Breast Cancer

SAN ANTONIO – Adding the investigational antiangiogenesis agent ramucirumab to first-line chemotherapy did not significantly benefit metastatic breast cancer patients in a large phase III trial, Dr. John R. Mackey said at the San Antonio Breast Cancer Symposium.

The ROSE/TRIO-12 trial included 1,144 metastatic breast cancer patients in 25 countries who were randomized 2:1 to first-line docetaxel plus ramucirumab, a recombinant human IgG1 monoclonal antibody that binds to vascular endothelial growth factor receptor-2, or to docetaxel and placebo. After a median follow-up of 16.2 months, investigator-assessed progression-free survival was 9.5 months in the ramucirumab group and was not significantly different at 8.2 months in controls. No clinically defined subgroup showed a benefit with combination therapy, reported Dr. Mackey, professor of oncology at the University of Alberta, Edmonton, and director of Translational Research in Oncology (TRIO), which conducted the trial.

Median overall survival was 27.3 months with ramucirumab and 27.2 months in controls. However, the overall response rate, disease control rate, and time to progression were greater in the combined therapy group.

"We’re hopeful that we can go back to the tissue samples and find predictive biomarkers because there is a signal here. We are seeing improvements in several endpoints and some patients clearly are benefiting, but we do not understand the biology sufficiently well to be able to pick them out of the general population," he said.

Dr. Mackey noted that ramucirumab is the focus of a broad phase III clinical trial program. Definitive phase III studies of the antiangiogenesis agent in lung and colon cancer are underway. And two phase III trials in gastric cancer – REGARD and RAINBOW – have been completed with positive results for overall survival. "I think we can say that at least in another disease setting, this agent has activity."

Despite the negative results in ROSE/TRIO-12 plus the negative outcomes for trials of bevacizumab (Avastin), this is not the end of the line for antiangiogenesis agents in breast cancer, said conference codirector Dr. Peter Ravdin of the University of Texas, San Antonio. "Breast cancer is a really diverse disease. Drugs that may on average have little value in breast cancer may be very effective in selected populations."

The ROSE study was funded by Eli Lilly. Dr. Mackey declared having no financial conflicts of interest.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adding the investigational antiangiogenesis agent ramucirumab to first-line chemotherapy did not significantly benefit metastatic breast cancer patients in a large phase III trial, Dr. John R. Mackey said at the San Antonio Breast Cancer Symposium.

The ROSE/TRIO-12 trial included 1,144 metastatic breast cancer patients in 25 countries who were randomized 2:1 to first-line docetaxel plus ramucirumab, a recombinant human IgG1 monoclonal antibody that binds to vascular endothelial growth factor receptor-2, or to docetaxel and placebo. After a median follow-up of 16.2 months, investigator-assessed progression-free survival was 9.5 months in the ramucirumab group and was not significantly different at 8.2 months in controls. No clinically defined subgroup showed a benefit with combination therapy, reported Dr. Mackey, professor of oncology at the University of Alberta, Edmonton, and director of Translational Research in Oncology (TRIO), which conducted the trial.

Median overall survival was 27.3 months with ramucirumab and 27.2 months in controls. However, the overall response rate, disease control rate, and time to progression were greater in the combined therapy group.

"We’re hopeful that we can go back to the tissue samples and find predictive biomarkers because there is a signal here. We are seeing improvements in several endpoints and some patients clearly are benefiting, but we do not understand the biology sufficiently well to be able to pick them out of the general population," he said.

Dr. Mackey noted that ramucirumab is the focus of a broad phase III clinical trial program. Definitive phase III studies of the antiangiogenesis agent in lung and colon cancer are underway. And two phase III trials in gastric cancer – REGARD and RAINBOW – have been completed with positive results for overall survival. "I think we can say that at least in another disease setting, this agent has activity."

Despite the negative results in ROSE/TRIO-12 plus the negative outcomes for trials of bevacizumab (Avastin), this is not the end of the line for antiangiogenesis agents in breast cancer, said conference codirector Dr. Peter Ravdin of the University of Texas, San Antonio. "Breast cancer is a really diverse disease. Drugs that may on average have little value in breast cancer may be very effective in selected populations."

The ROSE study was funded by Eli Lilly. Dr. Mackey declared having no financial conflicts of interest.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adding the investigational antiangiogenesis agent ramucirumab to first-line chemotherapy did not significantly benefit metastatic breast cancer patients in a large phase III trial, Dr. John R. Mackey said at the San Antonio Breast Cancer Symposium.

The ROSE/TRIO-12 trial included 1,144 metastatic breast cancer patients in 25 countries who were randomized 2:1 to first-line docetaxel plus ramucirumab, a recombinant human IgG1 monoclonal antibody that binds to vascular endothelial growth factor receptor-2, or to docetaxel and placebo. After a median follow-up of 16.2 months, investigator-assessed progression-free survival was 9.5 months in the ramucirumab group and was not significantly different at 8.2 months in controls. No clinically defined subgroup showed a benefit with combination therapy, reported Dr. Mackey, professor of oncology at the University of Alberta, Edmonton, and director of Translational Research in Oncology (TRIO), which conducted the trial.

Median overall survival was 27.3 months with ramucirumab and 27.2 months in controls. However, the overall response rate, disease control rate, and time to progression were greater in the combined therapy group.

"We’re hopeful that we can go back to the tissue samples and find predictive biomarkers because there is a signal here. We are seeing improvements in several endpoints and some patients clearly are benefiting, but we do not understand the biology sufficiently well to be able to pick them out of the general population," he said.

Dr. Mackey noted that ramucirumab is the focus of a broad phase III clinical trial program. Definitive phase III studies of the antiangiogenesis agent in lung and colon cancer are underway. And two phase III trials in gastric cancer – REGARD and RAINBOW – have been completed with positive results for overall survival. "I think we can say that at least in another disease setting, this agent has activity."

Despite the negative results in ROSE/TRIO-12 plus the negative outcomes for trials of bevacizumab (Avastin), this is not the end of the line for antiangiogenesis agents in breast cancer, said conference codirector Dr. Peter Ravdin of the University of Texas, San Antonio. "Breast cancer is a really diverse disease. Drugs that may on average have little value in breast cancer may be very effective in selected populations."

The ROSE study was funded by Eli Lilly. Dr. Mackey declared having no financial conflicts of interest.

bjancin@frontlinemedcom.com

Breast cancer chemopreventive drugs such as tamoxifen should be covered as a preventive service with no out-of-pocket cost for high-risk women, according to the Health and Human Services department. But it’s not clear if the HHS clarification of covered preventive benefits under the Affordable Care Act will encourage more primary care physicians to prescribe the medications and more women to take the drugs.

Dr. Jeffery Ward, an oncologist at the Swedish Cancer Institute, Edmonds, Wash., said that he did not think cost was a big obstacle, as tamoxifen is available generically. Concern about side effects and a lack of knowledge among primary care physicians are larger issues, said Dr. Ward, who is the immediate past chairman of the American Society of Clinical Oncology’s clinical practice committee.

The policy – clarified by HHS on Jan. 9 – would apply to group and individual health insurance policies that went into effect after the March 2010 enactment of the Affordable Care Act, as well as those that have been substantially changed since then.

The ACA mandates that services or therapies given an "A" or "B" rating by the U.S. Preventive Services Task Force be covered as preventive care by individual and group health plans and Medicare. States have the option to cover these benefits for Medicaid recipients.

Preventive benefits must be covered with no copayments, deductibles, or other out-of-pocket costs.

The breast cancer prevention coverage must start on or after Sept. 24, 2014, 1 year after the USPSTF first issued a "B" rating also, for use of the selective estrogen receptor modulators, tamoxifen, or raloxifene for women at high-risk for breast cancer and low risk for side effects. ASCO urged use of tamoxifen and raloxifene for breast cancer prevention in guidelines issued in July (J. Clin. Onc. 2013;31:2942-62).

Currently, tamoxifen and raloxifene are the only Food and Drug Administration–approved drugs for breast cancer prevention in high-risk women. Tamoxifen is approved for women aged 35 years and older; and raloxifene for postmenopausal women. The USPSTF backed the use of the FDA-approved therapies only. Likewise, the HHS policy applies to only FDA-approved drugs.

As many of 5% of U.S. women may be eligible for breast cancer chemoprevention, according to Dr. Mark H. Ebell, a USPSTF member and epidemiologist with the University of Georgia, Athens, who spoke with Frontline Medical News after the guidelines were issued. Few seem to be currently taking any of these prevention drugs, however, according to data compiled by the USPSTF. The task force cited surveys showing that, after being told of the risks and benefits, 50%-75% of high-risk women declined to accept a prescription for tamoxifen or raloxifene. Concerns about side effects seemed to be the main concern.

There is also a lag in prescribing. Only 96 of 350 primary care physicians – including ob.gyns – who responded to a survey, said that they had prescribed tamoxifen as a preventive, according to a study.

Dr. Ward said that primary care physicians may not understand who is an appropriate candidate or may be reluctant to refer healthy women to an oncologist. They also might not be comfortable prescribing a medication they regard as a cancer drug, he said. Many of the high-risk women referred to him ultimately end up taking a chemopreventive, he said, adding that for every patient who refuses, there are probably 4 who agree to try the therapy, but "15 after that who never hear about it," because of gaps in knowledge in the primary care setting.

While the HHS clarification will likely help many of his patients, he also sees it leading to some confusion. For instance, patients who already have breast cancer might think that their medications will now be covered without any out-of-pocket costs. "The consequences have not been well thought out," said Dr. Ward, of the coverage policy.

The coverage requirement also gave insurers pause. "We are concerned about the precedent of expanding the definition of prevention to now include some treatments that must be covered with no cost-sharing," said Robert Zirkelbach, a spokesman for America’s Health Insurance Plans (AHIP). He said that while, "helping women with breast cancer get the care they need has long been a top priority for health plans," the cost of therapies that appear to be "free" are actually "reflected in the premiums consumers pay for coverage."

Dr. Ward noted, however, that it might be less expensive for insurers to cover the cost of chemopreventives than for the treatment of a woman with breast cancer.

aault@frontlinemedcom.com

On Twitter @aliciaault

Breast cancer chemopreventive drugs such as tamoxifen should be covered as a preventive service with no out-of-pocket cost for high-risk women, according to the Health and Human Services department. But it’s not clear if the HHS clarification of covered preventive benefits under the Affordable Care Act will encourage more primary care physicians to prescribe the medications and more women to take the drugs.

Dr. Jeffery Ward, an oncologist at the Swedish Cancer Institute, Edmonds, Wash., said that he did not think cost was a big obstacle, as tamoxifen is available generically. Concern about side effects and a lack of knowledge among primary care physicians are larger issues, said Dr. Ward, who is the immediate past chairman of the American Society of Clinical Oncology’s clinical practice committee.

The policy – clarified by HHS on Jan. 9 – would apply to group and individual health insurance policies that went into effect after the March 2010 enactment of the Affordable Care Act, as well as those that have been substantially changed since then.

The ACA mandates that services or therapies given an "A" or "B" rating by the U.S. Preventive Services Task Force be covered as preventive care by individual and group health plans and Medicare. States have the option to cover these benefits for Medicaid recipients.

Preventive benefits must be covered with no copayments, deductibles, or other out-of-pocket costs.

The breast cancer prevention coverage must start on or after Sept. 24, 2014, 1 year after the USPSTF first issued a "B" rating also, for use of the selective estrogen receptor modulators, tamoxifen, or raloxifene for women at high-risk for breast cancer and low risk for side effects. ASCO urged use of tamoxifen and raloxifene for breast cancer prevention in guidelines issued in July (J. Clin. Onc. 2013;31:2942-62).

Currently, tamoxifen and raloxifene are the only Food and Drug Administration–approved drugs for breast cancer prevention in high-risk women. Tamoxifen is approved for women aged 35 years and older; and raloxifene for postmenopausal women. The USPSTF backed the use of the FDA-approved therapies only. Likewise, the HHS policy applies to only FDA-approved drugs.

As many of 5% of U.S. women may be eligible for breast cancer chemoprevention, according to Dr. Mark H. Ebell, a USPSTF member and epidemiologist with the University of Georgia, Athens, who spoke with Frontline Medical News after the guidelines were issued. Few seem to be currently taking any of these prevention drugs, however, according to data compiled by the USPSTF. The task force cited surveys showing that, after being told of the risks and benefits, 50%-75% of high-risk women declined to accept a prescription for tamoxifen or raloxifene. Concerns about side effects seemed to be the main concern.

There is also a lag in prescribing. Only 96 of 350 primary care physicians – including ob.gyns – who responded to a survey, said that they had prescribed tamoxifen as a preventive, according to a study.

Dr. Ward said that primary care physicians may not understand who is an appropriate candidate or may be reluctant to refer healthy women to an oncologist. They also might not be comfortable prescribing a medication they regard as a cancer drug, he said. Many of the high-risk women referred to him ultimately end up taking a chemopreventive, he said, adding that for every patient who refuses, there are probably 4 who agree to try the therapy, but "15 after that who never hear about it," because of gaps in knowledge in the primary care setting.

While the HHS clarification will likely help many of his patients, he also sees it leading to some confusion. For instance, patients who already have breast cancer might think that their medications will now be covered without any out-of-pocket costs. "The consequences have not been well thought out," said Dr. Ward, of the coverage policy.

The coverage requirement also gave insurers pause. "We are concerned about the precedent of expanding the definition of prevention to now include some treatments that must be covered with no cost-sharing," said Robert Zirkelbach, a spokesman for America’s Health Insurance Plans (AHIP). He said that while, "helping women with breast cancer get the care they need has long been a top priority for health plans," the cost of therapies that appear to be "free" are actually "reflected in the premiums consumers pay for coverage."

Dr. Ward noted, however, that it might be less expensive for insurers to cover the cost of chemopreventives than for the treatment of a woman with breast cancer.

aault@frontlinemedcom.com

On Twitter @aliciaault

Breast cancer chemopreventive drugs such as tamoxifen should be covered as a preventive service with no out-of-pocket cost for high-risk women, according to the Health and Human Services department. But it’s not clear if the HHS clarification of covered preventive benefits under the Affordable Care Act will encourage more primary care physicians to prescribe the medications and more women to take the drugs.

Dr. Jeffery Ward, an oncologist at the Swedish Cancer Institute, Edmonds, Wash., said that he did not think cost was a big obstacle, as tamoxifen is available generically. Concern about side effects and a lack of knowledge among primary care physicians are larger issues, said Dr. Ward, who is the immediate past chairman of the American Society of Clinical Oncology’s clinical practice committee.

The policy – clarified by HHS on Jan. 9 – would apply to group and individual health insurance policies that went into effect after the March 2010 enactment of the Affordable Care Act, as well as those that have been substantially changed since then.

The ACA mandates that services or therapies given an "A" or "B" rating by the U.S. Preventive Services Task Force be covered as preventive care by individual and group health plans and Medicare. States have the option to cover these benefits for Medicaid recipients.

Preventive benefits must be covered with no copayments, deductibles, or other out-of-pocket costs.

The breast cancer prevention coverage must start on or after Sept. 24, 2014, 1 year after the USPSTF first issued a "B" rating also, for use of the selective estrogen receptor modulators, tamoxifen, or raloxifene for women at high-risk for breast cancer and low risk for side effects. ASCO urged use of tamoxifen and raloxifene for breast cancer prevention in guidelines issued in July (J. Clin. Onc. 2013;31:2942-62).

Currently, tamoxifen and raloxifene are the only Food and Drug Administration–approved drugs for breast cancer prevention in high-risk women. Tamoxifen is approved for women aged 35 years and older; and raloxifene for postmenopausal women. The USPSTF backed the use of the FDA-approved therapies only. Likewise, the HHS policy applies to only FDA-approved drugs.

As many of 5% of U.S. women may be eligible for breast cancer chemoprevention, according to Dr. Mark H. Ebell, a USPSTF member and epidemiologist with the University of Georgia, Athens, who spoke with Frontline Medical News after the guidelines were issued. Few seem to be currently taking any of these prevention drugs, however, according to data compiled by the USPSTF. The task force cited surveys showing that, after being told of the risks and benefits, 50%-75% of high-risk women declined to accept a prescription for tamoxifen or raloxifene. Concerns about side effects seemed to be the main concern.

There is also a lag in prescribing. Only 96 of 350 primary care physicians – including ob.gyns – who responded to a survey, said that they had prescribed tamoxifen as a preventive, according to a study.

Dr. Ward said that primary care physicians may not understand who is an appropriate candidate or may be reluctant to refer healthy women to an oncologist. They also might not be comfortable prescribing a medication they regard as a cancer drug, he said. Many of the high-risk women referred to him ultimately end up taking a chemopreventive, he said, adding that for every patient who refuses, there are probably 4 who agree to try the therapy, but "15 after that who never hear about it," because of gaps in knowledge in the primary care setting.

While the HHS clarification will likely help many of his patients, he also sees it leading to some confusion. For instance, patients who already have breast cancer might think that their medications will now be covered without any out-of-pocket costs. "The consequences have not been well thought out," said Dr. Ward, of the coverage policy.

The coverage requirement also gave insurers pause. "We are concerned about the precedent of expanding the definition of prevention to now include some treatments that must be covered with no cost-sharing," said Robert Zirkelbach, a spokesman for America’s Health Insurance Plans (AHIP). He said that while, "helping women with breast cancer get the care they need has long been a top priority for health plans," the cost of therapies that appear to be "free" are actually "reflected in the premiums consumers pay for coverage."

Dr. Ward noted, however, that it might be less expensive for insurers to cover the cost of chemopreventives than for the treatment of a woman with breast cancer.

aault@frontlinemedcom.com

On Twitter @aliciaault

Health and Human Services Secretary Kathleen Sebelius and Congresswoman Debbie Wasserman Schultz announced on January 10, 2014, in a blog, that, “today the Department of Health & Human Services (HHS) issued guidance to clarify that under the Affordable Care Act, most health insurance companies and employer plans must cover tamoxifen and raloxifene—like other recommended preventive services—without co-pays or other out of pocket expenses for women at increased risk for breast cancer.”¹

Related Article: Women’s health under the Affordable Care Act: What is covered? Lucia DiVenere, MA (September 2012)

This move by HHS comes in response to the US Preventive Services Task Force (USPSTF) recommendation in late September that clinicians offer prescription medications such as tamoxifen and raloxifene to women who are shown to be at a higher relative risk for breast cancer and at low risk for adverse medication effects.²

Related Article: USPSTF recommends tamoxifen or raloxifene to reduce breast cancer risk in high-risk patients (October 2013)

The US Food and Drug Administration (FDA) has approved tamoxifen as a chemo-preventive in at-risk women aged 35 years and older, and raloxifene for this same use in postmenopausal women. Both medications are selective estrogen receptor (ER) modulators that have been shown to reduce the incidence of invasive, ER-positive breast cancer.²

Related Article: What is the gynecologist’s role in the care of BRCA previvors? Robert L. Barbieri, MD (Editorial, September 2013)

The new ruling applies to those whose private insurance policies were written after the law was signed in 2010, as well as for women on Medicaid or Medicare.³

“Access to medications like tamoxifen or raloxifene is just one of many ways the Affordable Care Act is helping the fight against cancer,” write Sebelius and Schultz. “Through the Health Insurance Marketplace, the new health care law is also helping by making health care more affordable and accessible to millions of Americans. And when you consider that Americans who are uninsured and diagnosed with cancer are 60 percent more likely to die from that cancer than those who have insurance—the work that we do together to expand access to health insurance is work that saves lives.”¹

Health and Human Services Secretary Kathleen Sebelius and Congresswoman Debbie Wasserman Schultz announced on January 10, 2014, in a blog, that, “today the Department of Health & Human Services (HHS) issued guidance to clarify that under the Affordable Care Act, most health insurance companies and employer plans must cover tamoxifen and raloxifene—like other recommended preventive services—without co-pays or other out of pocket expenses for women at increased risk for breast cancer.”¹

Related Article: Women’s health under the Affordable Care Act: What is covered? Lucia DiVenere, MA (September 2012)

This move by HHS comes in response to the US Preventive Services Task Force (USPSTF) recommendation in late September that clinicians offer prescription medications such as tamoxifen and raloxifene to women who are shown to be at a higher relative risk for breast cancer and at low risk for adverse medication effects.²

Related Article: USPSTF recommends tamoxifen or raloxifene to reduce breast cancer risk in high-risk patients (October 2013)

The US Food and Drug Administration (FDA) has approved tamoxifen as a chemo-preventive in at-risk women aged 35 years and older, and raloxifene for this same use in postmenopausal women. Both medications are selective estrogen receptor (ER) modulators that have been shown to reduce the incidence of invasive, ER-positive breast cancer.²

Related Article: What is the gynecologist’s role in the care of BRCA previvors? Robert L. Barbieri, MD (Editorial, September 2013)

The new ruling applies to those whose private insurance policies were written after the law was signed in 2010, as well as for women on Medicaid or Medicare.³

“Access to medications like tamoxifen or raloxifene is just one of many ways the Affordable Care Act is helping the fight against cancer,” write Sebelius and Schultz. “Through the Health Insurance Marketplace, the new health care law is also helping by making health care more affordable and accessible to millions of Americans. And when you consider that Americans who are uninsured and diagnosed with cancer are 60 percent more likely to die from that cancer than those who have insurance—the work that we do together to expand access to health insurance is work that saves lives.”¹

Health and Human Services Secretary Kathleen Sebelius and Congresswoman Debbie Wasserman Schultz announced on January 10, 2014, in a blog, that, “today the Department of Health & Human Services (HHS) issued guidance to clarify that under the Affordable Care Act, most health insurance companies and employer plans must cover tamoxifen and raloxifene—like other recommended preventive services—without co-pays or other out of pocket expenses for women at increased risk for breast cancer.”¹

Related Article: Women’s health under the Affordable Care Act: What is covered? Lucia DiVenere, MA (September 2012)

This move by HHS comes in response to the US Preventive Services Task Force (USPSTF) recommendation in late September that clinicians offer prescription medications such as tamoxifen and raloxifene to women who are shown to be at a higher relative risk for breast cancer and at low risk for adverse medication effects.²

Related Article: USPSTF recommends tamoxifen or raloxifene to reduce breast cancer risk in high-risk patients (October 2013)

The US Food and Drug Administration (FDA) has approved tamoxifen as a chemo-preventive in at-risk women aged 35 years and older, and raloxifene for this same use in postmenopausal women. Both medications are selective estrogen receptor (ER) modulators that have been shown to reduce the incidence of invasive, ER-positive breast cancer.²

Related Article: What is the gynecologist’s role in the care of BRCA previvors? Robert L. Barbieri, MD (Editorial, September 2013)

The new ruling applies to those whose private insurance policies were written after the law was signed in 2010, as well as for women on Medicaid or Medicare.³

“Access to medications like tamoxifen or raloxifene is just one of many ways the Affordable Care Act is helping the fight against cancer,” write Sebelius and Schultz. “Through the Health Insurance Marketplace, the new health care law is also helping by making health care more affordable and accessible to millions of Americans. And when you consider that Americans who are uninsured and diagnosed with cancer are 60 percent more likely to die from that cancer than those who have insurance—the work that we do together to expand access to health insurance is work that saves lives.”¹

SAN ANTONIO – Extracorporeal shock wave therapy shows early promise for limiting the often-vexing problem of lymphedema arising after axillary lymphadenectomy.

In the first 10 affected patients treated in an ongoing randomized, sham-controlled clinical trial, lymphedema, as measured by median whole-arm water displacement, dropped from 4,200 mL at baseline by 192.5 mL after 10 once-weekly extracorporeal shock wave (ECSW) sessions. Patients who received sham sessions had a 12.5-mL decline from baseline measures, Dr. Sara Imboden reported at the San Antonio Breast Cancer Symposium.

Quantitative CT measures indicated the mean total cross-sectional area of the most swollen part of the arm decreased by 3% in the ECSW group, compared with 1.4% in the control group, added Dr. Imboden of the University of Bern (Switzerland).

A mean of 22 axillary lymph nodes had been removed from the breast cancer patients in the study. The ECSW therapy was performed over the length of the edematous arm at an energy density of 0.25-0.69 mJ/mm² once per week for 10 weeks. The control group followed the same treatment schedule, but the shock waves were contained inside the probe during their sessions.

None of the patients had to interrupt ECSW therapy due to complications.

The researchers plan to expand the randomized trial to include 30 patients, and to augment the results with patient reports of symptoms based on questionnaires assessing body image and with extended follow-up to evaluate functioning and recurrences.

The likely mechanism of benefit in patients with lymphedema involves ECSW-induced stimulation of angiogenesis and lymphatic vessel regeneration. These results have been demonstrated in animal studies.

No medications have been shown effective in treating lymphedema. Conventional therapy entails repeated manual lymph drainage and compression bandages.

Dr. Imboden reported having no financial conflicts of interest with regard to this university-funded study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Extracorporeal shock wave therapy shows early promise for limiting the often-vexing problem of lymphedema arising after axillary lymphadenectomy.

In the first 10 affected patients treated in an ongoing randomized, sham-controlled clinical trial, lymphedema, as measured by median whole-arm water displacement, dropped from 4,200 mL at baseline by 192.5 mL after 10 once-weekly extracorporeal shock wave (ECSW) sessions. Patients who received sham sessions had a 12.5-mL decline from baseline measures, Dr. Sara Imboden reported at the San Antonio Breast Cancer Symposium.

Quantitative CT measures indicated the mean total cross-sectional area of the most swollen part of the arm decreased by 3% in the ECSW group, compared with 1.4% in the control group, added Dr. Imboden of the University of Bern (Switzerland).

A mean of 22 axillary lymph nodes had been removed from the breast cancer patients in the study. The ECSW therapy was performed over the length of the edematous arm at an energy density of 0.25-0.69 mJ/mm² once per week for 10 weeks. The control group followed the same treatment schedule, but the shock waves were contained inside the probe during their sessions.

None of the patients had to interrupt ECSW therapy due to complications.

The researchers plan to expand the randomized trial to include 30 patients, and to augment the results with patient reports of symptoms based on questionnaires assessing body image and with extended follow-up to evaluate functioning and recurrences.

The likely mechanism of benefit in patients with lymphedema involves ECSW-induced stimulation of angiogenesis and lymphatic vessel regeneration. These results have been demonstrated in animal studies.

No medications have been shown effective in treating lymphedema. Conventional therapy entails repeated manual lymph drainage and compression bandages.

Dr. Imboden reported having no financial conflicts of interest with regard to this university-funded study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Extracorporeal shock wave therapy shows early promise for limiting the often-vexing problem of lymphedema arising after axillary lymphadenectomy.

In the first 10 affected patients treated in an ongoing randomized, sham-controlled clinical trial, lymphedema, as measured by median whole-arm water displacement, dropped from 4,200 mL at baseline by 192.5 mL after 10 once-weekly extracorporeal shock wave (ECSW) sessions. Patients who received sham sessions had a 12.5-mL decline from baseline measures, Dr. Sara Imboden reported at the San Antonio Breast Cancer Symposium.

Quantitative CT measures indicated the mean total cross-sectional area of the most swollen part of the arm decreased by 3% in the ECSW group, compared with 1.4% in the control group, added Dr. Imboden of the University of Bern (Switzerland).

A mean of 22 axillary lymph nodes had been removed from the breast cancer patients in the study. The ECSW therapy was performed over the length of the edematous arm at an energy density of 0.25-0.69 mJ/mm² once per week for 10 weeks. The control group followed the same treatment schedule, but the shock waves were contained inside the probe during their sessions.

None of the patients had to interrupt ECSW therapy due to complications.

The researchers plan to expand the randomized trial to include 30 patients, and to augment the results with patient reports of symptoms based on questionnaires assessing body image and with extended follow-up to evaluate functioning and recurrences.

The likely mechanism of benefit in patients with lymphedema involves ECSW-induced stimulation of angiogenesis and lymphatic vessel regeneration. These results have been demonstrated in animal studies.

No medications have been shown effective in treating lymphedema. Conventional therapy entails repeated manual lymph drainage and compression bandages.

Dr. Imboden reported having no financial conflicts of interest with regard to this university-funded study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Surgical removal of the primary tumor and affected lymph nodes afforded no overall survival benefit in women who had metastatic breast cancer at initial presentation, according to a pair of randomized trials presented at the San Antonio Breast Cancer Symposium.

In a first trial, conducted among 350 women in India who had responded to initial chemotherapy, about 20% of the women were still alive at 5 years regardless of whether they had surgery or just received more systemic therapy, first author Dr. Rajendra Badwe, director of the Tata Memorial Hospital in Mumbai, India, reported in a session and at a press briefing.

Superior locoregional control conferred by surgery was canceled out by a higher risk of progression in distant sites, lending support to more than 20-year-old preclinical data by Dr. Bernard Fisher and his colleagues suggesting that an intact primary suppresses growth of distant metastases (Cancer Res. 1989;49:1996-2001).

"Locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit and hence should not be offered as a routine practice," Dr. Badwe commented.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases. ... This is the first time that we have evidence in human studies that locoregional treatment has a great kinetic effect on distant metastases," he added.

In a second trial, conducted among 293 women in Turkey with untreated de novo metastatic breast cancer, median estimated survival was statistically indistinguishable, at about 3.5 years, regardless of whether women had up-front surgery or simply systemic therapy, first author Dr. Atilla Soran reported in a session on behalf of the Turkish Federation of Societies for Breast Diseases.

Subgroup analyses suggested that surgery conferred a survival advantage among women with solitary bone metastases but a survival disadvantage among women with multiple liver or lung metastases.

The rate of locoregional progression was one-fifth as high with surgery as with systemic therapy.

"There was no statistically significant difference in overall survival at early follow-up, but we need longer follow-up," Dr. Soran commented. "There were potentially important subgroup differences."

The two trials have implications – both for other ongoing trials and for patient care – according to invited discussant Dr. Seema A. Khan, a professor of surgery and Bluhm Family Professor of Cancer Research at Northwestern University, Chicago, and a physician at the university’s Lynn Sage Breast Center.

"A large benefit of primary site local therapy seems unlikely based on the data we saw today," she maintained. "The assumptions we have used in our ongoing trial designs will need to be reassessed. Preplanned pooled analyses may yield sufficient power to detect smaller differences."

As for patient care, "it is pretty clear that at this point in time, we have to make sure that our patients understand that there is really no proven survival advantage to primary site local therapy," Dr. Khan said. "So I don’t think this treatment should be offered to patients with asymptomatic tumors unless they are participating in a clinical trial. There may be a local control advantage; we need to see more data on that."

Indian trial

Participants in the Indian trial, conducted between 2005 and 2013, were women with de novo metastatic breast cancer who had had a complete or partial response to anthracycline chemotherapy alone or with a taxane.

They were randomized evenly to receive locoregional therapy (lumpectomy or mastectomy with axillary lymph node dissection, plus radiation therapy to the chest wall or breast and lymph nodes) or no locoregional therapy as a control. Both groups received hormonal therapy if indicated.

In the control group, about 10% of women underwent a palliative mastectomy because of impending fungation or pain in the breast, as permitted by study protocol, according to Dr. Badwe.

The patients thus received contemporary therapy, he said, except that the 16% with HER2-positive disease did not receive the targeted agent trastuzumab (Herceptin).

Results showed that median overall survival was about 18 months, and the 5-year rate was 19.2% with locoregional therapy and 20.5% without it, a nonsignificant difference. "Uniformly, there was no difference at all in any subsets," Dr. Badwe reported.

The study had a one-sided superiority design, he noted. "We wouldn’t have been able to see a 2.5- or 3-month difference, or a 4% detriment" in overall survival.

The surgery group had a lower risk of local progression-free survival events (hazard ratio, 0.16; P = .00), but a higher risk of distant progression-free survival events (HR, 1.42; P = .01).

Several theories might explain why removal of the primary would accelerate growth of metastases, according to Dr. Badwe.

"The first and the foremost is that the act of surgery itself might elaborate some growth factors which might allow metastatic disease to grow. The second possibility, which was suggested by Dr. Fisher (Cancer Res. 1989;49:1996-2001) is that the primary tumor, which predates the onset of distant metastases, elaborates some inhibitory factors, and they are not there once the primary tumor is removed, bestowing autonomy of growth on the distant metastases," he explained. "And the third possibility is the act of surgery might induce some more metastatic processes by dissemination and create new disease."

Session attendee Dr. Steven Vogl, an oncologist in the Bronx, N.Y., said, "The ascertainment of disease progression requires disease that you can follow. A woman with bone-only metastases with her cancer in place, you can tell when her cancer is getting worse because the primary site or the axillary nodes are getting bigger. It’s much more difficult if you’ve taken those off and irradiated the chest wall. Have you looked at your data to see if that’s what was going on, why you had more distant metastases, because they couldn’t progress locally? This is a medical trial explanation that contradicts Fisher’s biologic hypothesis."

"There was a fixed time duration at which systemic investigations were performed to assess whether the distant metastases progressed," Dr. Badwe replied. If anything, the patients who did not have surgery had more assessments of their distant metastases, he said.

Dr. Tari A. King, a session attendee from the Memorial Sloan-Kettering Cancer Center, New York, noted that a lack of HER2 therapy in the trial may have had a large effect.

"We do have prospective registry data here [abstract 18-09, presented in a poster session] from a trial that we completed in the United States sponsored by the Translational Breast Cancer Research Consortium, and the patients in our study, whether they received surgery or not, their 2-year overall survival is far superior to what you’ve just showed us," she commented. "So I’m not sure that we can really apply your data to the modern targeted therapy regimens that we see in the United States."

Turkish trial

The Turkish trial, known as the MF07-01 trial, was conduced between 2008 and 2012 among treatment-naïve patients.

They were randomized evenly to receive either systemic therapy alone or surgery for the primary tumor (with or without axillary dissection) followed by radiation therapy if indicated, plus systemic therapy.

All patients received hormonal therapy as needed, and those with HER2-positive disease received trastuzumab.

With a median follow-up of 18 months, the median overall survival was 46 months with initial surgery and 42 months with initial systemic therapy, a nonsignificant difference, reported Dr. Soran, who disclosed no relevant conflicts of interest.

In unplanned subgroup analyses, the findings were similar for most subgroups of patients. However, surgery yielded superior survival in patients with solitary bone metastases (not reached vs. 42 months, P = .02) and inferior survival in patients having multiple liver or pulmonary metastases (16 months vs. not reached, P = .02).

The rate of locoregional progression was much lower with initial surgery than with initial systemic therapy (0.7% vs. 3.6%).

Dr. Soran emphasized that the trial’s planned median follow-up is 36 months, so the presented results are only preliminary. Quality of life and morbidity analyses are ongoing.

Dr. Badwe and Dr. Soran disclosed no relevant conflicts of interest.

SAN ANTONIO – Surgical removal of the primary tumor and affected lymph nodes afforded no overall survival benefit in women who had metastatic breast cancer at initial presentation, according to a pair of randomized trials presented at the San Antonio Breast Cancer Symposium.

In a first trial, conducted among 350 women in India who had responded to initial chemotherapy, about 20% of the women were still alive at 5 years regardless of whether they had surgery or just received more systemic therapy, first author Dr. Rajendra Badwe, director of the Tata Memorial Hospital in Mumbai, India, reported in a session and at a press briefing.

Superior locoregional control conferred by surgery was canceled out by a higher risk of progression in distant sites, lending support to more than 20-year-old preclinical data by Dr. Bernard Fisher and his colleagues suggesting that an intact primary suppresses growth of distant metastases (Cancer Res. 1989;49:1996-2001).

"Locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit and hence should not be offered as a routine practice," Dr. Badwe commented.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases. ... This is the first time that we have evidence in human studies that locoregional treatment has a great kinetic effect on distant metastases," he added.

In a second trial, conducted among 293 women in Turkey with untreated de novo metastatic breast cancer, median estimated survival was statistically indistinguishable, at about 3.5 years, regardless of whether women had up-front surgery or simply systemic therapy, first author Dr. Atilla Soran reported in a session on behalf of the Turkish Federation of Societies for Breast Diseases.

Subgroup analyses suggested that surgery conferred a survival advantage among women with solitary bone metastases but a survival disadvantage among women with multiple liver or lung metastases.

The rate of locoregional progression was one-fifth as high with surgery as with systemic therapy.

"There was no statistically significant difference in overall survival at early follow-up, but we need longer follow-up," Dr. Soran commented. "There were potentially important subgroup differences."

The two trials have implications – both for other ongoing trials and for patient care – according to invited discussant Dr. Seema A. Khan, a professor of surgery and Bluhm Family Professor of Cancer Research at Northwestern University, Chicago, and a physician at the university’s Lynn Sage Breast Center.

"A large benefit of primary site local therapy seems unlikely based on the data we saw today," she maintained. "The assumptions we have used in our ongoing trial designs will need to be reassessed. Preplanned pooled analyses may yield sufficient power to detect smaller differences."

As for patient care, "it is pretty clear that at this point in time, we have to make sure that our patients understand that there is really no proven survival advantage to primary site local therapy," Dr. Khan said. "So I don’t think this treatment should be offered to patients with asymptomatic tumors unless they are participating in a clinical trial. There may be a local control advantage; we need to see more data on that."

Indian trial

Participants in the Indian trial, conducted between 2005 and 2013, were women with de novo metastatic breast cancer who had had a complete or partial response to anthracycline chemotherapy alone or with a taxane.

They were randomized evenly to receive locoregional therapy (lumpectomy or mastectomy with axillary lymph node dissection, plus radiation therapy to the chest wall or breast and lymph nodes) or no locoregional therapy as a control. Both groups received hormonal therapy if indicated.

In the control group, about 10% of women underwent a palliative mastectomy because of impending fungation or pain in the breast, as permitted by study protocol, according to Dr. Badwe.

The patients thus received contemporary therapy, he said, except that the 16% with HER2-positive disease did not receive the targeted agent trastuzumab (Herceptin).

Results showed that median overall survival was about 18 months, and the 5-year rate was 19.2% with locoregional therapy and 20.5% without it, a nonsignificant difference. "Uniformly, there was no difference at all in any subsets," Dr. Badwe reported.

The study had a one-sided superiority design, he noted. "We wouldn’t have been able to see a 2.5- or 3-month difference, or a 4% detriment" in overall survival.

The surgery group had a lower risk of local progression-free survival events (hazard ratio, 0.16; P = .00), but a higher risk of distant progression-free survival events (HR, 1.42; P = .01).

Several theories might explain why removal of the primary would accelerate growth of metastases, according to Dr. Badwe.

"The first and the foremost is that the act of surgery itself might elaborate some growth factors which might allow metastatic disease to grow. The second possibility, which was suggested by Dr. Fisher (Cancer Res. 1989;49:1996-2001) is that the primary tumor, which predates the onset of distant metastases, elaborates some inhibitory factors, and they are not there once the primary tumor is removed, bestowing autonomy of growth on the distant metastases," he explained. "And the third possibility is the act of surgery might induce some more metastatic processes by dissemination and create new disease."

Session attendee Dr. Steven Vogl, an oncologist in the Bronx, N.Y., said, "The ascertainment of disease progression requires disease that you can follow. A woman with bone-only metastases with her cancer in place, you can tell when her cancer is getting worse because the primary site or the axillary nodes are getting bigger. It’s much more difficult if you’ve taken those off and irradiated the chest wall. Have you looked at your data to see if that’s what was going on, why you had more distant metastases, because they couldn’t progress locally? This is a medical trial explanation that contradicts Fisher’s biologic hypothesis."

"There was a fixed time duration at which systemic investigations were performed to assess whether the distant metastases progressed," Dr. Badwe replied. If anything, the patients who did not have surgery had more assessments of their distant metastases, he said.

Dr. Tari A. King, a session attendee from the Memorial Sloan-Kettering Cancer Center, New York, noted that a lack of HER2 therapy in the trial may have had a large effect.

"We do have prospective registry data here [abstract 18-09, presented in a poster session] from a trial that we completed in the United States sponsored by the Translational Breast Cancer Research Consortium, and the patients in our study, whether they received surgery or not, their 2-year overall survival is far superior to what you’ve just showed us," she commented. "So I’m not sure that we can really apply your data to the modern targeted therapy regimens that we see in the United States."

Turkish trial

The Turkish trial, known as the MF07-01 trial, was conduced between 2008 and 2012 among treatment-naïve patients.

They were randomized evenly to receive either systemic therapy alone or surgery for the primary tumor (with or without axillary dissection) followed by radiation therapy if indicated, plus systemic therapy.

All patients received hormonal therapy as needed, and those with HER2-positive disease received trastuzumab.

With a median follow-up of 18 months, the median overall survival was 46 months with initial surgery and 42 months with initial systemic therapy, a nonsignificant difference, reported Dr. Soran, who disclosed no relevant conflicts of interest.

In unplanned subgroup analyses, the findings were similar for most subgroups of patients. However, surgery yielded superior survival in patients with solitary bone metastases (not reached vs. 42 months, P = .02) and inferior survival in patients having multiple liver or pulmonary metastases (16 months vs. not reached, P = .02).

The rate of locoregional progression was much lower with initial surgery than with initial systemic therapy (0.7% vs. 3.6%).

Dr. Soran emphasized that the trial’s planned median follow-up is 36 months, so the presented results are only preliminary. Quality of life and morbidity analyses are ongoing.

Dr. Badwe and Dr. Soran disclosed no relevant conflicts of interest.

SAN ANTONIO – Surgical removal of the primary tumor and affected lymph nodes afforded no overall survival benefit in women who had metastatic breast cancer at initial presentation, according to a pair of randomized trials presented at the San Antonio Breast Cancer Symposium.

In a first trial, conducted among 350 women in India who had responded to initial chemotherapy, about 20% of the women were still alive at 5 years regardless of whether they had surgery or just received more systemic therapy, first author Dr. Rajendra Badwe, director of the Tata Memorial Hospital in Mumbai, India, reported in a session and at a press briefing.

Superior locoregional control conferred by surgery was canceled out by a higher risk of progression in distant sites, lending support to more than 20-year-old preclinical data by Dr. Bernard Fisher and his colleagues suggesting that an intact primary suppresses growth of distant metastases (Cancer Res. 1989;49:1996-2001).

"Locoregional treatment of the primary tumor in women presenting with metastatic breast cancer did not result in any overall survival benefit and hence should not be offered as a routine practice," Dr. Badwe commented.

"The biological fallout of this study is that surgical removal of the primary tumor in these women appears to confer a growth advantage on distant metastases. ... This is the first time that we have evidence in human studies that locoregional treatment has a great kinetic effect on distant metastases," he added.

In a second trial, conducted among 293 women in Turkey with untreated de novo metastatic breast cancer, median estimated survival was statistically indistinguishable, at about 3.5 years, regardless of whether women had up-front surgery or simply systemic therapy, first author Dr. Atilla Soran reported in a session on behalf of the Turkish Federation of Societies for Breast Diseases.

Subgroup analyses suggested that surgery conferred a survival advantage among women with solitary bone metastases but a survival disadvantage among women with multiple liver or lung metastases.

The rate of locoregional progression was one-fifth as high with surgery as with systemic therapy.

"There was no statistically significant difference in overall survival at early follow-up, but we need longer follow-up," Dr. Soran commented. "There were potentially important subgroup differences."

The two trials have implications – both for other ongoing trials and for patient care – according to invited discussant Dr. Seema A. Khan, a professor of surgery and Bluhm Family Professor of Cancer Research at Northwestern University, Chicago, and a physician at the university’s Lynn Sage Breast Center.

"A large benefit of primary site local therapy seems unlikely based on the data we saw today," she maintained. "The assumptions we have used in our ongoing trial designs will need to be reassessed. Preplanned pooled analyses may yield sufficient power to detect smaller differences."

As for patient care, "it is pretty clear that at this point in time, we have to make sure that our patients understand that there is really no proven survival advantage to primary site local therapy," Dr. Khan said. "So I don’t think this treatment should be offered to patients with asymptomatic tumors unless they are participating in a clinical trial. There may be a local control advantage; we need to see more data on that."

Indian trial

Participants in the Indian trial, conducted between 2005 and 2013, were women with de novo metastatic breast cancer who had had a complete or partial response to anthracycline chemotherapy alone or with a taxane.

They were randomized evenly to receive locoregional therapy (lumpectomy or mastectomy with axillary lymph node dissection, plus radiation therapy to the chest wall or breast and lymph nodes) or no locoregional therapy as a control. Both groups received hormonal therapy if indicated.

In the control group, about 10% of women underwent a palliative mastectomy because of impending fungation or pain in the breast, as permitted by study protocol, according to Dr. Badwe.

The patients thus received contemporary therapy, he said, except that the 16% with HER2-positive disease did not receive the targeted agent trastuzumab (Herceptin).

Results showed that median overall survival was about 18 months, and the 5-year rate was 19.2% with locoregional therapy and 20.5% without it, a nonsignificant difference. "Uniformly, there was no difference at all in any subsets," Dr. Badwe reported.

The study had a one-sided superiority design, he noted. "We wouldn’t have been able to see a 2.5- or 3-month difference, or a 4% detriment" in overall survival.

The surgery group had a lower risk of local progression-free survival events (hazard ratio, 0.16; P = .00), but a higher risk of distant progression-free survival events (HR, 1.42; P = .01).

Several theories might explain why removal of the primary would accelerate growth of metastases, according to Dr. Badwe.

"The first and the foremost is that the act of surgery itself might elaborate some growth factors which might allow metastatic disease to grow. The second possibility, which was suggested by Dr. Fisher (Cancer Res. 1989;49:1996-2001) is that the primary tumor, which predates the onset of distant metastases, elaborates some inhibitory factors, and they are not there once the primary tumor is removed, bestowing autonomy of growth on the distant metastases," he explained. "And the third possibility is the act of surgery might induce some more metastatic processes by dissemination and create new disease."

Session attendee Dr. Steven Vogl, an oncologist in the Bronx, N.Y., said, "The ascertainment of disease progression requires disease that you can follow. A woman with bone-only metastases with her cancer in place, you can tell when her cancer is getting worse because the primary site or the axillary nodes are getting bigger. It’s much more difficult if you’ve taken those off and irradiated the chest wall. Have you looked at your data to see if that’s what was going on, why you had more distant metastases, because they couldn’t progress locally? This is a medical trial explanation that contradicts Fisher’s biologic hypothesis."

"There was a fixed time duration at which systemic investigations were performed to assess whether the distant metastases progressed," Dr. Badwe replied. If anything, the patients who did not have surgery had more assessments of their distant metastases, he said.

Dr. Tari A. King, a session attendee from the Memorial Sloan-Kettering Cancer Center, New York, noted that a lack of HER2 therapy in the trial may have had a large effect.

"We do have prospective registry data here [abstract 18-09, presented in a poster session] from a trial that we completed in the United States sponsored by the Translational Breast Cancer Research Consortium, and the patients in our study, whether they received surgery or not, their 2-year overall survival is far superior to what you’ve just showed us," she commented. "So I’m not sure that we can really apply your data to the modern targeted therapy regimens that we see in the United States."

Turkish trial

The Turkish trial, known as the MF07-01 trial, was conduced between 2008 and 2012 among treatment-naïve patients.

They were randomized evenly to receive either systemic therapy alone or surgery for the primary tumor (with or without axillary dissection) followed by radiation therapy if indicated, plus systemic therapy.

All patients received hormonal therapy as needed, and those with HER2-positive disease received trastuzumab.

With a median follow-up of 18 months, the median overall survival was 46 months with initial surgery and 42 months with initial systemic therapy, a nonsignificant difference, reported Dr. Soran, who disclosed no relevant conflicts of interest.

In unplanned subgroup analyses, the findings were similar for most subgroups of patients. However, surgery yielded superior survival in patients with solitary bone metastases (not reached vs. 42 months, P = .02) and inferior survival in patients having multiple liver or pulmonary metastases (16 months vs. not reached, P = .02).

The rate of locoregional progression was much lower with initial surgery than with initial systemic therapy (0.7% vs. 3.6%).

Dr. Soran emphasized that the trial’s planned median follow-up is 36 months, so the presented results are only preliminary. Quality of life and morbidity analyses are ongoing.

Dr. Badwe and Dr. Soran disclosed no relevant conflicts of interest.

SAN ANTONIO – Adjuvant zoledronate failed to improve outcomes in breast cancer patients with residual tumor following neoadjuvant chemotherapy in a large, randomized, phase-3 trial, Dr. Gunter von Minckwitz reported at the San Antonio Breast Cancer Symposium.

There was, however, a bright spot buried within the results of the Neo-Adjuvant Trial Add-On (NATAN) trial: the subset of participants over age 55 years showed a 17% improvement in disease-free survival compared with controls. Although this difference didn’t reach statistical significance because of limited patient numbers, it was closely similar to the benefit seen for adjuvant bisphosphonate therapy in the Early Breast Cancer Trialists Collaborative Group’s practice-changing meta-analysis presented earlier at the San Antonio symposium.

That meta-analysis, presented by Dr. Robert Coleman of the University of Sheffield (England), included more than 17,000 participants in randomized trials. The conclusion was that adjuvant bisphosphonate therapy was of significant benefit in postmenopausal breast cancer patients, with a 17% reduction in the risk of mortality and a 34% decrease in the risk of bone metastases, compared with controls. Premenopausal patients didn’t benefit from adjuvant bisphosphonate therapy.

"We had discussed doing another bisphosphonate trial, this one to be limited to postmenopausal patients without a pathologic complete response after neoadjuvant chemotherapy, but having seen Robert Coleman’s presentation yesterday we are not very much in favor of that any longer. We have our practice guideline meeting for Germany in January, and I expect that we will give a recommendation to use bisphosphonates in postmenopausal patients, so it makes no sense to do another prospective trial," said Dr. von Minckwitz, chairman of the German Breast Group, Neu-Isenburg, and a gynecologist at the University of Frankfurt.

NATAN was carried out because patients with residual disease after neoadjuvant chemotherapy have a worse prognosis than those with a pathologic complete response, and they have few adjuvant treatment options. The study included 654 patients with residual disease after at least four cycles of neoadjuvant anthracycline/taxane-based chemotherapy. Patients were randomized to a planned 5 years of postsurgical intravenous zoledronate or observation, plus adjuvant endocrine therapy and/or trastuzumab as indicated.

The study was halted early due to futility after a median follow-up of 48 months because of virtually identical event-free survival rates in the two study arms. Women over age 55 years, who comprised one-third of the study population, were the only subgroup with a strong, albeit nonsignificant, trend toward benefit for zoledronate.

There is a clear need for new treatment options for women with residual tumor after neoadjuvant chemotherapy, particularly those who aren’t postmenopausal. Several novel agents are now in clinical trials in patients with chemoresistant breast cancer, including rucaparib, an oral small-molecule inhibitor of PARP (poly ADP-ribose polymerase), for triple-negative breast cancer; palbociclib, an oral and selective inhibitor of cyclin dependent kinases 4 and 6, in women with hormone receptor–positive/HER2-negative disease; and trastuzumab emtansine, a conjugate of trastuzumab and the cytotoxic agent mertansine, in patients with chemoresistant HER2-positive breast cancer, Dr. von Minckwitz said.

NATAN was funded by Novartis. Dr. von Minckwitz reported having received research grants from, and serving as a speaker and consultant for, Novartis and Roche.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adjuvant zoledronate failed to improve outcomes in breast cancer patients with residual tumor following neoadjuvant chemotherapy in a large, randomized, phase-3 trial, Dr. Gunter von Minckwitz reported at the San Antonio Breast Cancer Symposium.

There was, however, a bright spot buried within the results of the Neo-Adjuvant Trial Add-On (NATAN) trial: the subset of participants over age 55 years showed a 17% improvement in disease-free survival compared with controls. Although this difference didn’t reach statistical significance because of limited patient numbers, it was closely similar to the benefit seen for adjuvant bisphosphonate therapy in the Early Breast Cancer Trialists Collaborative Group’s practice-changing meta-analysis presented earlier at the San Antonio symposium.

That meta-analysis, presented by Dr. Robert Coleman of the University of Sheffield (England), included more than 17,000 participants in randomized trials. The conclusion was that adjuvant bisphosphonate therapy was of significant benefit in postmenopausal breast cancer patients, with a 17% reduction in the risk of mortality and a 34% decrease in the risk of bone metastases, compared with controls. Premenopausal patients didn’t benefit from adjuvant bisphosphonate therapy.

"We had discussed doing another bisphosphonate trial, this one to be limited to postmenopausal patients without a pathologic complete response after neoadjuvant chemotherapy, but having seen Robert Coleman’s presentation yesterday we are not very much in favor of that any longer. We have our practice guideline meeting for Germany in January, and I expect that we will give a recommendation to use bisphosphonates in postmenopausal patients, so it makes no sense to do another prospective trial," said Dr. von Minckwitz, chairman of the German Breast Group, Neu-Isenburg, and a gynecologist at the University of Frankfurt.

NATAN was carried out because patients with residual disease after neoadjuvant chemotherapy have a worse prognosis than those with a pathologic complete response, and they have few adjuvant treatment options. The study included 654 patients with residual disease after at least four cycles of neoadjuvant anthracycline/taxane-based chemotherapy. Patients were randomized to a planned 5 years of postsurgical intravenous zoledronate or observation, plus adjuvant endocrine therapy and/or trastuzumab as indicated.

The study was halted early due to futility after a median follow-up of 48 months because of virtually identical event-free survival rates in the two study arms. Women over age 55 years, who comprised one-third of the study population, were the only subgroup with a strong, albeit nonsignificant, trend toward benefit for zoledronate.

There is a clear need for new treatment options for women with residual tumor after neoadjuvant chemotherapy, particularly those who aren’t postmenopausal. Several novel agents are now in clinical trials in patients with chemoresistant breast cancer, including rucaparib, an oral small-molecule inhibitor of PARP (poly ADP-ribose polymerase), for triple-negative breast cancer; palbociclib, an oral and selective inhibitor of cyclin dependent kinases 4 and 6, in women with hormone receptor–positive/HER2-negative disease; and trastuzumab emtansine, a conjugate of trastuzumab and the cytotoxic agent mertansine, in patients with chemoresistant HER2-positive breast cancer, Dr. von Minckwitz said.

NATAN was funded by Novartis. Dr. von Minckwitz reported having received research grants from, and serving as a speaker and consultant for, Novartis and Roche.

bjancin@frontlinemedcom.com

SAN ANTONIO – Adjuvant zoledronate failed to improve outcomes in breast cancer patients with residual tumor following neoadjuvant chemotherapy in a large, randomized, phase-3 trial, Dr. Gunter von Minckwitz reported at the San Antonio Breast Cancer Symposium.

There was, however, a bright spot buried within the results of the Neo-Adjuvant Trial Add-On (NATAN) trial: the subset of participants over age 55 years showed a 17% improvement in disease-free survival compared with controls. Although this difference didn’t reach statistical significance because of limited patient numbers, it was closely similar to the benefit seen for adjuvant bisphosphonate therapy in the Early Breast Cancer Trialists Collaborative Group’s practice-changing meta-analysis presented earlier at the San Antonio symposium.

That meta-analysis, presented by Dr. Robert Coleman of the University of Sheffield (England), included more than 17,000 participants in randomized trials. The conclusion was that adjuvant bisphosphonate therapy was of significant benefit in postmenopausal breast cancer patients, with a 17% reduction in the risk of mortality and a 34% decrease in the risk of bone metastases, compared with controls. Premenopausal patients didn’t benefit from adjuvant bisphosphonate therapy.

"We had discussed doing another bisphosphonate trial, this one to be limited to postmenopausal patients without a pathologic complete response after neoadjuvant chemotherapy, but having seen Robert Coleman’s presentation yesterday we are not very much in favor of that any longer. We have our practice guideline meeting for Germany in January, and I expect that we will give a recommendation to use bisphosphonates in postmenopausal patients, so it makes no sense to do another prospective trial," said Dr. von Minckwitz, chairman of the German Breast Group, Neu-Isenburg, and a gynecologist at the University of Frankfurt.

NATAN was carried out because patients with residual disease after neoadjuvant chemotherapy have a worse prognosis than those with a pathologic complete response, and they have few adjuvant treatment options. The study included 654 patients with residual disease after at least four cycles of neoadjuvant anthracycline/taxane-based chemotherapy. Patients were randomized to a planned 5 years of postsurgical intravenous zoledronate or observation, plus adjuvant endocrine therapy and/or trastuzumab as indicated.

The study was halted early due to futility after a median follow-up of 48 months because of virtually identical event-free survival rates in the two study arms. Women over age 55 years, who comprised one-third of the study population, were the only subgroup with a strong, albeit nonsignificant, trend toward benefit for zoledronate.

There is a clear need for new treatment options for women with residual tumor after neoadjuvant chemotherapy, particularly those who aren’t postmenopausal. Several novel agents are now in clinical trials in patients with chemoresistant breast cancer, including rucaparib, an oral small-molecule inhibitor of PARP (poly ADP-ribose polymerase), for triple-negative breast cancer; palbociclib, an oral and selective inhibitor of cyclin dependent kinases 4 and 6, in women with hormone receptor–positive/HER2-negative disease; and trastuzumab emtansine, a conjugate of trastuzumab and the cytotoxic agent mertansine, in patients with chemoresistant HER2-positive breast cancer, Dr. von Minckwitz said.

NATAN was funded by Novartis. Dr. von Minckwitz reported having received research grants from, and serving as a speaker and consultant for, Novartis and Roche.

bjancin@frontlinemedcom.com

SAN ANTONIO – Perineural injection of bupivacaine and dexamethasone was a simple and effective treatment for chronic neuropathic pain following mastectomy, based on results of a pilot study.

The effectiveness of this novel therapy strongly suggests the source of this common pain syndrome is damage to the T4 and T5 sensory nerves during surgery, rather than damage to the intercostobrachial nerve, as traditionally thought, according to Dr. Cathy J. Tang of the University of California, San Francisco.

The T4 and T5 sensory nerves come off the chest wall and enter the breast accompanied by a blood vessel. When these nerves are cut and cauterized during mastectomy, the resultant nerve damage can manifest as neuroma formation and neuropathic pain along the two dermatomes, she said at the San Antonio Breast Cancer Symposium.

Chronic postmastectomy breast pain is commonly referred to as postmastectomy pain syndrome. Published estimates of its incidence after mastectomy range from 20% to 68%. The pain can start in the immediate postoperative period, or onset can be delayed up to 6 months or more post mastectomy. The pain is typically experienced as a shooting or burning pain, with point tenderness. It persists well after the expected healing period.

The intervention involves identifying a patient’s points of maximum pain or tenderness, usually located laterally along the midaxillary line or at the inframammary fold directly below the nipple. These points are injected at the level of the chest wall. Each injection consists of 2 mL of an equal ratio of 0.5% bupivacaine plus 4 mg/mL of dexamethasone followed by a minute or two of massage to enhance infiltration of the area.

Dr. Tang reported on 19 patients who developed postmastectomy pain syndrome after either partial mastectomy, total mastectomy with immediate reconstruction, or lateral core biopsy in one case. A total of 29 points of maximum tenderness were identified and treated. All patients had pain relief within minutes, with point pain scores on a 0-10 scale falling from 8-9 to 0-1. Long-term pain relief was experienced after 17 of the 29 initial injections (59%) in 11 patients. Pain was resolved at another nine sites after a second injection. A third injection at one recalcitrant site led to long-term pain relief. Thus, perineural injections alleviated pain at 27 of 29 treated sites, or 93%, at a mean of 10.7 months of follow-up.

In light of how simple and safe this treatment is, Dr. Tang urged routine inquiry about postmastectomy neuropathic pain. Patients with postmastectomy pain often report an inability to lie on the affected side or to wear a bra.

The study also indicates the importance of careful dissection of the T4 and T5 sensory nerves during mastectomy in order to minimize the risk of postoperative neuroma formation.

Dr. Tang reported having no financial conflicts regarding this unfunded study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Perineural injection of bupivacaine and dexamethasone was a simple and effective treatment for chronic neuropathic pain following mastectomy, based on results of a pilot study.

The effectiveness of this novel therapy strongly suggests the source of this common pain syndrome is damage to the T4 and T5 sensory nerves during surgery, rather than damage to the intercostobrachial nerve, as traditionally thought, according to Dr. Cathy J. Tang of the University of California, San Francisco.

The T4 and T5 sensory nerves come off the chest wall and enter the breast accompanied by a blood vessel. When these nerves are cut and cauterized during mastectomy, the resultant nerve damage can manifest as neuroma formation and neuropathic pain along the two dermatomes, she said at the San Antonio Breast Cancer Symposium.

Chronic postmastectomy breast pain is commonly referred to as postmastectomy pain syndrome. Published estimates of its incidence after mastectomy range from 20% to 68%. The pain can start in the immediate postoperative period, or onset can be delayed up to 6 months or more post mastectomy. The pain is typically experienced as a shooting or burning pain, with point tenderness. It persists well after the expected healing period.

The intervention involves identifying a patient’s points of maximum pain or tenderness, usually located laterally along the midaxillary line or at the inframammary fold directly below the nipple. These points are injected at the level of the chest wall. Each injection consists of 2 mL of an equal ratio of 0.5% bupivacaine plus 4 mg/mL of dexamethasone followed by a minute or two of massage to enhance infiltration of the area.

Dr. Tang reported on 19 patients who developed postmastectomy pain syndrome after either partial mastectomy, total mastectomy with immediate reconstruction, or lateral core biopsy in one case. A total of 29 points of maximum tenderness were identified and treated. All patients had pain relief within minutes, with point pain scores on a 0-10 scale falling from 8-9 to 0-1. Long-term pain relief was experienced after 17 of the 29 initial injections (59%) in 11 patients. Pain was resolved at another nine sites after a second injection. A third injection at one recalcitrant site led to long-term pain relief. Thus, perineural injections alleviated pain at 27 of 29 treated sites, or 93%, at a mean of 10.7 months of follow-up.

In light of how simple and safe this treatment is, Dr. Tang urged routine inquiry about postmastectomy neuropathic pain. Patients with postmastectomy pain often report an inability to lie on the affected side or to wear a bra.

The study also indicates the importance of careful dissection of the T4 and T5 sensory nerves during mastectomy in order to minimize the risk of postoperative neuroma formation.

Dr. Tang reported having no financial conflicts regarding this unfunded study.

bjancin@frontlinemedcom.com

SAN ANTONIO – Perineural injection of bupivacaine and dexamethasone was a simple and effective treatment for chronic neuropathic pain following mastectomy, based on results of a pilot study.

The effectiveness of this novel therapy strongly suggests the source of this common pain syndrome is damage to the T4 and T5 sensory nerves during surgery, rather than damage to the intercostobrachial nerve, as traditionally thought, according to Dr. Cathy J. Tang of the University of California, San Francisco.

The T4 and T5 sensory nerves come off the chest wall and enter the breast accompanied by a blood vessel. When these nerves are cut and cauterized during mastectomy, the resultant nerve damage can manifest as neuroma formation and neuropathic pain along the two dermatomes, she said at the San Antonio Breast Cancer Symposium.

Chronic postmastectomy breast pain is commonly referred to as postmastectomy pain syndrome. Published estimates of its incidence after mastectomy range from 20% to 68%. The pain can start in the immediate postoperative period, or onset can be delayed up to 6 months or more post mastectomy. The pain is typically experienced as a shooting or burning pain, with point tenderness. It persists well after the expected healing period.

The intervention involves identifying a patient’s points of maximum pain or tenderness, usually located laterally along the midaxillary line or at the inframammary fold directly below the nipple. These points are injected at the level of the chest wall. Each injection consists of 2 mL of an equal ratio of 0.5% bupivacaine plus 4 mg/mL of dexamethasone followed by a minute or two of massage to enhance infiltration of the area.

Dr. Tang reported on 19 patients who developed postmastectomy pain syndrome after either partial mastectomy, total mastectomy with immediate reconstruction, or lateral core biopsy in one case. A total of 29 points of maximum tenderness were identified and treated. All patients had pain relief within minutes, with point pain scores on a 0-10 scale falling from 8-9 to 0-1. Long-term pain relief was experienced after 17 of the 29 initial injections (59%) in 11 patients. Pain was resolved at another nine sites after a second injection. A third injection at one recalcitrant site led to long-term pain relief. Thus, perineural injections alleviated pain at 27 of 29 treated sites, or 93%, at a mean of 10.7 months of follow-up.

In light of how simple and safe this treatment is, Dr. Tang urged routine inquiry about postmastectomy neuropathic pain. Patients with postmastectomy pain often report an inability to lie on the affected side or to wear a bra.

The study also indicates the importance of careful dissection of the T4 and T5 sensory nerves during mastectomy in order to minimize the risk of postoperative neuroma formation.

Dr. Tang reported having no financial conflicts regarding this unfunded study.

bjancin@frontlinemedcom.com

Asymptomatic women with a family history of breast, ovarian, tubal, or peritoneal cancers should be screened for potentially increased risk for BRCA mutations, according to a new guideline from the U.S. Preventive Services Task Force.

Those with positive screening results should undergo genetic counseling to determine whether they should be tested for mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, according to the guideline, which was published online Dec. 23 in Annals of Internal Medicine. The guideline applies only to at-risk women who have not been previously diagnosed with BRCA-related cancer and who have no signs or symptoms of the disease.

Genetic counseling "increases the accuracy of risk perception; decreases intention for mutation testing among women who are unlikely carriers; and decreases cancer worry, anxiety, and depression," according to the guideline writers. Routine genetic counseling and testing are not recommended for average-risk women.

BRCA1 and BRCA2 mutations occur in 0.2%-0.3% of women in the general population. The risk is higher in certain population subgroups: A meta-analysis showed that the combined prevalence of the mutations was 2.1% in a general population of Ashkenazi Jewish women, the guideline notes.

"Women should have their family history assessed to help make sure that clinicians identify the small number of women with BRCA mutations," Dr. Douglas K. Owens, a member of the U.S. Preventive Services Task Force (USPSTF), said in an interview. He emphasized that "most women would not need or not benefit from BRCA testing; it’s really a small minority."

The task force said that the new guideline reaffirms its 2005 recommendation on BRCA testing, but noted that an update was in order because "the potential benefits and harms of medications for breast cancer risk reduction have been studied for longer follow-up periods, and more information is available about the potential psychological effects of genetic counseling and risk-reducing surgery."

Additionally, family history risk-stratification tools are now available and have been developed and validated for use in primary care settings to guide referrals for BRCA genetic counseling. These include the Ontario Family History Assessment Tool, the Manchester Scoring System, the six-question Referral Screening Tool, the Pedigree Assessment Tool, and a seven-question family history screening instrument known as the FHS-7. These tools, which are all estimated to be more than 85% sensitive, "elicit information about factors associated with increased likelihood of BRCA mutations," wrote the members of the task force, which was chaired by Dr. Virginia A. Moyer, vice president for maintenance of certification and quality at the American Board of Pediatrics.

"The USPSTF recognizes that each risk-assessment tool has limitations, and found insufficient evidence to recommend one tool over another," the task force members wrote.

The guideline does not recommend a specific course of action for women who test positive for BRCA gene mutations. Options for women to consider include "intensive surveillance for breast cancer primarily, consideration of medications to reduce the risk of breast cancer, and either prophylactic mastectomy or prophylactic oophorectomy. If someone is BRCA-positive, the role of the primary care clinician is to have an initial discussion of what the person would like to consider. These would be discussions that might include other kinds of clinicians as well," said Dr. Owens, director of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University.

Before issuing the new guideline, task force members reviewed evidence published in 2004 or later related to risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA mutations in asymptomatic women with a family history of breast or ovarian cancer but no personal history of cancer or known potentially harmful BRCA mutations in their family. They also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations.

In its evidence review, the task force concluded that limitations of studies included differences in designs and measures, dissimilar comparison groups, and small sizes. "Risk perception improved after receiving test results, and breast cancer worry and anxiety increased for women with positive results and decreased for others, although results were inconsistent. Studies were limited by high loss to follow-up and differences between comparison groups. Other relevant adverse effects of genetic testing were not studied, including false positive or negative results, genetic discrimination, and insurability."

The task force called for efforts to determine the appropriateness of risk assessment and testing for BRCA mutations in primary care, including research "on access to testing, effectiveness of screening approaches including risk stratification, use of system supports, and patient acceptance and education. Trials comparing types of providers and protocols could address questions about who should perform these services, how they should be done, and what skills are required. The consequences of identifying women as high risk, as well as genetic testing of individuals and their relatives, require more study."

The full recommendation is available here.

The review was funded by the Agency for Health Research and Quality. Task force member Dr. Kirsten Bibbins-Domingo disclosed that she has received grants from the American Heart Association, the Centers for Disease Control and Prevention, and the National Institutes of Health. Task force member Dr. Michael P. Pignone disclosed that he has received a grant from the American Cancer Society. The other task force members stated that they had no relevant financial disclosures.

dbrunk@frontlinemedcom.com

Asymptomatic women with a family history of breast, ovarian, tubal, or peritoneal cancers should be screened for potentially increased risk for BRCA mutations, according to a new guideline from the U.S. Preventive Services Task Force.

Those with positive screening results should undergo genetic counseling to determine whether they should be tested for mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, according to the guideline, which was published online Dec. 23 in Annals of Internal Medicine. The guideline applies only to at-risk women who have not been previously diagnosed with BRCA-related cancer and who have no signs or symptoms of the disease.

Genetic counseling "increases the accuracy of risk perception; decreases intention for mutation testing among women who are unlikely carriers; and decreases cancer worry, anxiety, and depression," according to the guideline writers. Routine genetic counseling and testing are not recommended for average-risk women.

BRCA1 and BRCA2 mutations occur in 0.2%-0.3% of women in the general population. The risk is higher in certain population subgroups: A meta-analysis showed that the combined prevalence of the mutations was 2.1% in a general population of Ashkenazi Jewish women, the guideline notes.

"Women should have their family history assessed to help make sure that clinicians identify the small number of women with BRCA mutations," Dr. Douglas K. Owens, a member of the U.S. Preventive Services Task Force (USPSTF), said in an interview. He emphasized that "most women would not need or not benefit from BRCA testing; it’s really a small minority."

The task force said that the new guideline reaffirms its 2005 recommendation on BRCA testing, but noted that an update was in order because "the potential benefits and harms of medications for breast cancer risk reduction have been studied for longer follow-up periods, and more information is available about the potential psychological effects of genetic counseling and risk-reducing surgery."

Additionally, family history risk-stratification tools are now available and have been developed and validated for use in primary care settings to guide referrals for BRCA genetic counseling. These include the Ontario Family History Assessment Tool, the Manchester Scoring System, the six-question Referral Screening Tool, the Pedigree Assessment Tool, and a seven-question family history screening instrument known as the FHS-7. These tools, which are all estimated to be more than 85% sensitive, "elicit information about factors associated with increased likelihood of BRCA mutations," wrote the members of the task force, which was chaired by Dr. Virginia A. Moyer, vice president for maintenance of certification and quality at the American Board of Pediatrics.

"The USPSTF recognizes that each risk-assessment tool has limitations, and found insufficient evidence to recommend one tool over another," the task force members wrote.

The guideline does not recommend a specific course of action for women who test positive for BRCA gene mutations. Options for women to consider include "intensive surveillance for breast cancer primarily, consideration of medications to reduce the risk of breast cancer, and either prophylactic mastectomy or prophylactic oophorectomy. If someone is BRCA-positive, the role of the primary care clinician is to have an initial discussion of what the person would like to consider. These would be discussions that might include other kinds of clinicians as well," said Dr. Owens, director of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University.

Before issuing the new guideline, task force members reviewed evidence published in 2004 or later related to risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA mutations in asymptomatic women with a family history of breast or ovarian cancer but no personal history of cancer or known potentially harmful BRCA mutations in their family. They also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations.

In its evidence review, the task force concluded that limitations of studies included differences in designs and measures, dissimilar comparison groups, and small sizes. "Risk perception improved after receiving test results, and breast cancer worry and anxiety increased for women with positive results and decreased for others, although results were inconsistent. Studies were limited by high loss to follow-up and differences between comparison groups. Other relevant adverse effects of genetic testing were not studied, including false positive or negative results, genetic discrimination, and insurability."

The task force called for efforts to determine the appropriateness of risk assessment and testing for BRCA mutations in primary care, including research "on access to testing, effectiveness of screening approaches including risk stratification, use of system supports, and patient acceptance and education. Trials comparing types of providers and protocols could address questions about who should perform these services, how they should be done, and what skills are required. The consequences of identifying women as high risk, as well as genetic testing of individuals and their relatives, require more study."

The full recommendation is available here.

The review was funded by the Agency for Health Research and Quality. Task force member Dr. Kirsten Bibbins-Domingo disclosed that she has received grants from the American Heart Association, the Centers for Disease Control and Prevention, and the National Institutes of Health. Task force member Dr. Michael P. Pignone disclosed that he has received a grant from the American Cancer Society. The other task force members stated that they had no relevant financial disclosures.

dbrunk@frontlinemedcom.com

Asymptomatic women with a family history of breast, ovarian, tubal, or peritoneal cancers should be screened for potentially increased risk for BRCA mutations, according to a new guideline from the U.S. Preventive Services Task Force.

Those with positive screening results should undergo genetic counseling to determine whether they should be tested for mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, according to the guideline, which was published online Dec. 23 in Annals of Internal Medicine. The guideline applies only to at-risk women who have not been previously diagnosed with BRCA-related cancer and who have no signs or symptoms of the disease.

Genetic counseling "increases the accuracy of risk perception; decreases intention for mutation testing among women who are unlikely carriers; and decreases cancer worry, anxiety, and depression," according to the guideline writers. Routine genetic counseling and testing are not recommended for average-risk women.

BRCA1 and BRCA2 mutations occur in 0.2%-0.3% of women in the general population. The risk is higher in certain population subgroups: A meta-analysis showed that the combined prevalence of the mutations was 2.1% in a general population of Ashkenazi Jewish women, the guideline notes.

"Women should have their family history assessed to help make sure that clinicians identify the small number of women with BRCA mutations," Dr. Douglas K. Owens, a member of the U.S. Preventive Services Task Force (USPSTF), said in an interview. He emphasized that "most women would not need or not benefit from BRCA testing; it’s really a small minority."

The task force said that the new guideline reaffirms its 2005 recommendation on BRCA testing, but noted that an update was in order because "the potential benefits and harms of medications for breast cancer risk reduction have been studied for longer follow-up periods, and more information is available about the potential psychological effects of genetic counseling and risk-reducing surgery."

Additionally, family history risk-stratification tools are now available and have been developed and validated for use in primary care settings to guide referrals for BRCA genetic counseling. These include the Ontario Family History Assessment Tool, the Manchester Scoring System, the six-question Referral Screening Tool, the Pedigree Assessment Tool, and a seven-question family history screening instrument known as the FHS-7. These tools, which are all estimated to be more than 85% sensitive, "elicit information about factors associated with increased likelihood of BRCA mutations," wrote the members of the task force, which was chaired by Dr. Virginia A. Moyer, vice president for maintenance of certification and quality at the American Board of Pediatrics.

"The USPSTF recognizes that each risk-assessment tool has limitations, and found insufficient evidence to recommend one tool over another," the task force members wrote.

The guideline does not recommend a specific course of action for women who test positive for BRCA gene mutations. Options for women to consider include "intensive surveillance for breast cancer primarily, consideration of medications to reduce the risk of breast cancer, and either prophylactic mastectomy or prophylactic oophorectomy. If someone is BRCA-positive, the role of the primary care clinician is to have an initial discussion of what the person would like to consider. These would be discussions that might include other kinds of clinicians as well," said Dr. Owens, director of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University.

Before issuing the new guideline, task force members reviewed evidence published in 2004 or later related to risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA mutations in asymptomatic women with a family history of breast or ovarian cancer but no personal history of cancer or known potentially harmful BRCA mutations in their family. They also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations.

In its evidence review, the task force concluded that limitations of studies included differences in designs and measures, dissimilar comparison groups, and small sizes. "Risk perception improved after receiving test results, and breast cancer worry and anxiety increased for women with positive results and decreased for others, although results were inconsistent. Studies were limited by high loss to follow-up and differences between comparison groups. Other relevant adverse effects of genetic testing were not studied, including false positive or negative results, genetic discrimination, and insurability."

The task force called for efforts to determine the appropriateness of risk assessment and testing for BRCA mutations in primary care, including research "on access to testing, effectiveness of screening approaches including risk stratification, use of system supports, and patient acceptance and education. Trials comparing types of providers and protocols could address questions about who should perform these services, how they should be done, and what skills are required. The consequences of identifying women as high risk, as well as genetic testing of individuals and their relatives, require more study."

The full recommendation is available here.

The review was funded by the Agency for Health Research and Quality. Task force member Dr. Kirsten Bibbins-Domingo disclosed that she has received grants from the American Heart Association, the Centers for Disease Control and Prevention, and the National Institutes of Health. Task force member Dr. Michael P. Pignone disclosed that he has received a grant from the American Cancer Society. The other task force members stated that they had no relevant financial disclosures.

dbrunk@frontlinemedcom.com

SAN ANTONIO – African-American women had half the risk of developing estrogen receptor–negative breast cancer if they exercised vigorously 3 hours per week, according to data from the Black Women’s Health Study.

The findings are based on nearly 20 years of follow-up on 44,704 women in the prospective, observational Black Women's Health Study. During this period, 1,377 subjects were diagnosed with invasive breast cancer, including 327 with ER-negative disease.

©monkeybusinessimages/thinkstockphotos.com

Black women who reported having engaged in vigorous exercise from high school onwards for a lifetime average of 3 hours or more per week had a 47% reduction in the risk of ER-negative breast cancer, compared with women exercising vigorously for less than 1 hour per week after adjusting for age, education, parity, and dietary pattern, Lucile Adams-Campbell, Ph.D., said at the San Antonio Breast Cancer Symposium.

Exercise proved unrelated to the risk of developing the generally more indolent ER-positive breast cancers in this population, said Dr. Adams-Campbell, professor of oncology at the Georgetown University Lombardi Comprehensive Cancer Center in Washington, D.C.

The inverse relationship between vigorous exercise and ER-negative breast cancer risk was statistically significant only among postmenopausal black women. In that population, the adjusted risk was reduced by 59% in participants with a lifetime average of at least 3 hours of exercise per week, compared with less than 1 hour.

The Centers for Disease Control and Prevention defines vigorous exercise as more than 6.0 metabolic equivalents (more than 7 kcal/min). Examples of activities through which this is readily accomplished include jogging, bicycling at more than 10 mph, or briskly walking uphill.

Dr. Adams-Campbell is a coleader of the ongoing Black Women’s Health Study, which aims to shed light on the elevated risks of hypertension, stroke, diabetes, lupus, and other diseases present in African-American women. The study is funded by the National Cancer Institute. Dr. Adams-Campbell reported having no relevant financial interests.

bjancin@frontlinemedcom.com

SAN ANTONIO – African-American women had half the risk of developing estrogen receptor–negative breast cancer if they exercised vigorously 3 hours per week, according to data from the Black Women’s Health Study.

The findings are based on nearly 20 years of follow-up on 44,704 women in the prospective, observational Black Women's Health Study. During this period, 1,377 subjects were diagnosed with invasive breast cancer, including 327 with ER-negative disease.

©monkeybusinessimages/thinkstockphotos.com

Black women who reported having engaged in vigorous exercise from high school onwards for a lifetime average of 3 hours or more per week had a 47% reduction in the risk of ER-negative breast cancer, compared with women exercising vigorously for less than 1 hour per week after adjusting for age, education, parity, and dietary pattern, Lucile Adams-Campbell, Ph.D., said at the San Antonio Breast Cancer Symposium.

Exercise proved unrelated to the risk of developing the generally more indolent ER-positive breast cancers in this population, said Dr. Adams-Campbell, professor of oncology at the Georgetown University Lombardi Comprehensive Cancer Center in Washington, D.C.

The inverse relationship between vigorous exercise and ER-negative breast cancer risk was statistically significant only among postmenopausal black women. In that population, the adjusted risk was reduced by 59% in participants with a lifetime average of at least 3 hours of exercise per week, compared with less than 1 hour.

The Centers for Disease Control and Prevention defines vigorous exercise as more than 6.0 metabolic equivalents (more than 7 kcal/min). Examples of activities through which this is readily accomplished include jogging, bicycling at more than 10 mph, or briskly walking uphill.

Dr. Adams-Campbell is a coleader of the ongoing Black Women’s Health Study, which aims to shed light on the elevated risks of hypertension, stroke, diabetes, lupus, and other diseases present in African-American women. The study is funded by the National Cancer Institute. Dr. Adams-Campbell reported having no relevant financial interests.

bjancin@frontlinemedcom.com

SAN ANTONIO – African-American women had half the risk of developing estrogen receptor–negative breast cancer if they exercised vigorously 3 hours per week, according to data from the Black Women’s Health Study.

The findings are based on nearly 20 years of follow-up on 44,704 women in the prospective, observational Black Women's Health Study. During this period, 1,377 subjects were diagnosed with invasive breast cancer, including 327 with ER-negative disease.

©monkeybusinessimages/thinkstockphotos.com

Black women who reported having engaged in vigorous exercise from high school onwards for a lifetime average of 3 hours or more per week had a 47% reduction in the risk of ER-negative breast cancer, compared with women exercising vigorously for less than 1 hour per week after adjusting for age, education, parity, and dietary pattern, Lucile Adams-Campbell, Ph.D., said at the San Antonio Breast Cancer Symposium.

Exercise proved unrelated to the risk of developing the generally more indolent ER-positive breast cancers in this population, said Dr. Adams-Campbell, professor of oncology at the Georgetown University Lombardi Comprehensive Cancer Center in Washington, D.C.

The inverse relationship between vigorous exercise and ER-negative breast cancer risk was statistically significant only among postmenopausal black women. In that population, the adjusted risk was reduced by 59% in participants with a lifetime average of at least 3 hours of exercise per week, compared with less than 1 hour.

The Centers for Disease Control and Prevention defines vigorous exercise as more than 6.0 metabolic equivalents (more than 7 kcal/min). Examples of activities through which this is readily accomplished include jogging, bicycling at more than 10 mph, or briskly walking uphill.

Dr. Adams-Campbell is a coleader of the ongoing Black Women’s Health Study, which aims to shed light on the elevated risks of hypertension, stroke, diabetes, lupus, and other diseases present in African-American women. The study is funded by the National Cancer Institute. Dr. Adams-Campbell reported having no relevant financial interests.

bjancin@frontlinemedcom.com

SAN ANTONIO – Tumor-infiltrating lymphocyte levels at breast cancer diagnosis predict response to therapies for both HER2-positive and triple-negative breast cancers, according to studies presented at the San Antonio Breast Cancer Symposium.

Tumor-infiltrating lymphocytes (TILs) appeared to be a useful biomarker of response to trastuzumab (Herceptin) as well as to chemotherapy. By extension, breast cancers appear to be immunogenic, contrary to traditional thinking. Trastuzumab and chemotherapy appear to act not only on the tumor, but to enhance antitumor immunity as well.

The findings could result in a paradigm shift in treatment approaches. Clinical outcomes could potentially be improved in women with HER2-positive or triple-negative breast cancers by targeting the immune system with immunomodulatory agents in addition to providing standard therapies, according to Dr. Sherene Loi, a medical oncologist and head of the translational breast cancer genomics laboratory at the Peter MacCallum Cancer Center in Melbourne.

Dr. Loi presented an analysis of breast cancer samples from 156 women with operable or locally advanced HER2-positive breast cancer who participated in the previously reported GeparQuattro trial. All of the women received neoadjuvant trastuzumab and cytotoxic chemotherapy. In a multivariate analysis, for every 10% increase in the level of stromal TILs there was a 16% increase in the pathologic complete response rate, meaning no residual invasive cancer in the breast or lymph nodes at surgery.

"These data reinforced for us that there is a relationship between the immune system and responses to trastuzumab and chemotherapy," she said.

In another study presented at the meeting, Dr. Sylvia Adams demonstrated the prognostic value of TILs in patients with triple-negative breast cancer. Tumors were analyzed from 481 participants in Eastern Cooperative Oncology Group 2197 and 1199, two previously reported phase III randomized, prospective trials of adjuvant chemotherapy in triple-negative breast cancer.

At least 10% lymphocytic infiltration in the tumor stroma was seen in 80% of tumors, meaning that 10% or more of all cells in the stroma were TILs. For each 10% increment in stromal TILs at the time of breast cancer diagnosis, there was an 18% reduction in the risk of distant recurrence and a "very impressive" 19% reduction in the risk of mortality at a median followup of 10.6 years, reported Dr. Adams of New York University.

She noted that this new analysis confirms an earlier study led by Dr. Loi, the prospective, randomized BIG 02-98 trial. In that study, TILs were associated with improved prognosis in patients with operable triple-negative breast cancer. The new validation study, Dr. Adams noted, raises to Level I the evidence that supports measuring stromal TILs as a biomarker in triple-negative breast cancer.

"The data provide strong evidence for the incorporation of this feature into the AJCC (American Joint Committee on Cancer) staging for triple-negative breast cancer and for utilization of stromal TILs as a stratifier in clinical trials," Dr. Adams said. "And most important, I would like to say – because some may ask ‘Is this just another prognostic factor for breast cancer?’ – is that these data really help provide additional evidence that some breast cancers can be immunogenic and that the endogenous immune response to cancer is predictive of survival in triple-negative breast cancer. So this actually opens up the area for introducing immunotherapies in triple-negative breast cancer. There is a hope that by targeting and harnessing the immune system we can improve cure rates."

Dr. Loi provided a glimpse into the possible way forward. In an effort to learn how trastuzumab affects antitumor immunity, she and her colleagues performed gene expression analyses on HER2-positive breast tumor specimens from 202 participants in the phase III randomized FinHER clinical trial of adjuvant trastuzumab or no trastuzumab along with postoperative chemotherapy. The greatest clinical response to trastuzumab was seen in patients whose tumors highly expressed the immunosuppressive gene known as programmed cell death 1 (PD-1).

This led to studies conducted in a mouse model of HER2-positive breast cancer. Dr. Loi and her colleagues showed that combining trastuzumab with a T-cell checkpoint inhibitor – an anti-PD-1 agent resulted in greater reductions in tumor size than with trastuzumab alone.

More than half a dozen T-cell checkpoint inhibitors are in the developmental pipeline for treatment of a range of malignancies, including the anti-PD-1 agents nivolumab, lambrolizumab, and pidilizumab. Clinical trials testing the combination of trastuzumab and a PD-1 inhibitor in HER2-positive breast cancer patients are being planned.

Dr. Loi’s work was funded by the European Union RESPONSIFY project, the Breast Cancer Research Foundation, and the Fonds J.C. Heuson. She and Dr. Adams reported having no relevant financial conflicts of interest.

bjancin@frontlinemedcom.com

SAN ANTONIO – Tumor-infiltrating lymphocyte levels at breast cancer diagnosis predict response to therapies for both HER2-positive and triple-negative breast cancers, according to studies presented at the San Antonio Breast Cancer Symposium.

Tumor-infiltrating lymphocytes (TILs) appeared to be a useful biomarker of response to trastuzumab (Herceptin) as well as to chemotherapy. By extension, breast cancers appear to be immunogenic, contrary to traditional thinking. Trastuzumab and chemotherapy appear to act not only on the tumor, but to enhance antitumor immunity as well.

The findings could result in a paradigm shift in treatment approaches. Clinical outcomes could potentially be improved in women with HER2-positive or triple-negative breast cancers by targeting the immune system with immunomodulatory agents in addition to providing standard therapies, according to Dr. Sherene Loi, a medical oncologist and head of the translational breast cancer genomics laboratory at the Peter MacCallum Cancer Center in Melbourne.

Dr. Loi presented an analysis of breast cancer samples from 156 women with operable or locally advanced HER2-positive breast cancer who participated in the previously reported GeparQuattro trial. All of the women received neoadjuvant trastuzumab and cytotoxic chemotherapy. In a multivariate analysis, for every 10% increase in the level of stromal TILs there was a 16% increase in the pathologic complete response rate, meaning no residual invasive cancer in the breast or lymph nodes at surgery.

"These data reinforced for us that there is a relationship between the immune system and responses to trastuzumab and chemotherapy," she said.

In another study presented at the meeting, Dr. Sylvia Adams demonstrated the prognostic value of TILs in patients with triple-negative breast cancer. Tumors were analyzed from 481 participants in Eastern Cooperative Oncology Group 2197 and 1199, two previously reported phase III randomized, prospective trials of adjuvant chemotherapy in triple-negative breast cancer.

At least 10% lymphocytic infiltration in the tumor stroma was seen in 80% of tumors, meaning that 10% or more of all cells in the stroma were TILs. For each 10% increment in stromal TILs at the time of breast cancer diagnosis, there was an 18% reduction in the risk of distant recurrence and a "very impressive" 19% reduction in the risk of mortality at a median followup of 10.6 years, reported Dr. Adams of New York University.

She noted that this new analysis confirms an earlier study led by Dr. Loi, the prospective, randomized BIG 02-98 trial. In that study, TILs were associated with improved prognosis in patients with operable triple-negative breast cancer. The new validation study, Dr. Adams noted, raises to Level I the evidence that supports measuring stromal TILs as a biomarker in triple-negative breast cancer.

"The data provide strong evidence for the incorporation of this feature into the AJCC (American Joint Committee on Cancer) staging for triple-negative breast cancer and for utilization of stromal TILs as a stratifier in clinical trials," Dr. Adams said. "And most important, I would like to say – because some may ask ‘Is this just another prognostic factor for breast cancer?’ – is that these data really help provide additional evidence that some breast cancers can be immunogenic and that the endogenous immune response to cancer is predictive of survival in triple-negative breast cancer. So this actually opens up the area for introducing immunotherapies in triple-negative breast cancer. There is a hope that by targeting and harnessing the immune system we can improve cure rates."

Dr. Loi provided a glimpse into the possible way forward. In an effort to learn how trastuzumab affects antitumor immunity, she and her colleagues performed gene expression analyses on HER2-positive breast tumor specimens from 202 participants in the phase III randomized FinHER clinical trial of adjuvant trastuzumab or no trastuzumab along with postoperative chemotherapy. The greatest clinical response to trastuzumab was seen in patients whose tumors highly expressed the immunosuppressive gene known as programmed cell death 1 (PD-1).

This led to studies conducted in a mouse model of HER2-positive breast cancer. Dr. Loi and her colleagues showed that combining trastuzumab with a T-cell checkpoint inhibitor – an anti-PD-1 agent resulted in greater reductions in tumor size than with trastuzumab alone.

More than half a dozen T-cell checkpoint inhibitors are in the developmental pipeline for treatment of a range of malignancies, including the anti-PD-1 agents nivolumab, lambrolizumab, and pidilizumab. Clinical trials testing the combination of trastuzumab and a PD-1 inhibitor in HER2-positive breast cancer patients are being planned.

Dr. Loi’s work was funded by the European Union RESPONSIFY project, the Breast Cancer Research Foundation, and the Fonds J.C. Heuson. She and Dr. Adams reported having no relevant financial conflicts of interest.

bjancin@frontlinemedcom.com

SAN ANTONIO – Tumor-infiltrating lymphocyte levels at breast cancer diagnosis predict response to therapies for both HER2-positive and triple-negative breast cancers, according to studies presented at the San Antonio Breast Cancer Symposium.

Tumor-infiltrating lymphocytes (TILs) appeared to be a useful biomarker of response to trastuzumab (Herceptin) as well as to chemotherapy. By extension, breast cancers appear to be immunogenic, contrary to traditional thinking. Trastuzumab and chemotherapy appear to act not only on the tumor, but to enhance antitumor immunity as well.

The findings could result in a paradigm shift in treatment approaches. Clinical outcomes could potentially be improved in women with HER2-positive or triple-negative breast cancers by targeting the immune system with immunomodulatory agents in addition to providing standard therapies, according to Dr. Sherene Loi, a medical oncologist and head of the translational breast cancer genomics laboratory at the Peter MacCallum Cancer Center in Melbourne.

Dr. Loi presented an analysis of breast cancer samples from 156 women with operable or locally advanced HER2-positive breast cancer who participated in the previously reported GeparQuattro trial. All of the women received neoadjuvant trastuzumab and cytotoxic chemotherapy. In a multivariate analysis, for every 10% increase in the level of stromal TILs there was a 16% increase in the pathologic complete response rate, meaning no residual invasive cancer in the breast or lymph nodes at surgery.

"These data reinforced for us that there is a relationship between the immune system and responses to trastuzumab and chemotherapy," she said.

In another study presented at the meeting, Dr. Sylvia Adams demonstrated the prognostic value of TILs in patients with triple-negative breast cancer. Tumors were analyzed from 481 participants in Eastern Cooperative Oncology Group 2197 and 1199, two previously reported phase III randomized, prospective trials of adjuvant chemotherapy in triple-negative breast cancer.

At least 10% lymphocytic infiltration in the tumor stroma was seen in 80% of tumors, meaning that 10% or more of all cells in the stroma were TILs. For each 10% increment in stromal TILs at the time of breast cancer diagnosis, there was an 18% reduction in the risk of distant recurrence and a "very impressive" 19% reduction in the risk of mortality at a median followup of 10.6 years, reported Dr. Adams of New York University.

She noted that this new analysis confirms an earlier study led by Dr. Loi, the prospective, randomized BIG 02-98 trial. In that study, TILs were associated with improved prognosis in patients with operable triple-negative breast cancer. The new validation study, Dr. Adams noted, raises to Level I the evidence that supports measuring stromal TILs as a biomarker in triple-negative breast cancer.

"The data provide strong evidence for the incorporation of this feature into the AJCC (American Joint Committee on Cancer) staging for triple-negative breast cancer and for utilization of stromal TILs as a stratifier in clinical trials," Dr. Adams said. "And most important, I would like to say – because some may ask ‘Is this just another prognostic factor for breast cancer?’ – is that these data really help provide additional evidence that some breast cancers can be immunogenic and that the endogenous immune response to cancer is predictive of survival in triple-negative breast cancer. So this actually opens up the area for introducing immunotherapies in triple-negative breast cancer. There is a hope that by targeting and harnessing the immune system we can improve cure rates."

Dr. Loi provided a glimpse into the possible way forward. In an effort to learn how trastuzumab affects antitumor immunity, she and her colleagues performed gene expression analyses on HER2-positive breast tumor specimens from 202 participants in the phase III randomized FinHER clinical trial of adjuvant trastuzumab or no trastuzumab along with postoperative chemotherapy. The greatest clinical response to trastuzumab was seen in patients whose tumors highly expressed the immunosuppressive gene known as programmed cell death 1 (PD-1).

This led to studies conducted in a mouse model of HER2-positive breast cancer. Dr. Loi and her colleagues showed that combining trastuzumab with a T-cell checkpoint inhibitor – an anti-PD-1 agent resulted in greater reductions in tumor size than with trastuzumab alone.

More than half a dozen T-cell checkpoint inhibitors are in the developmental pipeline for treatment of a range of malignancies, including the anti-PD-1 agents nivolumab, lambrolizumab, and pidilizumab. Clinical trials testing the combination of trastuzumab and a PD-1 inhibitor in HER2-positive breast cancer patients are being planned.

Dr. Loi’s work was funded by the European Union RESPONSIFY project, the Breast Cancer Research Foundation, and the Fonds J.C. Heuson. She and Dr. Adams reported having no relevant financial conflicts of interest.

bjancin@frontlinemedcom.com