also still advise self breast exams and physician exams yearly, or whenever patients have concerns from their breast self exams. I know mammograms are not perfect and there are false positives and false negatives, but that is what I do and will do until other, better tests are developed.

Follow the Guidelines in Place

Sandra M. Swain, M.D.

President, American Society of Clinical Oncology

Medical Director, Washington Cancer Institute, Washington Hospital Center

Professor of Medicine

Georgetown University

Washington

Women should continue to follow the guidelines that are in place which recommend regular screening. Extensive evidence shows regular screening is important for some women, but more research into the biology of the tumors will be critical to establish which women will benefit most.

Consider the Good and the Bad – and Keep Questioning the Status Quo

Charles Loprinzi, M.D.

Regis Professor of Breast Cancer Research

Division of Medical Oncology

Mayo Clinic

Rochester, Minn.

Associate editor, The Oncology Report

Screening for any cancer (including mammography for breast cancer) can result in good and bad. The good is fairly well appreciated – that is, that a cancer is detected at an early stage, allowing the patient to be treated and cured, when the natural history of the cancer would have been to cause morbidity and/or kill the patient.

However, several bad things can occur with screening, including:

• A false positive result. This can lead to increased concern, testing, and treatment (e.g., bilateral prophylactic mastectomies) for nondisease.

• A false negative result. This may be detrimental in that a patient with a recent normal screening test may ignore a subsequent lump or symptom (that may actually represent a cancer), as she was falsely reassured by the negative test result.

• Finding a cancer that would never have caused morbidity or mortality.

• Finding a cancer that would cause morbidity or mortality but still does (on the same timelines) despite early treatment, thus subjecting the patient to earlier treatment morbidities.

• Diagnosing a cancer and initiating treatment that leads to subsequent major morbidity or mortality, earlier than the cancer would have naturally caused (e.g., a treatment-related leukemia).

• A diagnosis of cancer that leads to treatment (e.g., surgery, radiation therapy, and chemotherapy), with a later determination (by expert pathology review) that the cancer diagnosis was wrong.

For all of these reasons, we need to continue to study and question what we are doing with cancer screening, despite the social and political backlashes that sometimes occur with reports that question the status quo.

The "Ostrich Approach" Makes Little Sense

Howard A. Burris III, M.D.

Chief Medical Officer

Executive Director, Drug Development Program

Sarah Cannon Research Institute

Nashville, Tenn.

Editor-in-chief, The Oncology Report

I agree with Dr. Loprinzi’s thoughtful and well-articulated arguments. Following are a few other thoughts to add to the argument for more study of the issue.

The downstream effects of a screening radiographic finding are the true cost and morbidity issue. In almost all cases, a minor surgery (in this case, a simple lumpectomy) for a mass is preferable to the consumer. The next steps of a lymph node dissection, radiation, hormonal therapy, and chemotherapy are where costs and complications arise. We need to better understand, likely through genomic testing and molecular profiling, which tumors can be treated with minimal surgery and then routine observation. The "ostrich" approach of simply not looking seems to make little sense. Waiting until all breast cancers are palpable is a slippery slope to contemplate, and most certainly will lead to poorer outcomes.

Let the Individual Decide

Maurie Markman, M.D.

Senior Vice President of Clinical Affairs and

National Director of Medical Oncology

Cancer Treatment Centers of America (CTCA)

Philadelphia

Associate editor, The Oncology Report

I agree with the thoughtful comments of Dr. Loprinzi and Dr. Burris.

One additional comment relates to who should be making the decisions regarding whether screening is appropriate for a particular individual. And I would argue strongly that it is the individual, and not some government agency. Clearly, it is essential that such decisions be informed by any available current and future research/data, but the relative importance of the benefits and risks associated with this approach to cancer management can only be assigned by the individual.

Over the past 3 decades, screening mammography may have overdiagnosed more than a million clinically insignificant breast tumors, while having virtually no impact on the incidence of metastatic disease.

Compared with the premammography era, routine screening now picks up 122 additional cases of early cancer per 100,000 women – just eight of which would likely have progressed to distant disease, Dr. Archie Bleyer and Dr. Gilbert Welch wrote in the Nov. 22 issue of the New England Journal of Medicine.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

Looking at the results in light of a corresponding 28% decrease in breast cancer mortality puts screening mammography in perspective, the authors said: "Our data show that the true contribution of mammography to decreasing mortality must be at the low end of this range. They suggest that mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality – a reduction in the number of women who present with late-stage cancer.

Population cancer screening is a doubled-edged sword, wrote Dr. Bleyer of Oregon Health and Science University in Portland, and Dr. Welch of Geisel School of Medicine at Dartmouth in Hanover, N.H. While it’s impossible to say which screen-detected cancers would have caused serious disease or death, "there is certainty about what happens to [these women]. They undergo surgery, radiation therapy, hormonal therapy for 5 years or more, chemotherapy, or (usually) a combination of these treatments for abnormalities that otherwise would not have caused illness."

The authors used the Surveillance , Epidemiology, and End Results (SEER) database to examine screening mammography and breast cancer incidence data from 1976-2008. They considered the incidence baseline to be the number of cancers reported from 1976-1978, and compared it with incidence in 2006-2008. All of the models in the study controlled for an upswing of breast cancer from 1990 to 2005, which was associated with hormone-replacement therapy.

Screening mammography increased from about 30% of women aged 40 or older in the mid-80s to almost 70% by 2008. This was mirrored by an increase in the diagnosis of early-stage breast cancers diagnosed, from 112/100,000 to 234/100,000 per year – representing an absolute increase of 122/100,000 (N. Engl. J. Med. 2012;367:1998-2005 [doi:10.1056/NEJMoa1206809]).

"[This] reflects both the detection of more cases of localized disease and the advent of the detection of [ductal carcinoma in situ] (which was virtually not detected before mammography was available)," the authors said.

There was a much smaller concomitant decrease in late-stage cancers, which fell from 102/100,000 to 94 /100,000 women. This was almost entirely driven by a drop in regional disease, from about 85/100,000 in 1976 to 78/100,000 in 2008. The incidence of distant disease was almost entirely unchanged, hovering around 17/100,000 for the entire study period.

"If a constant underlying disease burden is assumed, only 8 of the 122 additional early diagnoses were destined to progress to advanced disease, implying a detection of 114 excess cases per 100,000 women" – a total of more than 1.5 million over the study period.

The incidence of overdiagnosis held when the authors used other models designed to favor mammography’s impact.

In a "best-guess estimate," they assumed that breast cancer incidence increased by 0.25% over the study period. "This approach suggests that the excess detection attributable to mammography ... involved more than 1.3 million women in the past 30 years."

The "extreme" model assumed that incidence increased by 0.5% each year, an estimate that minimized surplus diagnoses of early-stage disease and maximized the deficit of late-stage cancer. This model found that screening mammography detected an excess of 1.2 million cancers over the study period.

The "very extreme assumption" model assumed that incidence increased by 0.5% each year, and that the baseline incidence of late-stage disease was the highest ever observed (113 cases per 100,000 women, in 1985). Even with this model – the most favorable toward mammography – the authors estimated overdiagnosis of slightly more than 1 million women.

"Our analysis suggests that whatever the mortality benefit, breast-cancer screening involved substantial harm of excess detection of additional early-stage cancers that was not matched by a reduction in late-stage cancers. This imbalance indicates a considerable amount of overdiagnosis involving more than 1 million women in the past 3 decades – and, according to our best-guess estimate, more than 70,000 women in 2008."

SEER breast cancer mortality data help put the findings into perspective, the authors said. There has been a substantial reduction in mortality, which fell from 71/100,000 to 51/100,000 over the study period. "This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment," they said. But because the absolute reduction in deaths (20/100,000) was larger than the absolute reduction in late-stage cancer (8/100,000), screening mammography can’t be the main driver of change.

"Furthermore ... the small reduction in cases of late-stage cancer that has occurred has been confined to regional (largely node-positive) disease – a stage that can now often be treated successfully, with an expected 5-year survival rate of 85% among women 40 years of age or older. Unfortunately, however, the number of women in the United States who present with distant disease, only 25% of whom survive for 5 years, appears not to have been affected by screening."

Better therapy may even have altered the impact of screening, they added.

"Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of [disease detected by methods other than screening] improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia."

The findings show that there are not absolutes for women considering whether or not to get a mammogram.

"Proponents of screening should provide women with data from a randomized screening trial that reflects improvements in current therapy and includes strategies to mitigate overdiagnosis in the intervention group. Women should recognize that our study does not answer the question, ‘Should I be screened for breast cancer?’ However, they can rest assured that the question has more than one right answer."

Dr. Bleyer disclosed that he is a consultant and speaker for Sigma-Tau Pharmaceuticals. Dr. Welch disclosed that he speaks on the topic of overdiagnosis with universities and medical schools, as well as to the Pharmacy Benefit Management Institute; all honoraria were donated to charitable organizations.

Over the past 3 decades, screening mammography may have overdiagnosed more than a million clinically insignificant breast tumors, while having virtually no impact on the incidence of metastatic disease.

Compared with the premammography era, routine screening now picks up 122 additional cases of early cancer per 100,000 women – just eight of which would likely have progressed to distant disease, Dr. Archie Bleyer and Dr. Gilbert Welch wrote in the Nov. 22 issue of the New England Journal of Medicine.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

Looking at the results in light of a corresponding 28% decrease in breast cancer mortality puts screening mammography in perspective, the authors said: "Our data show that the true contribution of mammography to decreasing mortality must be at the low end of this range. They suggest that mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality – a reduction in the number of women who present with late-stage cancer.

Population cancer screening is a doubled-edged sword, wrote Dr. Bleyer of Oregon Health and Science University in Portland, and Dr. Welch of Geisel School of Medicine at Dartmouth in Hanover, N.H. While it’s impossible to say which screen-detected cancers would have caused serious disease or death, "there is certainty about what happens to [these women]. They undergo surgery, radiation therapy, hormonal therapy for 5 years or more, chemotherapy, or (usually) a combination of these treatments for abnormalities that otherwise would not have caused illness."

The authors used the Surveillance , Epidemiology, and End Results (SEER) database to examine screening mammography and breast cancer incidence data from 1976-2008. They considered the incidence baseline to be the number of cancers reported from 1976-1978, and compared it with incidence in 2006-2008. All of the models in the study controlled for an upswing of breast cancer from 1990 to 2005, which was associated with hormone-replacement therapy.

Screening mammography increased from about 30% of women aged 40 or older in the mid-80s to almost 70% by 2008. This was mirrored by an increase in the diagnosis of early-stage breast cancers diagnosed, from 112/100,000 to 234/100,000 per year – representing an absolute increase of 122/100,000 (N. Engl. J. Med. 2012;367:1998-2005 [doi:10.1056/NEJMoa1206809]).

"[This] reflects both the detection of more cases of localized disease and the advent of the detection of [ductal carcinoma in situ] (which was virtually not detected before mammography was available)," the authors said.

There was a much smaller concomitant decrease in late-stage cancers, which fell from 102/100,000 to 94 /100,000 women. This was almost entirely driven by a drop in regional disease, from about 85/100,000 in 1976 to 78/100,000 in 2008. The incidence of distant disease was almost entirely unchanged, hovering around 17/100,000 for the entire study period.

"If a constant underlying disease burden is assumed, only 8 of the 122 additional early diagnoses were destined to progress to advanced disease, implying a detection of 114 excess cases per 100,000 women" – a total of more than 1.5 million over the study period.

The incidence of overdiagnosis held when the authors used other models designed to favor mammography’s impact.

In a "best-guess estimate," they assumed that breast cancer incidence increased by 0.25% over the study period. "This approach suggests that the excess detection attributable to mammography ... involved more than 1.3 million women in the past 30 years."

The "extreme" model assumed that incidence increased by 0.5% each year, an estimate that minimized surplus diagnoses of early-stage disease and maximized the deficit of late-stage cancer. This model found that screening mammography detected an excess of 1.2 million cancers over the study period.

The "very extreme assumption" model assumed that incidence increased by 0.5% each year, and that the baseline incidence of late-stage disease was the highest ever observed (113 cases per 100,000 women, in 1985). Even with this model – the most favorable toward mammography – the authors estimated overdiagnosis of slightly more than 1 million women.

"Our analysis suggests that whatever the mortality benefit, breast-cancer screening involved substantial harm of excess detection of additional early-stage cancers that was not matched by a reduction in late-stage cancers. This imbalance indicates a considerable amount of overdiagnosis involving more than 1 million women in the past 3 decades – and, according to our best-guess estimate, more than 70,000 women in 2008."

SEER breast cancer mortality data help put the findings into perspective, the authors said. There has been a substantial reduction in mortality, which fell from 71/100,000 to 51/100,000 over the study period. "This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment," they said. But because the absolute reduction in deaths (20/100,000) was larger than the absolute reduction in late-stage cancer (8/100,000), screening mammography can’t be the main driver of change.

"Furthermore ... the small reduction in cases of late-stage cancer that has occurred has been confined to regional (largely node-positive) disease – a stage that can now often be treated successfully, with an expected 5-year survival rate of 85% among women 40 years of age or older. Unfortunately, however, the number of women in the United States who present with distant disease, only 25% of whom survive for 5 years, appears not to have been affected by screening."

Better therapy may even have altered the impact of screening, they added.

"Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of [disease detected by methods other than screening] improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia."

The findings show that there are not absolutes for women considering whether or not to get a mammogram.

"Proponents of screening should provide women with data from a randomized screening trial that reflects improvements in current therapy and includes strategies to mitigate overdiagnosis in the intervention group. Women should recognize that our study does not answer the question, ‘Should I be screened for breast cancer?’ However, they can rest assured that the question has more than one right answer."

Dr. Bleyer disclosed that he is a consultant and speaker for Sigma-Tau Pharmaceuticals. Dr. Welch disclosed that he speaks on the topic of overdiagnosis with universities and medical schools, as well as to the Pharmacy Benefit Management Institute; all honoraria were donated to charitable organizations.

Over the past 3 decades, screening mammography may have overdiagnosed more than a million clinically insignificant breast tumors, while having virtually no impact on the incidence of metastatic disease.

Compared with the premammography era, routine screening now picks up 122 additional cases of early cancer per 100,000 women – just eight of which would likely have progressed to distant disease, Dr. Archie Bleyer and Dr. Gilbert Welch wrote in the Nov. 22 issue of the New England Journal of Medicine.

Courtesy Rhoda Baer/National Cancer Institute (NCI)

Looking at the results in light of a corresponding 28% decrease in breast cancer mortality puts screening mammography in perspective, the authors said: "Our data show that the true contribution of mammography to decreasing mortality must be at the low end of this range. They suggest that mammography has largely not met the first prerequisite for screening to reduce cancer-specific mortality – a reduction in the number of women who present with late-stage cancer.

Population cancer screening is a doubled-edged sword, wrote Dr. Bleyer of Oregon Health and Science University in Portland, and Dr. Welch of Geisel School of Medicine at Dartmouth in Hanover, N.H. While it’s impossible to say which screen-detected cancers would have caused serious disease or death, "there is certainty about what happens to [these women]. They undergo surgery, radiation therapy, hormonal therapy for 5 years or more, chemotherapy, or (usually) a combination of these treatments for abnormalities that otherwise would not have caused illness."

The authors used the Surveillance , Epidemiology, and End Results (SEER) database to examine screening mammography and breast cancer incidence data from 1976-2008. They considered the incidence baseline to be the number of cancers reported from 1976-1978, and compared it with incidence in 2006-2008. All of the models in the study controlled for an upswing of breast cancer from 1990 to 2005, which was associated with hormone-replacement therapy.

Screening mammography increased from about 30% of women aged 40 or older in the mid-80s to almost 70% by 2008. This was mirrored by an increase in the diagnosis of early-stage breast cancers diagnosed, from 112/100,000 to 234/100,000 per year – representing an absolute increase of 122/100,000 (N. Engl. J. Med. 2012;367:1998-2005 [doi:10.1056/NEJMoa1206809]).

"[This] reflects both the detection of more cases of localized disease and the advent of the detection of [ductal carcinoma in situ] (which was virtually not detected before mammography was available)," the authors said.

There was a much smaller concomitant decrease in late-stage cancers, which fell from 102/100,000 to 94 /100,000 women. This was almost entirely driven by a drop in regional disease, from about 85/100,000 in 1976 to 78/100,000 in 2008. The incidence of distant disease was almost entirely unchanged, hovering around 17/100,000 for the entire study period.

"If a constant underlying disease burden is assumed, only 8 of the 122 additional early diagnoses were destined to progress to advanced disease, implying a detection of 114 excess cases per 100,000 women" – a total of more than 1.5 million over the study period.

The incidence of overdiagnosis held when the authors used other models designed to favor mammography’s impact.

In a "best-guess estimate," they assumed that breast cancer incidence increased by 0.25% over the study period. "This approach suggests that the excess detection attributable to mammography ... involved more than 1.3 million women in the past 30 years."

The "extreme" model assumed that incidence increased by 0.5% each year, an estimate that minimized surplus diagnoses of early-stage disease and maximized the deficit of late-stage cancer. This model found that screening mammography detected an excess of 1.2 million cancers over the study period.

The "very extreme assumption" model assumed that incidence increased by 0.5% each year, and that the baseline incidence of late-stage disease was the highest ever observed (113 cases per 100,000 women, in 1985). Even with this model – the most favorable toward mammography – the authors estimated overdiagnosis of slightly more than 1 million women.

"Our analysis suggests that whatever the mortality benefit, breast-cancer screening involved substantial harm of excess detection of additional early-stage cancers that was not matched by a reduction in late-stage cancers. This imbalance indicates a considerable amount of overdiagnosis involving more than 1 million women in the past 3 decades – and, according to our best-guess estimate, more than 70,000 women in 2008."

SEER breast cancer mortality data help put the findings into perspective, the authors said. There has been a substantial reduction in mortality, which fell from 71/100,000 to 51/100,000 over the study period. "This reduction in mortality is probably due to some combination of the effects of screening mammography and better treatment," they said. But because the absolute reduction in deaths (20/100,000) was larger than the absolute reduction in late-stage cancer (8/100,000), screening mammography can’t be the main driver of change.

"Furthermore ... the small reduction in cases of late-stage cancer that has occurred has been confined to regional (largely node-positive) disease – a stage that can now often be treated successfully, with an expected 5-year survival rate of 85% among women 40 years of age or older. Unfortunately, however, the number of women in the United States who present with distant disease, only 25% of whom survive for 5 years, appears not to have been affected by screening."

Better therapy may even have altered the impact of screening, they added.

"Ironically, improvements in treatment tend to deteriorate the benefit of screening. As treatment of [disease detected by methods other than screening] improves, the benefit of screening diminishes. For example, since pneumonia can be treated successfully, no one would suggest that we screen for pneumonia."

The findings show that there are not absolutes for women considering whether or not to get a mammogram.

"Proponents of screening should provide women with data from a randomized screening trial that reflects improvements in current therapy and includes strategies to mitigate overdiagnosis in the intervention group. Women should recognize that our study does not answer the question, ‘Should I be screened for breast cancer?’ However, they can rest assured that the question has more than one right answer."

Dr. Bleyer disclosed that he is a consultant and speaker for Sigma-Tau Pharmaceuticals. Dr. Welch disclosed that he speaks on the topic of overdiagnosis with universities and medical schools, as well as to the Pharmacy Benefit Management Institute; all honoraria were donated to charitable organizations.

BOSTON – Cosmetic results were significantly worse after 3 years for women who had accelerated partial-breast irradiation than for women treated with whole-breast irradiation in a randomized clinical trial, investigators found.

Nearly a third (32%) of women who underwent accelerated partial breast irradiation (APBI) with a 3-D conformal technique had cosmetic results rated as fair or poor by a nurse, compared with 19% of women who had undergone whole-breast irradiation (WBI), Dr. Timothy J. Whelan reported at the annual meeting of the American Society for Radiation Oncology.

APBI was also associated with more grade 1 and 2 toxicities than WBI, but there were few grade 3 toxicities with either technique and no grade 4 toxicities, said Dr. Whelan, a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ont.

"This increase in toxicity may have resulted from limited conformality of the 3-D conformal approach, the short time between the fractions – radiation with APBI was given twice a day with 6 hours between the fractions, which may not have been adequate – and maybe due to the asymmetric nature of partial breast irradiation itself, given that it’s only given to part of the breast," he said at a press briefing.

Trading Convenience for Toxicity?

APBI – in which a large dose per fraction of external beam radiation is given only to the surgical cavity with an additional safety margin – allows radiation therapy to be delivered in 1 week or less, making it an attractive alternative to multifraction therapy that can stretch over many weeks.

But it is still not clear whether APBI trades poorer outcomes for convenience, Dr. Whelan said. He and colleagues in Canada, Australia, and New Zealand conducted the RAPID trial (Randomized Trial of Accelerated Partial-Breast Irradiation Using 3-D Conformal External Beam Radiation Therapy) to find out. The study compared the efficacy and safety of the two modalities in women over 40 years of age with invasive or noninvasive breast cancers smaller than 3 cm.

Investigators enrolled 2,135 patients and randomized them to receive either WBI (1,065 patients) at 50 Gy in 25 fractions or 42.5 Gy in 16 fractions given once daily with or without boost irradiation or 3-D conformal APBI at 38.5 Gy in 10 fractions twice daily (1,070 patients). Cosmetic results were rated by a trained nurse on a global assessment using the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System for Breast Cancer, and for toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Radiologists blinded to treatment type also rated results on digital photographs.

Immediately after radiation, cosmetic results were similar between the groups, with nurse-assessed appearance rated as fair or poor in 17% of women who had WBI, and 19% who had APBI (P = .35). However, an interim toxicity analysis among 850 evaluable patients, showed that at 3 years (2.3 years median follow-up) 13% more of the patients who had undergone APBI had fair or poor cosmesis.

The Jury Is Out

Dr. Whelan noted that the between-group differences were about the same at 5 years, but did not provide data.

"The evidence for partial-breast irradiation is still not very clear. We don’t have very robust evidence about its efficacy, and we just now have recent evidence about its potential toxicities, he said.

Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey in New Brunswick, commented that "the results from the RAPID trial shed further light on the use of accelerated partial-breast irradiation, and emphasize the need to further investigate these fractionation schemes and sort out whether in fact the toxicity from partial-breast irradiation may be slightly worse than with whole-breast irradiation."

Dr. Haffty moderated a briefing where the data were presented, but was not involved in the RAPID trial.

The RAPID trial is supported by the Canadian Institutes of Health Research and Canadian Breast Cancer Research Alliance. Dr. Whelan has received honoraria from AstraZeneca and Novartis. Dr. Haffty reported no relevant disclosures.

BOSTON – Cosmetic results were significantly worse after 3 years for women who had accelerated partial-breast irradiation than for women treated with whole-breast irradiation in a randomized clinical trial, investigators found.

Nearly a third (32%) of women who underwent accelerated partial breast irradiation (APBI) with a 3-D conformal technique had cosmetic results rated as fair or poor by a nurse, compared with 19% of women who had undergone whole-breast irradiation (WBI), Dr. Timothy J. Whelan reported at the annual meeting of the American Society for Radiation Oncology.

APBI was also associated with more grade 1 and 2 toxicities than WBI, but there were few grade 3 toxicities with either technique and no grade 4 toxicities, said Dr. Whelan, a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ont.

"This increase in toxicity may have resulted from limited conformality of the 3-D conformal approach, the short time between the fractions – radiation with APBI was given twice a day with 6 hours between the fractions, which may not have been adequate – and maybe due to the asymmetric nature of partial breast irradiation itself, given that it’s only given to part of the breast," he said at a press briefing.

Trading Convenience for Toxicity?

APBI – in which a large dose per fraction of external beam radiation is given only to the surgical cavity with an additional safety margin – allows radiation therapy to be delivered in 1 week or less, making it an attractive alternative to multifraction therapy that can stretch over many weeks.

But it is still not clear whether APBI trades poorer outcomes for convenience, Dr. Whelan said. He and colleagues in Canada, Australia, and New Zealand conducted the RAPID trial (Randomized Trial of Accelerated Partial-Breast Irradiation Using 3-D Conformal External Beam Radiation Therapy) to find out. The study compared the efficacy and safety of the two modalities in women over 40 years of age with invasive or noninvasive breast cancers smaller than 3 cm.

Investigators enrolled 2,135 patients and randomized them to receive either WBI (1,065 patients) at 50 Gy in 25 fractions or 42.5 Gy in 16 fractions given once daily with or without boost irradiation or 3-D conformal APBI at 38.5 Gy in 10 fractions twice daily (1,070 patients). Cosmetic results were rated by a trained nurse on a global assessment using the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System for Breast Cancer, and for toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Radiologists blinded to treatment type also rated results on digital photographs.

Immediately after radiation, cosmetic results were similar between the groups, with nurse-assessed appearance rated as fair or poor in 17% of women who had WBI, and 19% who had APBI (P = .35). However, an interim toxicity analysis among 850 evaluable patients, showed that at 3 years (2.3 years median follow-up) 13% more of the patients who had undergone APBI had fair or poor cosmesis.

The Jury Is Out

Dr. Whelan noted that the between-group differences were about the same at 5 years, but did not provide data.

"The evidence for partial-breast irradiation is still not very clear. We don’t have very robust evidence about its efficacy, and we just now have recent evidence about its potential toxicities, he said.

Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey in New Brunswick, commented that "the results from the RAPID trial shed further light on the use of accelerated partial-breast irradiation, and emphasize the need to further investigate these fractionation schemes and sort out whether in fact the toxicity from partial-breast irradiation may be slightly worse than with whole-breast irradiation."

Dr. Haffty moderated a briefing where the data were presented, but was not involved in the RAPID trial.

The RAPID trial is supported by the Canadian Institutes of Health Research and Canadian Breast Cancer Research Alliance. Dr. Whelan has received honoraria from AstraZeneca and Novartis. Dr. Haffty reported no relevant disclosures.

BOSTON – Cosmetic results were significantly worse after 3 years for women who had accelerated partial-breast irradiation than for women treated with whole-breast irradiation in a randomized clinical trial, investigators found.

Nearly a third (32%) of women who underwent accelerated partial breast irradiation (APBI) with a 3-D conformal technique had cosmetic results rated as fair or poor by a nurse, compared with 19% of women who had undergone whole-breast irradiation (WBI), Dr. Timothy J. Whelan reported at the annual meeting of the American Society for Radiation Oncology.

APBI was also associated with more grade 1 and 2 toxicities than WBI, but there were few grade 3 toxicities with either technique and no grade 4 toxicities, said Dr. Whelan, a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ont.

"This increase in toxicity may have resulted from limited conformality of the 3-D conformal approach, the short time between the fractions – radiation with APBI was given twice a day with 6 hours between the fractions, which may not have been adequate – and maybe due to the asymmetric nature of partial breast irradiation itself, given that it’s only given to part of the breast," he said at a press briefing.

Trading Convenience for Toxicity?

APBI – in which a large dose per fraction of external beam radiation is given only to the surgical cavity with an additional safety margin – allows radiation therapy to be delivered in 1 week or less, making it an attractive alternative to multifraction therapy that can stretch over many weeks.

But it is still not clear whether APBI trades poorer outcomes for convenience, Dr. Whelan said. He and colleagues in Canada, Australia, and New Zealand conducted the RAPID trial (Randomized Trial of Accelerated Partial-Breast Irradiation Using 3-D Conformal External Beam Radiation Therapy) to find out. The study compared the efficacy and safety of the two modalities in women over 40 years of age with invasive or noninvasive breast cancers smaller than 3 cm.

Investigators enrolled 2,135 patients and randomized them to receive either WBI (1,065 patients) at 50 Gy in 25 fractions or 42.5 Gy in 16 fractions given once daily with or without boost irradiation or 3-D conformal APBI at 38.5 Gy in 10 fractions twice daily (1,070 patients). Cosmetic results were rated by a trained nurse on a global assessment using the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System for Breast Cancer, and for toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Radiologists blinded to treatment type also rated results on digital photographs.

Immediately after radiation, cosmetic results were similar between the groups, with nurse-assessed appearance rated as fair or poor in 17% of women who had WBI, and 19% who had APBI (P = .35). However, an interim toxicity analysis among 850 evaluable patients, showed that at 3 years (2.3 years median follow-up) 13% more of the patients who had undergone APBI had fair or poor cosmesis.

The Jury Is Out

Dr. Whelan noted that the between-group differences were about the same at 5 years, but did not provide data.

"The evidence for partial-breast irradiation is still not very clear. We don’t have very robust evidence about its efficacy, and we just now have recent evidence about its potential toxicities, he said.

Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey in New Brunswick, commented that "the results from the RAPID trial shed further light on the use of accelerated partial-breast irradiation, and emphasize the need to further investigate these fractionation schemes and sort out whether in fact the toxicity from partial-breast irradiation may be slightly worse than with whole-breast irradiation."

Dr. Haffty moderated a briefing where the data were presented, but was not involved in the RAPID trial.

The RAPID trial is supported by the Canadian Institutes of Health Research and Canadian Breast Cancer Research Alliance. Dr. Whelan has received honoraria from AstraZeneca and Novartis. Dr. Haffty reported no relevant disclosures.