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Breast cancer margins, radiotherapy, axillary dissection evolve
SAN FRANCISCO – Recent research and guidelines have changed how surgeons should be thinking about some aspects of treating breast cancer, a panel of experts said in a press briefing at the annual clinical congress of the American College of Surgeons.
New guidelines on surgical margins, data supporting radiation rather than complete lymphadenectomy for patients with positive sentinel nodes, and other studies supporting targeted radiation therapy instead of whole-breast irradiation after lumpectomy should be on a surgeons’s radar, the speakers said.
The first U.S. guidelines on surgical margins for lumpectomy in women with breast cancer who are planning to undergo whole-breast radiation therapy adopted a standard of “no ink on tumor,” meaning no cancer at the edge of the tissue that was removed, Dr. Richard J. Gray said. The 2014 joint guidelines from the Society of Surgical Oncology and the American Society of Radiation Oncology based the recommendations on a meta-analysis of studies that found no advantage to wider excision margins for preventing in-breast recurrence (Ann. Surg. Oncol. 2014;21:717-730).
Previously, many surgeons sought to take 1, 2, or 3 mm of normal tissue around the cancer removed to reduce the risk of recurrence, he said.
“This guideline will become the standard throughout the United States. The evidence on which this is based is reasonable, but it will be important for individual institutions and national databases to track the rates of local recurrence over time as these guidelines are implemented,” said Dr. Gray of the Mayo Clinic, Scottsdale, Ariz. He confessed to being “a recovering addict” to margins of 2 mm or greater.
The guidelines apply only to patients with invasive cancer undergoing breast-conserving treatment, he noted. There are no guidelines yet specifically for surgical margins in women undergoing mastectomy for breast cancer, nor for women with ductal carcinoma in situ (DCIS).
While there is no evidence that a margin width wider than “no ink on tumor” is better for women undergoing mastectomy, Dr. Gray cautioned against extrapolating the guidelines to women having mastectomies “because they will generally not undergo adjuvant radiation therapy,” he said.
For women with DCIS, the available evidence suggests that a minimum 2-mm margin of excision is reasonable for those undergoing lumpectomy or at least negative margins (no ink on tumor) for those undergoing mastectomy, Dr. Gray said. Wider margins may help select patients with DCIS who undergo lumpectomy to avoid adjuvant radiation therapy, he added.
A separate recent study should change the way surgeons approach decisions about axillary surgery in patients with breast cancer, Dr. Roshni Rao said. She reported on a study that randomized women who had cancer in sentinel lymph nodes after mastectomy to further treatment by removing the rest of the lymph nodes under the arm, as is common practice, or to radiation of the lymph nodes area.
Rates of cancer recurrence did not differ between groups but the radiation approach significantly reduced the risk of lymphedema and other morbidity, said Dr. Rao of the University of Texas Southwestern Medical Center, Dallas.
“Going forward, we’re going to be performing less and less axillary lymph node dissections,” she said.
Also on the topic of radiation therapy, two recent studies of targeted breast irradiation rather than whole-breast radiotherapy suggest that the targeted approach may be beneficial, Dr. Courtney A. Vito said. Whole-breast radiation after lumpectomy reduces the risk of local recurrence by 50%, previous studies have shown, but it comes with potential side effects including burns, lymphedema, and damage to underlying structures like the heart and lungs. Patients who don’t live near specialized radiation centers may not be able to access the daily month-long treatments.
A randomized Italian trial of 1,305 patients found similar rates of overall survival or breast cancer–specific survival in patients treated with whole-breast radiation therapy or with intraoperative radiation therapy, in which a single, more intense dose of radiation is directed just at the site of lumpectomy during surgery. Survival rates were similar between groups but the rate of local recurrence after 5 years was 10 times higher in the intraoperative radiation group (4.4%), compared with the whole-breast radiation group (0.4%) (Lancet Oncol. 2013;14:1269-77).
Subset analyses showed, however, that most of the recurrences were in women who would not be considered ideal candidates for intraoperative radiotherapy in the United States because they had tumors larger than 2 cm, four or more positive lymph nodes, estrogen receptor–negative tumors, or other aggressive tumor biology, said Dr. Vito of the City of Hope National Medical Center, Duarte, Calif. Recurrence rates were more favorable in patients with lower-risk tumors.
“When you take out the high-risk group, the data actually look a lot better,” she said.
A separate randomized British trial of intraoperative radiation therapy produced similar overall results in 1,721 patients, but two-thirds of patients would be considered unsuitable or cautionary in the United States, Dr. Vito said (Lancet 2014;383:603-613).
Overall survival and breast cancer survival were similar in the intraoperative and whole-breast radiation groups except for worse outcomes in patients who had intraoperative radiation done as a second surgery after the operation to perform lumpectomy.
The rate of deaths from causes other than breast cancer was higher in the whole-breast radiation group, in many cases due to cardiac events, Dr. Vito noted. Whole-breast radiation on the left side of the chest has been shown to accelerate atherosclerosis of the vessels in the heart, and it may be that avoiding this through intraoperative targeted radiotherapy may provide a cardiovascular benefit, though this is yet to be proven, she added.
A separate presentation at the meeting explored the increasing rate of women with cancer in one breast who choose prophylactic mastectomy of the healthy contralateral breast. The rate of prophylactic contralateral mastectomy increased 150% between 1998 and 2003 in the United States, from 1.8% to 4.5%, Dr. Swati Kulkarni said.
She and her associates surveyed a diverse cohort of 150 women before surgery for cancer in one breast and again 6 months after surgery. Only 14% said that medical staff had provided information about removing the healthy breast along with the cancerous breast; 63% said they did not get that information, and 23% were unsure, reported Dr. Kulkarni of the University of Chicago.
Thirty-nine percent of patients had thought about their surgical choices before they were diagnosed with breast cancer, and 58% of the cohort wanted or considered contralateral prophylactic mastectomy.
Patients with a family history of breast cancer who had undergone genetic testing were significantly more likely to want or consider prophylactic contralateral mastectomy. Factors that were not significantly associated with prophylactic contralateral mastectomy were family history by itself, age, race, insurance status, cancer stage, use of breast MRI, or having one or more biopsies.
The findings suggest that education about prophylactic mastectomy is needed “inside and outside of the doctor’s office,” Dr. Kulkarni said.
The speakers reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Recent research and guidelines have changed how surgeons should be thinking about some aspects of treating breast cancer, a panel of experts said in a press briefing at the annual clinical congress of the American College of Surgeons.
New guidelines on surgical margins, data supporting radiation rather than complete lymphadenectomy for patients with positive sentinel nodes, and other studies supporting targeted radiation therapy instead of whole-breast irradiation after lumpectomy should be on a surgeons’s radar, the speakers said.
The first U.S. guidelines on surgical margins for lumpectomy in women with breast cancer who are planning to undergo whole-breast radiation therapy adopted a standard of “no ink on tumor,” meaning no cancer at the edge of the tissue that was removed, Dr. Richard J. Gray said. The 2014 joint guidelines from the Society of Surgical Oncology and the American Society of Radiation Oncology based the recommendations on a meta-analysis of studies that found no advantage to wider excision margins for preventing in-breast recurrence (Ann. Surg. Oncol. 2014;21:717-730).
Previously, many surgeons sought to take 1, 2, or 3 mm of normal tissue around the cancer removed to reduce the risk of recurrence, he said.
“This guideline will become the standard throughout the United States. The evidence on which this is based is reasonable, but it will be important for individual institutions and national databases to track the rates of local recurrence over time as these guidelines are implemented,” said Dr. Gray of the Mayo Clinic, Scottsdale, Ariz. He confessed to being “a recovering addict” to margins of 2 mm or greater.
The guidelines apply only to patients with invasive cancer undergoing breast-conserving treatment, he noted. There are no guidelines yet specifically for surgical margins in women undergoing mastectomy for breast cancer, nor for women with ductal carcinoma in situ (DCIS).
While there is no evidence that a margin width wider than “no ink on tumor” is better for women undergoing mastectomy, Dr. Gray cautioned against extrapolating the guidelines to women having mastectomies “because they will generally not undergo adjuvant radiation therapy,” he said.
For women with DCIS, the available evidence suggests that a minimum 2-mm margin of excision is reasonable for those undergoing lumpectomy or at least negative margins (no ink on tumor) for those undergoing mastectomy, Dr. Gray said. Wider margins may help select patients with DCIS who undergo lumpectomy to avoid adjuvant radiation therapy, he added.
A separate recent study should change the way surgeons approach decisions about axillary surgery in patients with breast cancer, Dr. Roshni Rao said. She reported on a study that randomized women who had cancer in sentinel lymph nodes after mastectomy to further treatment by removing the rest of the lymph nodes under the arm, as is common practice, or to radiation of the lymph nodes area.
Rates of cancer recurrence did not differ between groups but the radiation approach significantly reduced the risk of lymphedema and other morbidity, said Dr. Rao of the University of Texas Southwestern Medical Center, Dallas.
“Going forward, we’re going to be performing less and less axillary lymph node dissections,” she said.
Also on the topic of radiation therapy, two recent studies of targeted breast irradiation rather than whole-breast radiotherapy suggest that the targeted approach may be beneficial, Dr. Courtney A. Vito said. Whole-breast radiation after lumpectomy reduces the risk of local recurrence by 50%, previous studies have shown, but it comes with potential side effects including burns, lymphedema, and damage to underlying structures like the heart and lungs. Patients who don’t live near specialized radiation centers may not be able to access the daily month-long treatments.
A randomized Italian trial of 1,305 patients found similar rates of overall survival or breast cancer–specific survival in patients treated with whole-breast radiation therapy or with intraoperative radiation therapy, in which a single, more intense dose of radiation is directed just at the site of lumpectomy during surgery. Survival rates were similar between groups but the rate of local recurrence after 5 years was 10 times higher in the intraoperative radiation group (4.4%), compared with the whole-breast radiation group (0.4%) (Lancet Oncol. 2013;14:1269-77).
Subset analyses showed, however, that most of the recurrences were in women who would not be considered ideal candidates for intraoperative radiotherapy in the United States because they had tumors larger than 2 cm, four or more positive lymph nodes, estrogen receptor–negative tumors, or other aggressive tumor biology, said Dr. Vito of the City of Hope National Medical Center, Duarte, Calif. Recurrence rates were more favorable in patients with lower-risk tumors.
“When you take out the high-risk group, the data actually look a lot better,” she said.
A separate randomized British trial of intraoperative radiation therapy produced similar overall results in 1,721 patients, but two-thirds of patients would be considered unsuitable or cautionary in the United States, Dr. Vito said (Lancet 2014;383:603-613).
Overall survival and breast cancer survival were similar in the intraoperative and whole-breast radiation groups except for worse outcomes in patients who had intraoperative radiation done as a second surgery after the operation to perform lumpectomy.
The rate of deaths from causes other than breast cancer was higher in the whole-breast radiation group, in many cases due to cardiac events, Dr. Vito noted. Whole-breast radiation on the left side of the chest has been shown to accelerate atherosclerosis of the vessels in the heart, and it may be that avoiding this through intraoperative targeted radiotherapy may provide a cardiovascular benefit, though this is yet to be proven, she added.
A separate presentation at the meeting explored the increasing rate of women with cancer in one breast who choose prophylactic mastectomy of the healthy contralateral breast. The rate of prophylactic contralateral mastectomy increased 150% between 1998 and 2003 in the United States, from 1.8% to 4.5%, Dr. Swati Kulkarni said.
She and her associates surveyed a diverse cohort of 150 women before surgery for cancer in one breast and again 6 months after surgery. Only 14% said that medical staff had provided information about removing the healthy breast along with the cancerous breast; 63% said they did not get that information, and 23% were unsure, reported Dr. Kulkarni of the University of Chicago.
Thirty-nine percent of patients had thought about their surgical choices before they were diagnosed with breast cancer, and 58% of the cohort wanted or considered contralateral prophylactic mastectomy.
Patients with a family history of breast cancer who had undergone genetic testing were significantly more likely to want or consider prophylactic contralateral mastectomy. Factors that were not significantly associated with prophylactic contralateral mastectomy were family history by itself, age, race, insurance status, cancer stage, use of breast MRI, or having one or more biopsies.
The findings suggest that education about prophylactic mastectomy is needed “inside and outside of the doctor’s office,” Dr. Kulkarni said.
The speakers reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Recent research and guidelines have changed how surgeons should be thinking about some aspects of treating breast cancer, a panel of experts said in a press briefing at the annual clinical congress of the American College of Surgeons.
New guidelines on surgical margins, data supporting radiation rather than complete lymphadenectomy for patients with positive sentinel nodes, and other studies supporting targeted radiation therapy instead of whole-breast irradiation after lumpectomy should be on a surgeons’s radar, the speakers said.
The first U.S. guidelines on surgical margins for lumpectomy in women with breast cancer who are planning to undergo whole-breast radiation therapy adopted a standard of “no ink on tumor,” meaning no cancer at the edge of the tissue that was removed, Dr. Richard J. Gray said. The 2014 joint guidelines from the Society of Surgical Oncology and the American Society of Radiation Oncology based the recommendations on a meta-analysis of studies that found no advantage to wider excision margins for preventing in-breast recurrence (Ann. Surg. Oncol. 2014;21:717-730).
Previously, many surgeons sought to take 1, 2, or 3 mm of normal tissue around the cancer removed to reduce the risk of recurrence, he said.
“This guideline will become the standard throughout the United States. The evidence on which this is based is reasonable, but it will be important for individual institutions and national databases to track the rates of local recurrence over time as these guidelines are implemented,” said Dr. Gray of the Mayo Clinic, Scottsdale, Ariz. He confessed to being “a recovering addict” to margins of 2 mm or greater.
The guidelines apply only to patients with invasive cancer undergoing breast-conserving treatment, he noted. There are no guidelines yet specifically for surgical margins in women undergoing mastectomy for breast cancer, nor for women with ductal carcinoma in situ (DCIS).
While there is no evidence that a margin width wider than “no ink on tumor” is better for women undergoing mastectomy, Dr. Gray cautioned against extrapolating the guidelines to women having mastectomies “because they will generally not undergo adjuvant radiation therapy,” he said.
For women with DCIS, the available evidence suggests that a minimum 2-mm margin of excision is reasonable for those undergoing lumpectomy or at least negative margins (no ink on tumor) for those undergoing mastectomy, Dr. Gray said. Wider margins may help select patients with DCIS who undergo lumpectomy to avoid adjuvant radiation therapy, he added.
A separate recent study should change the way surgeons approach decisions about axillary surgery in patients with breast cancer, Dr. Roshni Rao said. She reported on a study that randomized women who had cancer in sentinel lymph nodes after mastectomy to further treatment by removing the rest of the lymph nodes under the arm, as is common practice, or to radiation of the lymph nodes area.
Rates of cancer recurrence did not differ between groups but the radiation approach significantly reduced the risk of lymphedema and other morbidity, said Dr. Rao of the University of Texas Southwestern Medical Center, Dallas.
“Going forward, we’re going to be performing less and less axillary lymph node dissections,” she said.
Also on the topic of radiation therapy, two recent studies of targeted breast irradiation rather than whole-breast radiotherapy suggest that the targeted approach may be beneficial, Dr. Courtney A. Vito said. Whole-breast radiation after lumpectomy reduces the risk of local recurrence by 50%, previous studies have shown, but it comes with potential side effects including burns, lymphedema, and damage to underlying structures like the heart and lungs. Patients who don’t live near specialized radiation centers may not be able to access the daily month-long treatments.
A randomized Italian trial of 1,305 patients found similar rates of overall survival or breast cancer–specific survival in patients treated with whole-breast radiation therapy or with intraoperative radiation therapy, in which a single, more intense dose of radiation is directed just at the site of lumpectomy during surgery. Survival rates were similar between groups but the rate of local recurrence after 5 years was 10 times higher in the intraoperative radiation group (4.4%), compared with the whole-breast radiation group (0.4%) (Lancet Oncol. 2013;14:1269-77).
Subset analyses showed, however, that most of the recurrences were in women who would not be considered ideal candidates for intraoperative radiotherapy in the United States because they had tumors larger than 2 cm, four or more positive lymph nodes, estrogen receptor–negative tumors, or other aggressive tumor biology, said Dr. Vito of the City of Hope National Medical Center, Duarte, Calif. Recurrence rates were more favorable in patients with lower-risk tumors.
“When you take out the high-risk group, the data actually look a lot better,” she said.
A separate randomized British trial of intraoperative radiation therapy produced similar overall results in 1,721 patients, but two-thirds of patients would be considered unsuitable or cautionary in the United States, Dr. Vito said (Lancet 2014;383:603-613).
Overall survival and breast cancer survival were similar in the intraoperative and whole-breast radiation groups except for worse outcomes in patients who had intraoperative radiation done as a second surgery after the operation to perform lumpectomy.
The rate of deaths from causes other than breast cancer was higher in the whole-breast radiation group, in many cases due to cardiac events, Dr. Vito noted. Whole-breast radiation on the left side of the chest has been shown to accelerate atherosclerosis of the vessels in the heart, and it may be that avoiding this through intraoperative targeted radiotherapy may provide a cardiovascular benefit, though this is yet to be proven, she added.
A separate presentation at the meeting explored the increasing rate of women with cancer in one breast who choose prophylactic mastectomy of the healthy contralateral breast. The rate of prophylactic contralateral mastectomy increased 150% between 1998 and 2003 in the United States, from 1.8% to 4.5%, Dr. Swati Kulkarni said.
She and her associates surveyed a diverse cohort of 150 women before surgery for cancer in one breast and again 6 months after surgery. Only 14% said that medical staff had provided information about removing the healthy breast along with the cancerous breast; 63% said they did not get that information, and 23% were unsure, reported Dr. Kulkarni of the University of Chicago.
Thirty-nine percent of patients had thought about their surgical choices before they were diagnosed with breast cancer, and 58% of the cohort wanted or considered contralateral prophylactic mastectomy.
Patients with a family history of breast cancer who had undergone genetic testing were significantly more likely to want or consider prophylactic contralateral mastectomy. Factors that were not significantly associated with prophylactic contralateral mastectomy were family history by itself, age, race, insurance status, cancer stage, use of breast MRI, or having one or more biopsies.
The findings suggest that education about prophylactic mastectomy is needed “inside and outside of the doctor’s office,” Dr. Kulkarni said.
The speakers reported having no financial disclosures.
On Twitter @sherryboschert
AT THE ACS CLINICAL CONGRESS
‘Chemo brain’ may have targetable causes
BOSTON – The risk for cognitive decline following cancer treatment varies by both cancer and therapy types, and can range from subtle changes to severe deficits, according to a researcher.
Patients who are older, have lower cognitive reserves, or have comorbidities such as cardiovascular disease or diabetes are at risk for cognitive problems following cancer treatment, said Tim A. Ahles, Ph.D., director of the Neurocognitive Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York.
“I think it’s important that we identify these modifiable risk factors for intervention, and some of the nonmodifiable risk factors that inform decision making,” he said at the Palliative Care in Oncology Symposium.
“When we talk about cognitive function, we’re really talking about how does cancer and cancer treatment impact on memory, concentration, executive function, or ability to multitask, the speed at which we process information,” he said.
Oncologists have known for decades that brain tumors and their treatment have a negative effect on cognitive function, particularly among children under 5 years of age, whose developing brains are sensitive to treatments such as chemotherapy, surgery, radiation, and high-dose steroids.
There is also a dose-response effect, with high-dose chemotherapy such as ablative regimens used for bone-marrow transplantation being associated with higher probability of cognitive problems.
Dr. Ahles noted that about two-thirds of adult survivors of childhood cancers develop chronic illnesses within 30 years of diagnosis, including cardiac and pulmonary disease, and diabetes and endocrine dysfunction.
“It turns out they’re also at higher risk for cognitive issues,” including white matter abnormalities and microvascular stroke, he said.
The population of survivors of brain tumors and childhood cancers is dwarfed, however, by the large and growing population of breast, colorectal, lung, and prostate cancer patients who are diagnosed every year and exposed to adjuvant therapies, he added.
Aging and cognitive reserve
Evidence from breast cancer studies has shown that about 20%-25% of patients have lower than expected cognitive functioning – based on age, education, occupation, and other factors – before they embark on adjuvant therapy.
“That’s actually a risk factor for posttreatment cognitive decline, so there’s something that’s already going on that’s disrupting the cognitive information-processing system before we even start adjuvant treatment that may be critically important in terms of their outcomes as survivors,” Dr. Ahles said.
A significant subset of women in longitudinal studies of breast cancer survivors – about 15%-30% – experience long-term posttreatment cognitive problems, making it imperative for researchers and clinicians to identify risk factors for persistent cognitive decline, he said.
There is evidence to suggest that cancer treatments may interplay with biologic factors at the cellular level to increase the risk for cognitive loss. For example, aging is associated with reduction in brain volume, decrease in white matter integrity, and decreases in vascularization and neurotransmitter activity.
The effects of age on the brain are attenuated, however, among patients with higher cognitive reserves, defined as a combination of innate and developed cognitive capacity. Cognitive reserve is influenced by a number of factors, including genetics, education, occupational attainment, and lifestyle.
High cognitive reserve has been associated with later onset of Alzheimer’s disease symptoms and smaller changes in cognitive function with normal aging or following a brain injury, Dr. Ahles noted.
In a longitudinal study of cognitive changes associated with adjuvant therapy for breast cancer, Dr. Ahles and colleagues found that both age and pretreatment cognitive reserve were related to posttreatment decline in processing speed in women exposed to chemotherapy, compared with those who did not have chemotherapy or with healthy controls. In addition, chemotherapy had a short-term impact on verbal ability. The authors found evidence to suggest the patterns they saw may be related to the combination of chemotherapy and tamoxifen.
Part of the difficulty of studying cognitive decline among older patients is the higher prevalence of changes associated with aging. Dr. Ahles pointed to a French longitudinal study of women over 65 being treated for breast cancer, in which investigators found that 41% of the study population had cognitive impairment before starting on adjuvant therapy.
Older adults may be more frail, with diminished biological reserves and lower resistance to stressors caused by “cumulative declines across a variety of physiological systems making you more vulnerable to adverse events,” Dr. Ahles said.
Aging and genetics
Genes associated with cognitive aging are also risk factors for posttreatment cognitive decline, notably the genetic variants of APOE, including the epsilon 4 (APOE-e4) allele linked to increased risk for early-onset Alzheimer’s disease.
Dr. Ahles and colleagues had previously shown that APOE-e4 may be a biomarker for increased risk for chemotherapy-induced cognitive decline. The adverse effects of APOE-e4 appear to be mitigated somewhat by smoking, because it may correct for a deficit in nicotinic receptor density and dopamine levels in carriers.
Another genetic factor linked to postchemotherapy cognitive decline is the Val158Met polymorphism of the gene encoding for Catechol-O-methyltransferase (COMT), an enzyme that degrades neurotransmitters such as dopamine. Patients with this polymorphism have rapid dopamine metabolism, resulting in reduced dopamine activity.
These findings point to potential molecular mechanisms for cognitive changes associated with chemotherapy, and suggest that therapies targeted at neurotransmitter systems may ameliorate the effect, Dr. Ahles said.
He noted that animal studies have shown that fluoxetine (Prozac) prevents deficits in behavior and hippocampal function associated with 5-fluourauracil (5-FU), and that nicotine patches have been shown to improve cognitive functioning in patients with mild cognitive impairment.
The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.
BOSTON – The risk for cognitive decline following cancer treatment varies by both cancer and therapy types, and can range from subtle changes to severe deficits, according to a researcher.
Patients who are older, have lower cognitive reserves, or have comorbidities such as cardiovascular disease or diabetes are at risk for cognitive problems following cancer treatment, said Tim A. Ahles, Ph.D., director of the Neurocognitive Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York.
“I think it’s important that we identify these modifiable risk factors for intervention, and some of the nonmodifiable risk factors that inform decision making,” he said at the Palliative Care in Oncology Symposium.
“When we talk about cognitive function, we’re really talking about how does cancer and cancer treatment impact on memory, concentration, executive function, or ability to multitask, the speed at which we process information,” he said.
Oncologists have known for decades that brain tumors and their treatment have a negative effect on cognitive function, particularly among children under 5 years of age, whose developing brains are sensitive to treatments such as chemotherapy, surgery, radiation, and high-dose steroids.
There is also a dose-response effect, with high-dose chemotherapy such as ablative regimens used for bone-marrow transplantation being associated with higher probability of cognitive problems.
Dr. Ahles noted that about two-thirds of adult survivors of childhood cancers develop chronic illnesses within 30 years of diagnosis, including cardiac and pulmonary disease, and diabetes and endocrine dysfunction.
“It turns out they’re also at higher risk for cognitive issues,” including white matter abnormalities and microvascular stroke, he said.
The population of survivors of brain tumors and childhood cancers is dwarfed, however, by the large and growing population of breast, colorectal, lung, and prostate cancer patients who are diagnosed every year and exposed to adjuvant therapies, he added.
Aging and cognitive reserve
Evidence from breast cancer studies has shown that about 20%-25% of patients have lower than expected cognitive functioning – based on age, education, occupation, and other factors – before they embark on adjuvant therapy.
“That’s actually a risk factor for posttreatment cognitive decline, so there’s something that’s already going on that’s disrupting the cognitive information-processing system before we even start adjuvant treatment that may be critically important in terms of their outcomes as survivors,” Dr. Ahles said.
A significant subset of women in longitudinal studies of breast cancer survivors – about 15%-30% – experience long-term posttreatment cognitive problems, making it imperative for researchers and clinicians to identify risk factors for persistent cognitive decline, he said.
There is evidence to suggest that cancer treatments may interplay with biologic factors at the cellular level to increase the risk for cognitive loss. For example, aging is associated with reduction in brain volume, decrease in white matter integrity, and decreases in vascularization and neurotransmitter activity.
The effects of age on the brain are attenuated, however, among patients with higher cognitive reserves, defined as a combination of innate and developed cognitive capacity. Cognitive reserve is influenced by a number of factors, including genetics, education, occupational attainment, and lifestyle.
High cognitive reserve has been associated with later onset of Alzheimer’s disease symptoms and smaller changes in cognitive function with normal aging or following a brain injury, Dr. Ahles noted.
In a longitudinal study of cognitive changes associated with adjuvant therapy for breast cancer, Dr. Ahles and colleagues found that both age and pretreatment cognitive reserve were related to posttreatment decline in processing speed in women exposed to chemotherapy, compared with those who did not have chemotherapy or with healthy controls. In addition, chemotherapy had a short-term impact on verbal ability. The authors found evidence to suggest the patterns they saw may be related to the combination of chemotherapy and tamoxifen.
Part of the difficulty of studying cognitive decline among older patients is the higher prevalence of changes associated with aging. Dr. Ahles pointed to a French longitudinal study of women over 65 being treated for breast cancer, in which investigators found that 41% of the study population had cognitive impairment before starting on adjuvant therapy.
Older adults may be more frail, with diminished biological reserves and lower resistance to stressors caused by “cumulative declines across a variety of physiological systems making you more vulnerable to adverse events,” Dr. Ahles said.
Aging and genetics
Genes associated with cognitive aging are also risk factors for posttreatment cognitive decline, notably the genetic variants of APOE, including the epsilon 4 (APOE-e4) allele linked to increased risk for early-onset Alzheimer’s disease.
Dr. Ahles and colleagues had previously shown that APOE-e4 may be a biomarker for increased risk for chemotherapy-induced cognitive decline. The adverse effects of APOE-e4 appear to be mitigated somewhat by smoking, because it may correct for a deficit in nicotinic receptor density and dopamine levels in carriers.
Another genetic factor linked to postchemotherapy cognitive decline is the Val158Met polymorphism of the gene encoding for Catechol-O-methyltransferase (COMT), an enzyme that degrades neurotransmitters such as dopamine. Patients with this polymorphism have rapid dopamine metabolism, resulting in reduced dopamine activity.
These findings point to potential molecular mechanisms for cognitive changes associated with chemotherapy, and suggest that therapies targeted at neurotransmitter systems may ameliorate the effect, Dr. Ahles said.
He noted that animal studies have shown that fluoxetine (Prozac) prevents deficits in behavior and hippocampal function associated with 5-fluourauracil (5-FU), and that nicotine patches have been shown to improve cognitive functioning in patients with mild cognitive impairment.
The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.
BOSTON – The risk for cognitive decline following cancer treatment varies by both cancer and therapy types, and can range from subtle changes to severe deficits, according to a researcher.
Patients who are older, have lower cognitive reserves, or have comorbidities such as cardiovascular disease or diabetes are at risk for cognitive problems following cancer treatment, said Tim A. Ahles, Ph.D., director of the Neurocognitive Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York.
“I think it’s important that we identify these modifiable risk factors for intervention, and some of the nonmodifiable risk factors that inform decision making,” he said at the Palliative Care in Oncology Symposium.
“When we talk about cognitive function, we’re really talking about how does cancer and cancer treatment impact on memory, concentration, executive function, or ability to multitask, the speed at which we process information,” he said.
Oncologists have known for decades that brain tumors and their treatment have a negative effect on cognitive function, particularly among children under 5 years of age, whose developing brains are sensitive to treatments such as chemotherapy, surgery, radiation, and high-dose steroids.
There is also a dose-response effect, with high-dose chemotherapy such as ablative regimens used for bone-marrow transplantation being associated with higher probability of cognitive problems.
Dr. Ahles noted that about two-thirds of adult survivors of childhood cancers develop chronic illnesses within 30 years of diagnosis, including cardiac and pulmonary disease, and diabetes and endocrine dysfunction.
“It turns out they’re also at higher risk for cognitive issues,” including white matter abnormalities and microvascular stroke, he said.
The population of survivors of brain tumors and childhood cancers is dwarfed, however, by the large and growing population of breast, colorectal, lung, and prostate cancer patients who are diagnosed every year and exposed to adjuvant therapies, he added.
Aging and cognitive reserve
Evidence from breast cancer studies has shown that about 20%-25% of patients have lower than expected cognitive functioning – based on age, education, occupation, and other factors – before they embark on adjuvant therapy.
“That’s actually a risk factor for posttreatment cognitive decline, so there’s something that’s already going on that’s disrupting the cognitive information-processing system before we even start adjuvant treatment that may be critically important in terms of their outcomes as survivors,” Dr. Ahles said.
A significant subset of women in longitudinal studies of breast cancer survivors – about 15%-30% – experience long-term posttreatment cognitive problems, making it imperative for researchers and clinicians to identify risk factors for persistent cognitive decline, he said.
There is evidence to suggest that cancer treatments may interplay with biologic factors at the cellular level to increase the risk for cognitive loss. For example, aging is associated with reduction in brain volume, decrease in white matter integrity, and decreases in vascularization and neurotransmitter activity.
The effects of age on the brain are attenuated, however, among patients with higher cognitive reserves, defined as a combination of innate and developed cognitive capacity. Cognitive reserve is influenced by a number of factors, including genetics, education, occupational attainment, and lifestyle.
High cognitive reserve has been associated with later onset of Alzheimer’s disease symptoms and smaller changes in cognitive function with normal aging or following a brain injury, Dr. Ahles noted.
In a longitudinal study of cognitive changes associated with adjuvant therapy for breast cancer, Dr. Ahles and colleagues found that both age and pretreatment cognitive reserve were related to posttreatment decline in processing speed in women exposed to chemotherapy, compared with those who did not have chemotherapy or with healthy controls. In addition, chemotherapy had a short-term impact on verbal ability. The authors found evidence to suggest the patterns they saw may be related to the combination of chemotherapy and tamoxifen.
Part of the difficulty of studying cognitive decline among older patients is the higher prevalence of changes associated with aging. Dr. Ahles pointed to a French longitudinal study of women over 65 being treated for breast cancer, in which investigators found that 41% of the study population had cognitive impairment before starting on adjuvant therapy.
Older adults may be more frail, with diminished biological reserves and lower resistance to stressors caused by “cumulative declines across a variety of physiological systems making you more vulnerable to adverse events,” Dr. Ahles said.
Aging and genetics
Genes associated with cognitive aging are also risk factors for posttreatment cognitive decline, notably the genetic variants of APOE, including the epsilon 4 (APOE-e4) allele linked to increased risk for early-onset Alzheimer’s disease.
Dr. Ahles and colleagues had previously shown that APOE-e4 may be a biomarker for increased risk for chemotherapy-induced cognitive decline. The adverse effects of APOE-e4 appear to be mitigated somewhat by smoking, because it may correct for a deficit in nicotinic receptor density and dopamine levels in carriers.
Another genetic factor linked to postchemotherapy cognitive decline is the Val158Met polymorphism of the gene encoding for Catechol-O-methyltransferase (COMT), an enzyme that degrades neurotransmitters such as dopamine. Patients with this polymorphism have rapid dopamine metabolism, resulting in reduced dopamine activity.
These findings point to potential molecular mechanisms for cognitive changes associated with chemotherapy, and suggest that therapies targeted at neurotransmitter systems may ameliorate the effect, Dr. Ahles said.
He noted that animal studies have shown that fluoxetine (Prozac) prevents deficits in behavior and hippocampal function associated with 5-fluourauracil (5-FU), and that nicotine patches have been shown to improve cognitive functioning in patients with mild cognitive impairment.
The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.
Key clinical point: Cognitive decline following chemotherapy may be an interplay of aging and drug-induced molecular changes.
Major finding: An estimated 20%-25% of women in breast cancer studies have lower than predicted cognitive function before starting chemotherapy.
Data source: Review of evidence on the association between cancer chemotherapy and cognitive decline.
Disclosures: Dr. Ahles’ work is supported by Memorial-Sloan Kettering Cancer Center. He reported having no relevant disclosures.
ROR score aids prognosis after 5 years on tamoxifen
The risk of recurrence (ROR) score provides clinically meaningful prognostic information after postmenopausal women with early-stage breast cancer complete 5 years of tamoxifen therapy, according to a report published online Oct. 27 in Journal of Clinical Oncology.
The ROR score is derived from a quantitative assessment of a tumor’s expression of 46 genes related to breast cancer plus a measure of the tumor’s size. In this study, it was added to the Clinical Treatment Score, a standard prognostic tool that takes into account nodal status, tumor size and grade, patient age, and treatment modalities, said Ivana Sestak, Ph.D., of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University, London, and her associates.
To examine the usefulness of the ROR score in assessing risk for late recurrence of breast cancer, researchers analyzed combined data from two large clinical trials involving 2,137 postmenopausal women with early-stage hormone receptor–positive breast cancer who received 5 years of endocrine therapy but no chemotherapy and were followed for a further 5 years. There were 148 distant recurrences during that time.
Women classified by ROR score as high risk were 6.9 times more likely to develop a late recurrence than were those classified as low risk, and women classified by ROR score as intermediate risk were 3.3 times more likely to develop a late recurrence. The addition of ROR score to the Clinical Treatment Score reclassified 32 women as high risk, and those women did go on to develop a late recurrence. Similarly, adding to ROR score to the Clinical Treatment Score reclassified three women as low risk, and those women did not go on to develop a late recurrence, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.55.6894]).
In particular, the ROR score was helpful in assigning a “low-risk” designation to women who had node-negative and node-negative/HER2-negative disease, even though some of them had large tumors. These women could safely be spared from further endocrine therapy. Likewise, the ROR score was helpful in identifying women at high risk of recurrence who may wish to extend endocrine therapy beyond 5 years, Dr. Sestak and her associates said.
The risk of recurrence (ROR) score provides clinically meaningful prognostic information after postmenopausal women with early-stage breast cancer complete 5 years of tamoxifen therapy, according to a report published online Oct. 27 in Journal of Clinical Oncology.
The ROR score is derived from a quantitative assessment of a tumor’s expression of 46 genes related to breast cancer plus a measure of the tumor’s size. In this study, it was added to the Clinical Treatment Score, a standard prognostic tool that takes into account nodal status, tumor size and grade, patient age, and treatment modalities, said Ivana Sestak, Ph.D., of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University, London, and her associates.
To examine the usefulness of the ROR score in assessing risk for late recurrence of breast cancer, researchers analyzed combined data from two large clinical trials involving 2,137 postmenopausal women with early-stage hormone receptor–positive breast cancer who received 5 years of endocrine therapy but no chemotherapy and were followed for a further 5 years. There were 148 distant recurrences during that time.
Women classified by ROR score as high risk were 6.9 times more likely to develop a late recurrence than were those classified as low risk, and women classified by ROR score as intermediate risk were 3.3 times more likely to develop a late recurrence. The addition of ROR score to the Clinical Treatment Score reclassified 32 women as high risk, and those women did go on to develop a late recurrence. Similarly, adding to ROR score to the Clinical Treatment Score reclassified three women as low risk, and those women did not go on to develop a late recurrence, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.55.6894]).
In particular, the ROR score was helpful in assigning a “low-risk” designation to women who had node-negative and node-negative/HER2-negative disease, even though some of them had large tumors. These women could safely be spared from further endocrine therapy. Likewise, the ROR score was helpful in identifying women at high risk of recurrence who may wish to extend endocrine therapy beyond 5 years, Dr. Sestak and her associates said.
The risk of recurrence (ROR) score provides clinically meaningful prognostic information after postmenopausal women with early-stage breast cancer complete 5 years of tamoxifen therapy, according to a report published online Oct. 27 in Journal of Clinical Oncology.
The ROR score is derived from a quantitative assessment of a tumor’s expression of 46 genes related to breast cancer plus a measure of the tumor’s size. In this study, it was added to the Clinical Treatment Score, a standard prognostic tool that takes into account nodal status, tumor size and grade, patient age, and treatment modalities, said Ivana Sestak, Ph.D., of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University, London, and her associates.
To examine the usefulness of the ROR score in assessing risk for late recurrence of breast cancer, researchers analyzed combined data from two large clinical trials involving 2,137 postmenopausal women with early-stage hormone receptor–positive breast cancer who received 5 years of endocrine therapy but no chemotherapy and were followed for a further 5 years. There were 148 distant recurrences during that time.
Women classified by ROR score as high risk were 6.9 times more likely to develop a late recurrence than were those classified as low risk, and women classified by ROR score as intermediate risk were 3.3 times more likely to develop a late recurrence. The addition of ROR score to the Clinical Treatment Score reclassified 32 women as high risk, and those women did go on to develop a late recurrence. Similarly, adding to ROR score to the Clinical Treatment Score reclassified three women as low risk, and those women did not go on to develop a late recurrence, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.55.6894]).
In particular, the ROR score was helpful in assigning a “low-risk” designation to women who had node-negative and node-negative/HER2-negative disease, even though some of them had large tumors. These women could safely be spared from further endocrine therapy. Likewise, the ROR score was helpful in identifying women at high risk of recurrence who may wish to extend endocrine therapy beyond 5 years, Dr. Sestak and her associates said.
Key clinical point: The ROR score adds meaningful prognostic information 5-10 years after patients complete a 5-year course of tamoxifen for breast cancer.
Major finding: Women classified by ROR score as high risk were 6.9 times more likely to develop a late recurrence, and women classified by ROR score as intermediate risk were 3.3 times more likely to develop a late recurrence, compared with those classified as low risk.
Data source: A secondary, combined analysis of data from two large breast cancer trials involving 2,137 women followed for an additional 5 years after completing a 5-year course of tamoxifen.
Disclosures: This study was supported by Breakthrough Breast Cancer, the National Institute for Health Research Biomedical Research Centre at Royal Marsden Hospital, and Cancer Research U.K. Dr. Sestak reported having no financial conflicts of interest; her associates reported ties to numerous industry sources.
None of 19 potential biomarkers predicted pertuzumab response
None of the 19 potential biomarkers assessed in an exploratory study were found to help select which patients with HER2-positive metastatic breast cancer would benefit most from treatment with the monoclonal anti-HER2 antibody pertuzumab – other than the HER2 biomarker already in use for that purpose, according to a report published online Oct. 27 in Journal of Clinical Oncology.
Even though anti-HER2 therapies for metastatic breast cancer have been in use for more than 15 years, HER2 status itself remains the only marker of sensitivity to those agents, and it is an imperfect one. “We therefore aimed to explore within the HER2-positive patient population whether subgroups that derive differential progression-free survival or overall survival benefit from HER2-targeted treatment can be identified based on biomarker profiles,” said Dr. José Baselga, physician in chief and chief medical officer at Memorial Sloan Kettering Cancer Center, New York, and his associates.
They analyzed tumor, serum, and whole blood samples from 808 participants in a phase III randomized clinical trial assessing response to pertuzumab and trastuzumab therapy. These patients had locally recurrent nonresectable or metastatic breast cancer and had not received any chemotherapy. Each tissue sample was tested using a panel of 19 potentially useful biomarkers thought to be involved in either resistance to HER2-targeted agents or regulation of HER2-signaling pathways, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2013.54.5384]).
None of the biomarkers were found to correlate with treatment response, as measured by the patients’ progression-free and overall survival. One biomarker, a mutation in the PIK3CA gene, appeared to identify tumors that would not respond well to pertuzumab even though they expressed HER2, but further study of this possible association is needed, Dr. Baselga and his associates said.
None of the 19 potential biomarkers assessed in an exploratory study were found to help select which patients with HER2-positive metastatic breast cancer would benefit most from treatment with the monoclonal anti-HER2 antibody pertuzumab – other than the HER2 biomarker already in use for that purpose, according to a report published online Oct. 27 in Journal of Clinical Oncology.
Even though anti-HER2 therapies for metastatic breast cancer have been in use for more than 15 years, HER2 status itself remains the only marker of sensitivity to those agents, and it is an imperfect one. “We therefore aimed to explore within the HER2-positive patient population whether subgroups that derive differential progression-free survival or overall survival benefit from HER2-targeted treatment can be identified based on biomarker profiles,” said Dr. José Baselga, physician in chief and chief medical officer at Memorial Sloan Kettering Cancer Center, New York, and his associates.
They analyzed tumor, serum, and whole blood samples from 808 participants in a phase III randomized clinical trial assessing response to pertuzumab and trastuzumab therapy. These patients had locally recurrent nonresectable or metastatic breast cancer and had not received any chemotherapy. Each tissue sample was tested using a panel of 19 potentially useful biomarkers thought to be involved in either resistance to HER2-targeted agents or regulation of HER2-signaling pathways, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2013.54.5384]).
None of the biomarkers were found to correlate with treatment response, as measured by the patients’ progression-free and overall survival. One biomarker, a mutation in the PIK3CA gene, appeared to identify tumors that would not respond well to pertuzumab even though they expressed HER2, but further study of this possible association is needed, Dr. Baselga and his associates said.
None of the 19 potential biomarkers assessed in an exploratory study were found to help select which patients with HER2-positive metastatic breast cancer would benefit most from treatment with the monoclonal anti-HER2 antibody pertuzumab – other than the HER2 biomarker already in use for that purpose, according to a report published online Oct. 27 in Journal of Clinical Oncology.
Even though anti-HER2 therapies for metastatic breast cancer have been in use for more than 15 years, HER2 status itself remains the only marker of sensitivity to those agents, and it is an imperfect one. “We therefore aimed to explore within the HER2-positive patient population whether subgroups that derive differential progression-free survival or overall survival benefit from HER2-targeted treatment can be identified based on biomarker profiles,” said Dr. José Baselga, physician in chief and chief medical officer at Memorial Sloan Kettering Cancer Center, New York, and his associates.
They analyzed tumor, serum, and whole blood samples from 808 participants in a phase III randomized clinical trial assessing response to pertuzumab and trastuzumab therapy. These patients had locally recurrent nonresectable or metastatic breast cancer and had not received any chemotherapy. Each tissue sample was tested using a panel of 19 potentially useful biomarkers thought to be involved in either resistance to HER2-targeted agents or regulation of HER2-signaling pathways, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2013.54.5384]).
None of the biomarkers were found to correlate with treatment response, as measured by the patients’ progression-free and overall survival. One biomarker, a mutation in the PIK3CA gene, appeared to identify tumors that would not respond well to pertuzumab even though they expressed HER2, but further study of this possible association is needed, Dr. Baselga and his associates said.
Key clinical point: None of the 19 biomarkers assessed in an exploratory genetic study were found to aid in patient selection for pertuzumab-based treatment of metastatic breast cancer,
Major finding: None of the biomarkers were found to correlate with treatment response, as measured by the patients’ progression-free and overall survival.
Data source: A prospective laboratory assessment of 19 potential biomarkers from 808 tumor and serum samples taken from participants in a clinical trial assessing treatment response to pertuzumab.
Disclosures: The clinical trial on which this study was based was sponsored by Hoffmann-LaRoche, which also participated in the study design, data interpretation, and the writing and publication of the report. Dr. Baselga reported serving as a consultant for Genentech and Novartis; his associates reported ties to numerous industry sources.
VIDEO: SERMs move beyond osteoporosis, breast cancer prevention
HONOLULU– Uses for selective estrogen receptor modulators have grown beyond prevention of breast cancer or osteoporosis to treatment of postmenopausal symptoms.
Dr. Cynthia Stuenkel spoke about selective estrogen receptor modifiers (SERMs) and menopause in a keynote address at the annual meeting of the American Society for Reproductive Medicine.
In a video interview, Dr. Stuenkel talks about two of the newer SERM options – ospemifene for dyspareunia and a combination of the SERM bazedoxifene and conjugated equine estrogens that’s available outside of the United States to treat vasomotor symptoms or for prevention of bone loss.
These new tools expand clinical options – but, as with any new therapy – longer and larger studies of the newer agents are needed to more carefully assess long-term safety, said Dr. Stuenkel of the University of California, San Diego.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
HONOLULU– Uses for selective estrogen receptor modulators have grown beyond prevention of breast cancer or osteoporosis to treatment of postmenopausal symptoms.
Dr. Cynthia Stuenkel spoke about selective estrogen receptor modifiers (SERMs) and menopause in a keynote address at the annual meeting of the American Society for Reproductive Medicine.
In a video interview, Dr. Stuenkel talks about two of the newer SERM options – ospemifene for dyspareunia and a combination of the SERM bazedoxifene and conjugated equine estrogens that’s available outside of the United States to treat vasomotor symptoms or for prevention of bone loss.
These new tools expand clinical options – but, as with any new therapy – longer and larger studies of the newer agents are needed to more carefully assess long-term safety, said Dr. Stuenkel of the University of California, San Diego.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
HONOLULU– Uses for selective estrogen receptor modulators have grown beyond prevention of breast cancer or osteoporosis to treatment of postmenopausal symptoms.
Dr. Cynthia Stuenkel spoke about selective estrogen receptor modifiers (SERMs) and menopause in a keynote address at the annual meeting of the American Society for Reproductive Medicine.
In a video interview, Dr. Stuenkel talks about two of the newer SERM options – ospemifene for dyspareunia and a combination of the SERM bazedoxifene and conjugated equine estrogens that’s available outside of the United States to treat vasomotor symptoms or for prevention of bone loss.
These new tools expand clinical options – but, as with any new therapy – longer and larger studies of the newer agents are needed to more carefully assess long-term safety, said Dr. Stuenkel of the University of California, San Diego.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
EXPERT ANALYSIS FROM 2014 ASRM
Adjuvant ovarian suppression impairs QOL in women with breast cancer
For premenopausal women who have undergone definitive surgery for node-negative invasive breast cancer, adjuvant therapy with tamoxifen plus ovarian function suppression significantly impairs quality of life, compared with tamoxifen alone, according to a report published online October 27 in Journal of Clinical Oncology.
The role of ovarian function suppression in this setting remains uncertain because most studies examining the issue have been relatively short (2 years or less) and have included patients undergoing cytotoxic chemotherapy, which makes it difficult to tease out which drugs produce which outcomes of interest. In contrast, this open-label, phase III, randomized trial by the Eastern Cooperative Oncology Group had a mean follow-up of 10 years, and it included only women with hormone receptor–positive tumors measuring 3 cm or less who received no adjuvant chemotherapy, said Dr. Amye J. Tevaawerk of the University of Wisconsin, Madison, and her associates.
The 345 study participants were randomly assigned to receive either tamoxifen plus ovarian function suppression via goserelin, leuprolide, surgical ablation, or radiation ablation (174 women) or tamoxifen alone (171 women). The median age at baseline was 45 years (range, 26-55 years). The trial was designed to compare multiple outcomes, including disease-free survival, overall survival, and quality of life, but it was terminated early because of slow accrual and ultimately was only powered to detect differences in quality of life (QOL).
Throughout follow-up, women who received tamoxifen plus ovarian suppression reported inferior health-related QOL as measured by the Functional Assessment of Cancer Therapy – General (FACT-G) and the Functional Assessment of Cancer Therapy – Breast (FACT-B). They had more menopausal symptoms and lower levels of sexual function than women who received tamoxifen alone, regardless of patient age or race, tumor hormone-receptor status, tumor size, or type of surgical procedure. The differences between the two study groups were both statistically significant and clinically meaningful, Dr. Tevaawerk and her associates said (J. Clin. Oncol. 2014 October 27 [doi:10.1200/JCO.2014.55.6993]).
The negative impact of ovarian suppression gradually diminished after 3 years, most likely because increasing numbers of women receiving tamoxifen alone reached menopause. “Our results suggest that [studies with] durations of less than 3 years fail to capture the adverse effect peak and the health-related QOL nadir from ovarian function suppression,” the investigators said. “Given these data and in the absence of definitive data for improvement in disease-free survival or overall survival with ovarian function suppression, the American Society of Clinical Oncology guidelines are appropriately cautious about adding ovarian function suppression to tamoxifen,” they noted.
For premenopausal women who have undergone definitive surgery for node-negative invasive breast cancer, adjuvant therapy with tamoxifen plus ovarian function suppression significantly impairs quality of life, compared with tamoxifen alone, according to a report published online October 27 in Journal of Clinical Oncology.
The role of ovarian function suppression in this setting remains uncertain because most studies examining the issue have been relatively short (2 years or less) and have included patients undergoing cytotoxic chemotherapy, which makes it difficult to tease out which drugs produce which outcomes of interest. In contrast, this open-label, phase III, randomized trial by the Eastern Cooperative Oncology Group had a mean follow-up of 10 years, and it included only women with hormone receptor–positive tumors measuring 3 cm or less who received no adjuvant chemotherapy, said Dr. Amye J. Tevaawerk of the University of Wisconsin, Madison, and her associates.
The 345 study participants were randomly assigned to receive either tamoxifen plus ovarian function suppression via goserelin, leuprolide, surgical ablation, or radiation ablation (174 women) or tamoxifen alone (171 women). The median age at baseline was 45 years (range, 26-55 years). The trial was designed to compare multiple outcomes, including disease-free survival, overall survival, and quality of life, but it was terminated early because of slow accrual and ultimately was only powered to detect differences in quality of life (QOL).
Throughout follow-up, women who received tamoxifen plus ovarian suppression reported inferior health-related QOL as measured by the Functional Assessment of Cancer Therapy – General (FACT-G) and the Functional Assessment of Cancer Therapy – Breast (FACT-B). They had more menopausal symptoms and lower levels of sexual function than women who received tamoxifen alone, regardless of patient age or race, tumor hormone-receptor status, tumor size, or type of surgical procedure. The differences between the two study groups were both statistically significant and clinically meaningful, Dr. Tevaawerk and her associates said (J. Clin. Oncol. 2014 October 27 [doi:10.1200/JCO.2014.55.6993]).
The negative impact of ovarian suppression gradually diminished after 3 years, most likely because increasing numbers of women receiving tamoxifen alone reached menopause. “Our results suggest that [studies with] durations of less than 3 years fail to capture the adverse effect peak and the health-related QOL nadir from ovarian function suppression,” the investigators said. “Given these data and in the absence of definitive data for improvement in disease-free survival or overall survival with ovarian function suppression, the American Society of Clinical Oncology guidelines are appropriately cautious about adding ovarian function suppression to tamoxifen,” they noted.
For premenopausal women who have undergone definitive surgery for node-negative invasive breast cancer, adjuvant therapy with tamoxifen plus ovarian function suppression significantly impairs quality of life, compared with tamoxifen alone, according to a report published online October 27 in Journal of Clinical Oncology.
The role of ovarian function suppression in this setting remains uncertain because most studies examining the issue have been relatively short (2 years or less) and have included patients undergoing cytotoxic chemotherapy, which makes it difficult to tease out which drugs produce which outcomes of interest. In contrast, this open-label, phase III, randomized trial by the Eastern Cooperative Oncology Group had a mean follow-up of 10 years, and it included only women with hormone receptor–positive tumors measuring 3 cm or less who received no adjuvant chemotherapy, said Dr. Amye J. Tevaawerk of the University of Wisconsin, Madison, and her associates.
The 345 study participants were randomly assigned to receive either tamoxifen plus ovarian function suppression via goserelin, leuprolide, surgical ablation, or radiation ablation (174 women) or tamoxifen alone (171 women). The median age at baseline was 45 years (range, 26-55 years). The trial was designed to compare multiple outcomes, including disease-free survival, overall survival, and quality of life, but it was terminated early because of slow accrual and ultimately was only powered to detect differences in quality of life (QOL).
Throughout follow-up, women who received tamoxifen plus ovarian suppression reported inferior health-related QOL as measured by the Functional Assessment of Cancer Therapy – General (FACT-G) and the Functional Assessment of Cancer Therapy – Breast (FACT-B). They had more menopausal symptoms and lower levels of sexual function than women who received tamoxifen alone, regardless of patient age or race, tumor hormone-receptor status, tumor size, or type of surgical procedure. The differences between the two study groups were both statistically significant and clinically meaningful, Dr. Tevaawerk and her associates said (J. Clin. Oncol. 2014 October 27 [doi:10.1200/JCO.2014.55.6993]).
The negative impact of ovarian suppression gradually diminished after 3 years, most likely because increasing numbers of women receiving tamoxifen alone reached menopause. “Our results suggest that [studies with] durations of less than 3 years fail to capture the adverse effect peak and the health-related QOL nadir from ovarian function suppression,” the investigators said. “Given these data and in the absence of definitive data for improvement in disease-free survival or overall survival with ovarian function suppression, the American Society of Clinical Oncology guidelines are appropriately cautious about adding ovarian function suppression to tamoxifen,” they noted.
Key clinical point: Adding ovarian function suppression to standard tamoxifen in premenopausal women with early breast cancer definitely impairs QOL.
Major finding: Women who received tamoxifen plus ovarian suppression reported inferior health-related QOL, with more menopausal symptoms and lower levels of sexual function, than women who received tamoxifen alone, regardless of patient age or race, tumor hormone receptor status, tumor size, or type of surgical procedure.
Data source: An open-label, phase III, randomized, controlled trial comparing adjuvant tamoxifen alone against tamoxifen plus ovarian function suppression in 345 premenopausal women with early-stage breast cancer.
Disclosures: This Eastern Cooperative Oncology Group study was supported in part by Public Health Service grants from the National Cancer Institute and by the National Institutes of Health National Center for Advancing Translational Sciences. Dr. Tevaawerk and her associates reported having no financial conflicts of interest.
Hippocampus-sparing brain radiotherapy preserves memory, QOL
For cancer patients who have multiple brain metastases, tailoring whole-brain radiotherapy so that it avoids the hippocampus preserves memory and quality of life for at least 6 months, according to a report published online Oct. 27 in the Journal of Clinical Oncology.
Injury to the compartment of neural stem cells located in the subgranular zone of the hippocampal dentate gyrus is thought to suppress the formation of new memory and to impair recall, and injury to this region by relatively low doses of radiotherapy is thought to account for radiation-induced early cognitive decline. Researchers performed a multicenter phase II trial to determine whether sparing this region would prevent such cognitive decline. They assessed 100 patients who had brain metastases of nonhematopoietic malignancies and underwent irradiation of the whole-brain parenchyma minus the “hippocampal avoidance regions” that had been designated using advanced imaging techniques, said Dr. Vinai Gondi of the Cadence Brain Tumor Center and CDH Proton Center, Warrenville, Ill., and his associates.
The study participants underwent cognitive assessment at baseline and at regular intervals following radiotherapy, as well as assessment of health-related quality of life. Their results were compared with those of 208 historical control subjects who had received standard whole-brain radiotherapy without hippocampal avoidance in an unrelated clinical trial. The radiation-sparing technique, which reduced the mean dose to the neural stem compartment by an estimated 80%, produced significant memory preservation that persisted for up to 6 months of follow-up. The mean probability of cognitive deterioration at 4 months was only 7%, compared with 30% in the historical control group.
The hippocampal-sparing technique also preserved physical, social/family, emotional, and functional well-being, as assessed by the patient and his or her family, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.57.2909]).
The risk that metastases would develop in the nonradiated hippocampus was considered low, as only three patients (4.5%) developed such metastases. Previously, investigators have predicted that the risk would be closer to 10%, but they appear to have overestimated the actual risk, Dr. Gondi and his associates said.
These promising results require further validation in phase III trials. Studies are now underway to assess whether further reducing the radiation dose to the hippocampal area may improve outcomes even more, and future studies also are being planned to assess whether hippocampal avoidance prevents longer-term cognitive decline, beyond the 6-month mark established in this study, the investigators added.
This study was supported by the National Cancer Institute’s Radiation Therapy Oncology Group and Community Clinical Oncology Program. Dr. Gondi reported having no financial disclosures; his associates reported numerous ties to industry sources.
The findings of this phase II study need to be replicated and expanded upon before this innovative treatment approach can be offered to patients.
To justify the increased cost, time, and effort involved in hippocampal-avoidance whole-brain radiotherapy, it may be necessary to prove that the technique improves survival, not just QOL. And the influence of factors such as the number and size of brain metastases, extracranial disease status, and prognostic assessment scores should be addressed in future studies, to narrow down which patients will benefit most from the therapy.
Dr. John H. Suh is in the department of radiation oncology at the Cleveland Clinic. He reported receiving honoraria and serving as a consultant or adviser to Varian Medical Systems. Dr. Suh made these remarks in an editorial accompanying Dr. Gondi’s report (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.58.4367]).
The findings of this phase II study need to be replicated and expanded upon before this innovative treatment approach can be offered to patients.
To justify the increased cost, time, and effort involved in hippocampal-avoidance whole-brain radiotherapy, it may be necessary to prove that the technique improves survival, not just QOL. And the influence of factors such as the number and size of brain metastases, extracranial disease status, and prognostic assessment scores should be addressed in future studies, to narrow down which patients will benefit most from the therapy.
Dr. John H. Suh is in the department of radiation oncology at the Cleveland Clinic. He reported receiving honoraria and serving as a consultant or adviser to Varian Medical Systems. Dr. Suh made these remarks in an editorial accompanying Dr. Gondi’s report (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.58.4367]).
The findings of this phase II study need to be replicated and expanded upon before this innovative treatment approach can be offered to patients.
To justify the increased cost, time, and effort involved in hippocampal-avoidance whole-brain radiotherapy, it may be necessary to prove that the technique improves survival, not just QOL. And the influence of factors such as the number and size of brain metastases, extracranial disease status, and prognostic assessment scores should be addressed in future studies, to narrow down which patients will benefit most from the therapy.
Dr. John H. Suh is in the department of radiation oncology at the Cleveland Clinic. He reported receiving honoraria and serving as a consultant or adviser to Varian Medical Systems. Dr. Suh made these remarks in an editorial accompanying Dr. Gondi’s report (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.58.4367]).
For cancer patients who have multiple brain metastases, tailoring whole-brain radiotherapy so that it avoids the hippocampus preserves memory and quality of life for at least 6 months, according to a report published online Oct. 27 in the Journal of Clinical Oncology.
Injury to the compartment of neural stem cells located in the subgranular zone of the hippocampal dentate gyrus is thought to suppress the formation of new memory and to impair recall, and injury to this region by relatively low doses of radiotherapy is thought to account for radiation-induced early cognitive decline. Researchers performed a multicenter phase II trial to determine whether sparing this region would prevent such cognitive decline. They assessed 100 patients who had brain metastases of nonhematopoietic malignancies and underwent irradiation of the whole-brain parenchyma minus the “hippocampal avoidance regions” that had been designated using advanced imaging techniques, said Dr. Vinai Gondi of the Cadence Brain Tumor Center and CDH Proton Center, Warrenville, Ill., and his associates.
The study participants underwent cognitive assessment at baseline and at regular intervals following radiotherapy, as well as assessment of health-related quality of life. Their results were compared with those of 208 historical control subjects who had received standard whole-brain radiotherapy without hippocampal avoidance in an unrelated clinical trial. The radiation-sparing technique, which reduced the mean dose to the neural stem compartment by an estimated 80%, produced significant memory preservation that persisted for up to 6 months of follow-up. The mean probability of cognitive deterioration at 4 months was only 7%, compared with 30% in the historical control group.
The hippocampal-sparing technique also preserved physical, social/family, emotional, and functional well-being, as assessed by the patient and his or her family, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.57.2909]).
The risk that metastases would develop in the nonradiated hippocampus was considered low, as only three patients (4.5%) developed such metastases. Previously, investigators have predicted that the risk would be closer to 10%, but they appear to have overestimated the actual risk, Dr. Gondi and his associates said.
These promising results require further validation in phase III trials. Studies are now underway to assess whether further reducing the radiation dose to the hippocampal area may improve outcomes even more, and future studies also are being planned to assess whether hippocampal avoidance prevents longer-term cognitive decline, beyond the 6-month mark established in this study, the investigators added.
This study was supported by the National Cancer Institute’s Radiation Therapy Oncology Group and Community Clinical Oncology Program. Dr. Gondi reported having no financial disclosures; his associates reported numerous ties to industry sources.
For cancer patients who have multiple brain metastases, tailoring whole-brain radiotherapy so that it avoids the hippocampus preserves memory and quality of life for at least 6 months, according to a report published online Oct. 27 in the Journal of Clinical Oncology.
Injury to the compartment of neural stem cells located in the subgranular zone of the hippocampal dentate gyrus is thought to suppress the formation of new memory and to impair recall, and injury to this region by relatively low doses of radiotherapy is thought to account for radiation-induced early cognitive decline. Researchers performed a multicenter phase II trial to determine whether sparing this region would prevent such cognitive decline. They assessed 100 patients who had brain metastases of nonhematopoietic malignancies and underwent irradiation of the whole-brain parenchyma minus the “hippocampal avoidance regions” that had been designated using advanced imaging techniques, said Dr. Vinai Gondi of the Cadence Brain Tumor Center and CDH Proton Center, Warrenville, Ill., and his associates.
The study participants underwent cognitive assessment at baseline and at regular intervals following radiotherapy, as well as assessment of health-related quality of life. Their results were compared with those of 208 historical control subjects who had received standard whole-brain radiotherapy without hippocampal avoidance in an unrelated clinical trial. The radiation-sparing technique, which reduced the mean dose to the neural stem compartment by an estimated 80%, produced significant memory preservation that persisted for up to 6 months of follow-up. The mean probability of cognitive deterioration at 4 months was only 7%, compared with 30% in the historical control group.
The hippocampal-sparing technique also preserved physical, social/family, emotional, and functional well-being, as assessed by the patient and his or her family, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2014.57.2909]).
The risk that metastases would develop in the nonradiated hippocampus was considered low, as only three patients (4.5%) developed such metastases. Previously, investigators have predicted that the risk would be closer to 10%, but they appear to have overestimated the actual risk, Dr. Gondi and his associates said.
These promising results require further validation in phase III trials. Studies are now underway to assess whether further reducing the radiation dose to the hippocampal area may improve outcomes even more, and future studies also are being planned to assess whether hippocampal avoidance prevents longer-term cognitive decline, beyond the 6-month mark established in this study, the investigators added.
This study was supported by the National Cancer Institute’s Radiation Therapy Oncology Group and Community Clinical Oncology Program. Dr. Gondi reported having no financial disclosures; his associates reported numerous ties to industry sources.
Key clinical point: Whole-brain radiotherapy that spares the hippocampal neural stem cell compartment preserves memory and QOL in cancer patients with brain metastases.
Major finding: The mean probability of cognitive deterioration at 4 months was only 7% in patients who underwent hippocampus-sparing brain radiotherapy, compared with 30% in a historical control group.
Data source: A multicenter phase II study comparing cognitive function and QOL between 100 patients with brain metastases who had hippocampus-sparing radiotherapy and 208 historical control subjects who had standard whole-brain radiotherapy.
Disclosures: This study was supported by the National Cancer Institute’s Radiation Therapy Oncology Group and Community Clinical Oncology Program. Dr. Gondi reported having no financial disclosures; his associates reported numerous ties to industry sources.
Delivering on the promise of cancer biomarkers in the clinic
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Click on the PDF icon at the top of this introduction to read the full article.
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JCSO 2014;12:381-388
Weight change associated with third-generation adjuvant chemotherapy in breast cancer patients
Methods We retrospectively analyzed the mean percentage weight change during the first year after breast cancer diagnosis in 246 patients at West Virginia University during September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise comparisons were used to assess the influence of age, histology, stage, ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities received on the percentage weight change. Kaplan-Meier method with log-rank test was used to evaluate recurrence-free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free patients were censored at last follow-up.
Results Mean weight gain was 0.39% (SD, 0.40) of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal status was the only factor associated with significant weight gain (+1.67% vs -0.10% for postmenopausal patients; P = .02). Stages ≥ III was associated with significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II; P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs 0.91; P = .19). There was no significant change in weight relative to other factors.
Conclusion Our study in patients receiving third-generation adjuvant chemotherapy regimens did not show any significant change in percentage weight with chemotherapy. Premenopausal status was the only significant factor associated with weight gain. As expected, stage III or higher disease was associated with significant weight loss and lower RFS.
Click on the PDF icon at the top of this introduction to read the full article.
Methods We retrospectively analyzed the mean percentage weight change during the first year after breast cancer diagnosis in 246 patients at West Virginia University during September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise comparisons were used to assess the influence of age, histology, stage, ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities received on the percentage weight change. Kaplan-Meier method with log-rank test was used to evaluate recurrence-free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free patients were censored at last follow-up.
Results Mean weight gain was 0.39% (SD, 0.40) of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal status was the only factor associated with significant weight gain (+1.67% vs -0.10% for postmenopausal patients; P = .02). Stages ≥ III was associated with significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II; P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs 0.91; P = .19). There was no significant change in weight relative to other factors.
Conclusion Our study in patients receiving third-generation adjuvant chemotherapy regimens did not show any significant change in percentage weight with chemotherapy. Premenopausal status was the only significant factor associated with weight gain. As expected, stage III or higher disease was associated with significant weight loss and lower RFS.
Click on the PDF icon at the top of this introduction to read the full article.
Methods We retrospectively analyzed the mean percentage weight change during the first year after breast cancer diagnosis in 246 patients at West Virginia University during September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise comparisons were used to assess the influence of age, histology, stage, ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities received on the percentage weight change. Kaplan-Meier method with log-rank test was used to evaluate recurrence-free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free patients were censored at last follow-up.
Results Mean weight gain was 0.39% (SD, 0.40) of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal status was the only factor associated with significant weight gain (+1.67% vs -0.10% for postmenopausal patients; P = .02). Stages ≥ III was associated with significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II; P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs 0.91; P = .19). There was no significant change in weight relative to other factors.
Conclusion Our study in patients receiving third-generation adjuvant chemotherapy regimens did not show any significant change in percentage weight with chemotherapy. Premenopausal status was the only significant factor associated with weight gain. As expected, stage III or higher disease was associated with significant weight loss and lower RFS.
Click on the PDF icon at the top of this introduction to read the full article.
Breast cancer with brain metastases in pregnancy
Breast cancer during pregnancy is a therapeutic challenge. Evidence to guide management in metastatic breast cancer during pregnancy is limited, mainly because of a lack of randomized trials. Care needs to be individualized with interdisciplinary collaboration. We present the case of a young woman with HER2/neu overexpressed inflammatory breast cancer who became pregnant while on treatment, refused termination of pregnancy, and developed brain metastasis during the second trimester of pregnancy, posing a management dilemma.
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Breast cancer during pregnancy is a therapeutic challenge. Evidence to guide management in metastatic breast cancer during pregnancy is limited, mainly because of a lack of randomized trials. Care needs to be individualized with interdisciplinary collaboration. We present the case of a young woman with HER2/neu overexpressed inflammatory breast cancer who became pregnant while on treatment, refused termination of pregnancy, and developed brain metastasis during the second trimester of pregnancy, posing a management dilemma.
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Breast cancer during pregnancy is a therapeutic challenge. Evidence to guide management in metastatic breast cancer during pregnancy is limited, mainly because of a lack of randomized trials. Care needs to be individualized with interdisciplinary collaboration. We present the case of a young woman with HER2/neu overexpressed inflammatory breast cancer who became pregnant while on treatment, refused termination of pregnancy, and developed brain metastasis during the second trimester of pregnancy, posing a management dilemma.
Click on the PDF icon at the top of this introduction to read the full article.