Breast Cancer

SAN ANTONIO – Long-term upper-extremity pain and functional impairment following breast cancer surgery are reduced by an innovative physical therapy–centered surveillance program, according to a 5-year prospective study.

The program was developed at the breast care center of Walter Reed National Military Medical Center, Bethesda, Md. It begins with a preoperative patient interview and structured evaluation by a physical therapist. The assessment includes what physical therapists call an upper-quarter screen, which evaluates shoulder range of motion, strength, and arm volume. Self-reported pain, fatigue, function, and activity level are recorded.

At that time, the patient is also instructed in a home exercise program she is to start 2 weeks post surgery. These are simple range-of-motion exercises focused on forward flexion overhead; abduction; internal and external rotation of the glenohumeral joint; and scapular retraction, Nicole L. Stout explained at the San Antonio Breast Cancer Symposium.

The patient is subsequently seen by the physical therapist (in conjunction with her regular follow-up visits with an oncologist or surgeon) at 1, 3, 6, 9, 12, and 60 months post surgery. If upper-extremity dysfunction worsens, more intensive interventions are introduced.

The rationale for this prospective surveillance program lies in an understanding that the shoulder and arm impairments caused by breast cancer surgery and radiation therapy are typically subtle initially, but if left unidentified and uncorrected, they often progress to serious rotator cuff damage, "frozen" shoulder, and debilitating lymphedema, according to Ms. Stout, a civilian research physical therapist at the military center.

She had previously presented her 1-year prospective outcomes. This time around, she presented prospective 5-year follow-up data on 86 breast cancer patients who participated in the program. This is the first prospective cohort study in the United States to track breast cancer–related upper-extremity morbidity and functional outcomes for this long a time period.

The 12-month and 5-year visits included formal assessment of upper-extremity outcomes using the Harvard Alumni Activity Survey, the Upper Limb Disability Questionnaire, and the Short Form-36.

At 5 years, 11% of the women had stage I/II lymphedema and 38% had subclinical lymphedema (defined as less than 3% arm volume swelling as measured by a Perometer). These results compare favorably with those of published studies on lymphedema, which have reported long-term rates of stage I-III arm swelling in the 40%-60% range, she noted.

In all, 18% of patients reported arm numbness at 5 years, 17% noted shoulder pain, 3% had neck pain, and 1% had chest wall pain.

One-third of subjects reported fatigue of level 3 or more on a 10-point visual analog scale. Again, other investigators have documented long-term rates of clinically significant fatigue in the 50%-60% range.

At 5 years post surgery, patients demonstrated less impairment of physical activity than at preoperative baseline. At baseline, 33% had significant limitations in terms of carrying heavy objects, performing household chores, and other physical activities. After 5 years of prospective surveillance and tailored physical therapy, only 20% of patients had physical activity limitations.

However, 68% of patients reported experiencing some restrictions on their social activity at 5 years, and 52% experienced limitations on their recreational activities.

The study was funded by the medical center. Ms. Stout declared having no financial conflicts of interest.

SAN ANTONIO – Long-term upper-extremity pain and functional impairment following breast cancer surgery are reduced by an innovative physical therapy–centered surveillance program, according to a 5-year prospective study.

The program was developed at the breast care center of Walter Reed National Military Medical Center, Bethesda, Md. It begins with a preoperative patient interview and structured evaluation by a physical therapist. The assessment includes what physical therapists call an upper-quarter screen, which evaluates shoulder range of motion, strength, and arm volume. Self-reported pain, fatigue, function, and activity level are recorded.

At that time, the patient is also instructed in a home exercise program she is to start 2 weeks post surgery. These are simple range-of-motion exercises focused on forward flexion overhead; abduction; internal and external rotation of the glenohumeral joint; and scapular retraction, Nicole L. Stout explained at the San Antonio Breast Cancer Symposium.

The patient is subsequently seen by the physical therapist (in conjunction with her regular follow-up visits with an oncologist or surgeon) at 1, 3, 6, 9, 12, and 60 months post surgery. If upper-extremity dysfunction worsens, more intensive interventions are introduced.

The rationale for this prospective surveillance program lies in an understanding that the shoulder and arm impairments caused by breast cancer surgery and radiation therapy are typically subtle initially, but if left unidentified and uncorrected, they often progress to serious rotator cuff damage, "frozen" shoulder, and debilitating lymphedema, according to Ms. Stout, a civilian research physical therapist at the military center.

She had previously presented her 1-year prospective outcomes. This time around, she presented prospective 5-year follow-up data on 86 breast cancer patients who participated in the program. This is the first prospective cohort study in the United States to track breast cancer–related upper-extremity morbidity and functional outcomes for this long a time period.

The 12-month and 5-year visits included formal assessment of upper-extremity outcomes using the Harvard Alumni Activity Survey, the Upper Limb Disability Questionnaire, and the Short Form-36.

At 5 years, 11% of the women had stage I/II lymphedema and 38% had subclinical lymphedema (defined as less than 3% arm volume swelling as measured by a Perometer). These results compare favorably with those of published studies on lymphedema, which have reported long-term rates of stage I-III arm swelling in the 40%-60% range, she noted.

In all, 18% of patients reported arm numbness at 5 years, 17% noted shoulder pain, 3% had neck pain, and 1% had chest wall pain.

One-third of subjects reported fatigue of level 3 or more on a 10-point visual analog scale. Again, other investigators have documented long-term rates of clinically significant fatigue in the 50%-60% range.

At 5 years post surgery, patients demonstrated less impairment of physical activity than at preoperative baseline. At baseline, 33% had significant limitations in terms of carrying heavy objects, performing household chores, and other physical activities. After 5 years of prospective surveillance and tailored physical therapy, only 20% of patients had physical activity limitations.

However, 68% of patients reported experiencing some restrictions on their social activity at 5 years, and 52% experienced limitations on their recreational activities.

The study was funded by the medical center. Ms. Stout declared having no financial conflicts of interest.

SAN ANTONIO – Long-term upper-extremity pain and functional impairment following breast cancer surgery are reduced by an innovative physical therapy–centered surveillance program, according to a 5-year prospective study.

The program was developed at the breast care center of Walter Reed National Military Medical Center, Bethesda, Md. It begins with a preoperative patient interview and structured evaluation by a physical therapist. The assessment includes what physical therapists call an upper-quarter screen, which evaluates shoulder range of motion, strength, and arm volume. Self-reported pain, fatigue, function, and activity level are recorded.

At that time, the patient is also instructed in a home exercise program she is to start 2 weeks post surgery. These are simple range-of-motion exercises focused on forward flexion overhead; abduction; internal and external rotation of the glenohumeral joint; and scapular retraction, Nicole L. Stout explained at the San Antonio Breast Cancer Symposium.

The patient is subsequently seen by the physical therapist (in conjunction with her regular follow-up visits with an oncologist or surgeon) at 1, 3, 6, 9, 12, and 60 months post surgery. If upper-extremity dysfunction worsens, more intensive interventions are introduced.

The rationale for this prospective surveillance program lies in an understanding that the shoulder and arm impairments caused by breast cancer surgery and radiation therapy are typically subtle initially, but if left unidentified and uncorrected, they often progress to serious rotator cuff damage, "frozen" shoulder, and debilitating lymphedema, according to Ms. Stout, a civilian research physical therapist at the military center.

She had previously presented her 1-year prospective outcomes. This time around, she presented prospective 5-year follow-up data on 86 breast cancer patients who participated in the program. This is the first prospective cohort study in the United States to track breast cancer–related upper-extremity morbidity and functional outcomes for this long a time period.

The 12-month and 5-year visits included formal assessment of upper-extremity outcomes using the Harvard Alumni Activity Survey, the Upper Limb Disability Questionnaire, and the Short Form-36.

At 5 years, 11% of the women had stage I/II lymphedema and 38% had subclinical lymphedema (defined as less than 3% arm volume swelling as measured by a Perometer). These results compare favorably with those of published studies on lymphedema, which have reported long-term rates of stage I-III arm swelling in the 40%-60% range, she noted.

In all, 18% of patients reported arm numbness at 5 years, 17% noted shoulder pain, 3% had neck pain, and 1% had chest wall pain.

One-third of subjects reported fatigue of level 3 or more on a 10-point visual analog scale. Again, other investigators have documented long-term rates of clinically significant fatigue in the 50%-60% range.

At 5 years post surgery, patients demonstrated less impairment of physical activity than at preoperative baseline. At baseline, 33% had significant limitations in terms of carrying heavy objects, performing household chores, and other physical activities. After 5 years of prospective surveillance and tailored physical therapy, only 20% of patients had physical activity limitations.

However, 68% of patients reported experiencing some restrictions on their social activity at 5 years, and 52% experienced limitations on their recreational activities.

The study was funded by the medical center. Ms. Stout declared having no financial conflicts of interest.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Curbing colony-stimulating factor use at the start of dose-dense chemotherapy in Medicare patients with hormone receptor–positive breast cancer would save nearly $40 million per year in a population unlikely to gain meaningful benefit from such therapy, according to a new study.

The use of first-cycle colony-stimulating factor (CSF) therapy took off in 2002, Dr. Dawn L. Hershman told attendees at the San Antonio Breast Cancer Symposium. That was the year the benefits of dose-dense chemotherapy were reported, and pegfilgrastim (Neulasta), a granulocyte CSF that was easier to use than those previously available, received marketing approval from the Food and Drug Administration.

A new analysis of Medicare data shows that first-cycle use of CSFs in patients with stage I-III breast cancer jumped from 13% during 1998-2002 to 68% in 2002-2005, reported Dr. Hershman of Columbia University, New York.

In the last half-decade, however, multiple major studies have convincingly shown that the benefits of dose-dense chemotherapy with first-cycle CSFs are confined to breast cancer patients with hormone receptor–negative tumors, according to Dr. Hershman.

For example, one meta-analysis of studies comparing dose-dense to standard chemotherapy in 3,337 estrogen receptor–negative patients showed that dose-dense chemotherapy yielded a 29% reduction in recurrence risk and a 16% improvement in overall survival. In 1,344 estrogen receptor–positive patients, in contrast, dose-dense chemotherapy provided a nonsignificant 8% reduction in recurrence risk and no hint of a benefit in terms of overall survival (J. Natl. Cancer Inst. 2010;102:1845-54).

For the new study, Dr. Hershman and her coauthors identified 10,773 patients in a combined Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were over age 65 with stage I-III breast cancer diagnosed during 1998-2005, and who had at least one chemotherapy claim within 6 months of diagnosis. Of these, 5,266 had a CSF claim during therapy. First-cycle CSF use increased from 13% to 68% over the study period, and the use of pegfilgrastim jumped from 4% to 84%.

"We’re very quick in oncology to adopt, and we never pull back – even when there’s evidence against," Dr. Hershman said. "If we have to make decisions in terms of controlling costs, we shouldn’t be giving drugs that are costly and have no benefit."

Dr. Thomas J. Smith, chair of the session at which Dr. Hershman presented the new study, took the argument further, citing Dr. Hershman’s own earlier study suggesting that CSF therapy in elderly women may actually cause significant harm. In an analysis in which she merged Medicare and SEER databases, Dr. Hershman had reported a twofold increased risk of acute myeloid leukemia and myelodysplastic syndrome in elderly women who received a CSF compared with those who did not (J. Natl. Cancer Inst. 2007;99:196-205).

"All that nearly $40 million per year in Medicare expenditures for colony-stimulating factors is buying is toxicity. You’re not buying any disease benefit," argued Dr. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

He proposed that it’s time to consider putting the use of CSFs and dose-dense chemotherapy in elderly patients with hormone receptor–positive tumors on the Quality Oncology Practice Initiative's "do not use" list.

"My thought would be at a minimum we should explain the very small, at-most 8% relative benefit, and the risks. And most people, I think, given the numbers, would say, ‘I’ll take regular chemotherapy, thank you,’ " Dr. Smith predicted.

Dr. Hershman declared having no financial conflicts.

SAN ANTONIO – Curbing colony-stimulating factor use at the start of dose-dense chemotherapy in Medicare patients with hormone receptor–positive breast cancer would save nearly $40 million per year in a population unlikely to gain meaningful benefit from such therapy, according to a new study.

The use of first-cycle colony-stimulating factor (CSF) therapy took off in 2002, Dr. Dawn L. Hershman told attendees at the San Antonio Breast Cancer Symposium. That was the year the benefits of dose-dense chemotherapy were reported, and pegfilgrastim (Neulasta), a granulocyte CSF that was easier to use than those previously available, received marketing approval from the Food and Drug Administration.

A new analysis of Medicare data shows that first-cycle use of CSFs in patients with stage I-III breast cancer jumped from 13% during 1998-2002 to 68% in 2002-2005, reported Dr. Hershman of Columbia University, New York.

In the last half-decade, however, multiple major studies have convincingly shown that the benefits of dose-dense chemotherapy with first-cycle CSFs are confined to breast cancer patients with hormone receptor–negative tumors, according to Dr. Hershman.

For example, one meta-analysis of studies comparing dose-dense to standard chemotherapy in 3,337 estrogen receptor–negative patients showed that dose-dense chemotherapy yielded a 29% reduction in recurrence risk and a 16% improvement in overall survival. In 1,344 estrogen receptor–positive patients, in contrast, dose-dense chemotherapy provided a nonsignificant 8% reduction in recurrence risk and no hint of a benefit in terms of overall survival (J. Natl. Cancer Inst. 2010;102:1845-54).

For the new study, Dr. Hershman and her coauthors identified 10,773 patients in a combined Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were over age 65 with stage I-III breast cancer diagnosed during 1998-2005, and who had at least one chemotherapy claim within 6 months of diagnosis. Of these, 5,266 had a CSF claim during therapy. First-cycle CSF use increased from 13% to 68% over the study period, and the use of pegfilgrastim jumped from 4% to 84%.

"We’re very quick in oncology to adopt, and we never pull back – even when there’s evidence against," Dr. Hershman said. "If we have to make decisions in terms of controlling costs, we shouldn’t be giving drugs that are costly and have no benefit."

Dr. Thomas J. Smith, chair of the session at which Dr. Hershman presented the new study, took the argument further, citing Dr. Hershman’s own earlier study suggesting that CSF therapy in elderly women may actually cause significant harm. In an analysis in which she merged Medicare and SEER databases, Dr. Hershman had reported a twofold increased risk of acute myeloid leukemia and myelodysplastic syndrome in elderly women who received a CSF compared with those who did not (J. Natl. Cancer Inst. 2007;99:196-205).

"All that nearly $40 million per year in Medicare expenditures for colony-stimulating factors is buying is toxicity. You’re not buying any disease benefit," argued Dr. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

He proposed that it’s time to consider putting the use of CSFs and dose-dense chemotherapy in elderly patients with hormone receptor–positive tumors on the Quality Oncology Practice Initiative's "do not use" list.

"My thought would be at a minimum we should explain the very small, at-most 8% relative benefit, and the risks. And most people, I think, given the numbers, would say, ‘I’ll take regular chemotherapy, thank you,’ " Dr. Smith predicted.

Dr. Hershman declared having no financial conflicts.

SAN ANTONIO – Curbing colony-stimulating factor use at the start of dose-dense chemotherapy in Medicare patients with hormone receptor–positive breast cancer would save nearly $40 million per year in a population unlikely to gain meaningful benefit from such therapy, according to a new study.

The use of first-cycle colony-stimulating factor (CSF) therapy took off in 2002, Dr. Dawn L. Hershman told attendees at the San Antonio Breast Cancer Symposium. That was the year the benefits of dose-dense chemotherapy were reported, and pegfilgrastim (Neulasta), a granulocyte CSF that was easier to use than those previously available, received marketing approval from the Food and Drug Administration.

A new analysis of Medicare data shows that first-cycle use of CSFs in patients with stage I-III breast cancer jumped from 13% during 1998-2002 to 68% in 2002-2005, reported Dr. Hershman of Columbia University, New York.

In the last half-decade, however, multiple major studies have convincingly shown that the benefits of dose-dense chemotherapy with first-cycle CSFs are confined to breast cancer patients with hormone receptor–negative tumors, according to Dr. Hershman.

For example, one meta-analysis of studies comparing dose-dense to standard chemotherapy in 3,337 estrogen receptor–negative patients showed that dose-dense chemotherapy yielded a 29% reduction in recurrence risk and a 16% improvement in overall survival. In 1,344 estrogen receptor–positive patients, in contrast, dose-dense chemotherapy provided a nonsignificant 8% reduction in recurrence risk and no hint of a benefit in terms of overall survival (J. Natl. Cancer Inst. 2010;102:1845-54).

For the new study, Dr. Hershman and her coauthors identified 10,773 patients in a combined Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were over age 65 with stage I-III breast cancer diagnosed during 1998-2005, and who had at least one chemotherapy claim within 6 months of diagnosis. Of these, 5,266 had a CSF claim during therapy. First-cycle CSF use increased from 13% to 68% over the study period, and the use of pegfilgrastim jumped from 4% to 84%.

"We’re very quick in oncology to adopt, and we never pull back – even when there’s evidence against," Dr. Hershman said. "If we have to make decisions in terms of controlling costs, we shouldn’t be giving drugs that are costly and have no benefit."

Dr. Thomas J. Smith, chair of the session at which Dr. Hershman presented the new study, took the argument further, citing Dr. Hershman’s own earlier study suggesting that CSF therapy in elderly women may actually cause significant harm. In an analysis in which she merged Medicare and SEER databases, Dr. Hershman had reported a twofold increased risk of acute myeloid leukemia and myelodysplastic syndrome in elderly women who received a CSF compared with those who did not (J. Natl. Cancer Inst. 2007;99:196-205).

"All that nearly $40 million per year in Medicare expenditures for colony-stimulating factors is buying is toxicity. You’re not buying any disease benefit," argued Dr. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

He proposed that it’s time to consider putting the use of CSFs and dose-dense chemotherapy in elderly patients with hormone receptor–positive tumors on the Quality Oncology Practice Initiative's "do not use" list.

"My thought would be at a minimum we should explain the very small, at-most 8% relative benefit, and the risks. And most people, I think, given the numbers, would say, ‘I’ll take regular chemotherapy, thank you,’ " Dr. Smith predicted.

Dr. Hershman declared having no financial conflicts.

ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

ORLANDO – Beta-blockers appear to be cardioprotective in breast cancer patients on trastuzumab, according to a prospective case-control study.

The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B. Cook, Ph.D., reported at the annual scientific sessions of the American Heart Association.

The women on a beta-blocker averaged 59 years of age, a full 8 years older than the breast cancer patients not on a beta-blocker. The patients on a beta-blocker also had significantly higher rates of hypertension, diabetes, obesity, and smoking. After adjustment for these traditional cardiovascular risk factors as well as other factors predisposing to heart failure, including prior treatment with anthracyclines or radiation therapy, the beta-blocker group had an adjusted 83% lower risk of developing cardiotoxicity during 1 year of follow-up on trastuzumab (P = .006).

This is a small hypothesis-generating study. The findings warrant a proper randomized controlled trial assessing the impact of prophylactic beta-blocker therapy in breast cancer patients going on trastuzumab, Dr. Cook asserted.

In all, 22 of the 197 breast cancer patients were on an ACE inhibitor at the time they started on trastuzumab. Logistic regression analysis indicated no cardioprotective effect for this class of medication, according to Dr. Cook of the Cleveland Clinic Foundation.

New-onset heart failure was diagnosed in 11% of patients not on a beta-blocker and in none who were. Left ventricular dysfunction – defined as an echocardiographically documented ejection fraction decline of at least 10% – occurred in 40% of trastuzumab users not on a beta-blocker, compared to 20% who were.

A trajectory analysis of serial echocardiographic exams revealed overall significant declines in left ventricular ejection fraction in patients during their year of follow-up on trastuzumab; however, the decline was markedly steeper in those who were not on a beta-blocker.

Interestingly, neither prior treatment with anthracyclines, even in excess of four cycles, nor other prior chemotherapy were predictive of cardiotoxicity in this series of trastuzumab-treated women. Current smoking, however, was associated with a 4.2-fold increased risk.

Dr. Cook reported no financial conflicts.

Dr. David H. Henry takes you on an audio tour of the December issue of Community Oncology, which includes a discussion and commentary on adding regional nodal irradiation to whole-breast irradiation to improve disease-free survival in breast cancer patient. Other podcast features includes highlights from the San Antonio Breast Cancer Symposium, the International Society of Geriatric Oncology and the Radiological Society of North America.

Dr. David H. Henry takes you on an audio tour of the December issue of Community Oncology, which includes a discussion and commentary on adding regional nodal irradiation to whole-breast irradiation to improve disease-free survival in breast cancer patient. Other podcast features includes highlights from the San Antonio Breast Cancer Symposium, the International Society of Geriatric Oncology and the Radiological Society of North America.

Dr. David H. Henry takes you on an audio tour of the December issue of Community Oncology, which includes a discussion and commentary on adding regional nodal irradiation to whole-breast irradiation to improve disease-free survival in breast cancer patient. Other podcast features includes highlights from the San Antonio Breast Cancer Symposium, the International Society of Geriatric Oncology and the Radiological Society of North America.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.