Bruce Jancin

LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.

During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.

Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.

The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.

This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.

This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.

LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.

During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.

Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.

The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.

This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.

This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.

LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.

During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.

Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.

The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.

This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.

This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.

ORLANDO – Minimally invasive surgical ablation for atrial fibrillation that is refractory to antiarrhythmic agents was significantly more effective than catheter ablation in the first-ever randomized trial comparing the two therapies.

The higher rate of freedom from left atrial arrhythmia that was achieved surgically came at a cost of more procedural complications, most of which were managed conservatively and without prolongation of hospitalization.

The clinical trial was conducted at two European medical centers. It involved 124 patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) who were deemed to be at high risk of having an unsuccessful catheter ablation procedure.

Two-thirds of participants were judged high risk because they had experienced a return of their AF after a prior catheter ablation, whereas the remaining patients were considered at high risk for an unsuccessful catheter ablation because of left atrial enlargement and hypertension, Dr. Lucas V.A. Boersma explained when presenting the results of the FAST (Ablation or Surgery for Atrial Fibrillation Treatment) trial at the annual scientific sessions of the American Heart Association.

Patients were randomized to pulmonary vein isolation by catheter ablation or to a video-assisted thoracoscopic surgical ablation procedure pioneered at the University of Cincinnati (J. Thorac. Cardiovasc. Surg. 2005;130:797-802). Surgical ablation was performed under general anesthesia, but unlike catheter ablation it did not include fluoroscopy, noted Dr. Boersma, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

The primary efficacy end point was freedom from left atrial arrhythmia lasting longer than 30 seconds without antiarrhythmic drugs at 12 months post procedure; this was achieved in 66% of the surgical ablation group, compared with 37% of the catheter ablation group.

Adverse events occurred during the 12 months of follow-up in 34% of the surgical group, compared with 16% of the catheter ablation group. Most of the adverse events in the surgical group were procedural complications, consisting mainly of pneumothorax and bleeding.

Discussant Dr. A. Marc Gillinov, a cardiac surgeon at the Cleveland Clinic, praised FAST as a well-designed, clearly focused study with important clinical implications, given that roughly one-fourth of Americans will eventually develop AF.

"The clear inference from this trial is that if catheter ablation fails and a patient comes to me, I will say to that patient, ‘We have many options, but we now have data to suggest we should discuss surgical ablation as one of those options because if you’ve had a catheter ablation and it failed, surgical ablation has a good chance of restoring you to sinus rhythm," he said.

"Most of the excess morbidity was related to chest drainage: retained fluid or air. I think it’s reasonable to state that those complications are not major and are probably preventable," the surgeon added.

The FAST trial was funded by St. Antonius Hospital and the University of Barcelona Thorax Institute. Dr. Boersma disclosed that he has served as a consultant to Medtronic, and Dr. Gillinov is a consultant to Edwards Lifesciences and AtriCure.

Concurrently with Dr. Boersma’s presentation at the AHA meeting, the FAST results were published in Circulation (doi:10.1161/CIRCULATIONAHA.111.074047).

ORLANDO – Minimally invasive surgical ablation for atrial fibrillation that is refractory to antiarrhythmic agents was significantly more effective than catheter ablation in the first-ever randomized trial comparing the two therapies.

The higher rate of freedom from left atrial arrhythmia that was achieved surgically came at a cost of more procedural complications, most of which were managed conservatively and without prolongation of hospitalization.

The clinical trial was conducted at two European medical centers. It involved 124 patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) who were deemed to be at high risk of having an unsuccessful catheter ablation procedure.

Two-thirds of participants were judged high risk because they had experienced a return of their AF after a prior catheter ablation, whereas the remaining patients were considered at high risk for an unsuccessful catheter ablation because of left atrial enlargement and hypertension, Dr. Lucas V.A. Boersma explained when presenting the results of the FAST (Ablation or Surgery for Atrial Fibrillation Treatment) trial at the annual scientific sessions of the American Heart Association.

Patients were randomized to pulmonary vein isolation by catheter ablation or to a video-assisted thoracoscopic surgical ablation procedure pioneered at the University of Cincinnati (J. Thorac. Cardiovasc. Surg. 2005;130:797-802). Surgical ablation was performed under general anesthesia, but unlike catheter ablation it did not include fluoroscopy, noted Dr. Boersma, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

The primary efficacy end point was freedom from left atrial arrhythmia lasting longer than 30 seconds without antiarrhythmic drugs at 12 months post procedure; this was achieved in 66% of the surgical ablation group, compared with 37% of the catheter ablation group.

Adverse events occurred during the 12 months of follow-up in 34% of the surgical group, compared with 16% of the catheter ablation group. Most of the adverse events in the surgical group were procedural complications, consisting mainly of pneumothorax and bleeding.

Discussant Dr. A. Marc Gillinov, a cardiac surgeon at the Cleveland Clinic, praised FAST as a well-designed, clearly focused study with important clinical implications, given that roughly one-fourth of Americans will eventually develop AF.

"The clear inference from this trial is that if catheter ablation fails and a patient comes to me, I will say to that patient, ‘We have many options, but we now have data to suggest we should discuss surgical ablation as one of those options because if you’ve had a catheter ablation and it failed, surgical ablation has a good chance of restoring you to sinus rhythm," he said.

"Most of the excess morbidity was related to chest drainage: retained fluid or air. I think it’s reasonable to state that those complications are not major and are probably preventable," the surgeon added.

The FAST trial was funded by St. Antonius Hospital and the University of Barcelona Thorax Institute. Dr. Boersma disclosed that he has served as a consultant to Medtronic, and Dr. Gillinov is a consultant to Edwards Lifesciences and AtriCure.

Concurrently with Dr. Boersma’s presentation at the AHA meeting, the FAST results were published in Circulation (doi:10.1161/CIRCULATIONAHA.111.074047).

ORLANDO – Minimally invasive surgical ablation for atrial fibrillation that is refractory to antiarrhythmic agents was significantly more effective than catheter ablation in the first-ever randomized trial comparing the two therapies.

The higher rate of freedom from left atrial arrhythmia that was achieved surgically came at a cost of more procedural complications, most of which were managed conservatively and without prolongation of hospitalization.

The clinical trial was conducted at two European medical centers. It involved 124 patients with drug-refractory paroxysmal or persistent atrial fibrillation (AF) who were deemed to be at high risk of having an unsuccessful catheter ablation procedure.

Two-thirds of participants were judged high risk because they had experienced a return of their AF after a prior catheter ablation, whereas the remaining patients were considered at high risk for an unsuccessful catheter ablation because of left atrial enlargement and hypertension, Dr. Lucas V.A. Boersma explained when presenting the results of the FAST (Ablation or Surgery for Atrial Fibrillation Treatment) trial at the annual scientific sessions of the American Heart Association.

Patients were randomized to pulmonary vein isolation by catheter ablation or to a video-assisted thoracoscopic surgical ablation procedure pioneered at the University of Cincinnati (J. Thorac. Cardiovasc. Surg. 2005;130:797-802). Surgical ablation was performed under general anesthesia, but unlike catheter ablation it did not include fluoroscopy, noted Dr. Boersma, a cardiologist at St. Antonius Hospital, Nieuwegein, the Netherlands.

The primary efficacy end point was freedom from left atrial arrhythmia lasting longer than 30 seconds without antiarrhythmic drugs at 12 months post procedure; this was achieved in 66% of the surgical ablation group, compared with 37% of the catheter ablation group.

Adverse events occurred during the 12 months of follow-up in 34% of the surgical group, compared with 16% of the catheter ablation group. Most of the adverse events in the surgical group were procedural complications, consisting mainly of pneumothorax and bleeding.

Discussant Dr. A. Marc Gillinov, a cardiac surgeon at the Cleveland Clinic, praised FAST as a well-designed, clearly focused study with important clinical implications, given that roughly one-fourth of Americans will eventually develop AF.

"The clear inference from this trial is that if catheter ablation fails and a patient comes to me, I will say to that patient, ‘We have many options, but we now have data to suggest we should discuss surgical ablation as one of those options because if you’ve had a catheter ablation and it failed, surgical ablation has a good chance of restoring you to sinus rhythm," he said.

"Most of the excess morbidity was related to chest drainage: retained fluid or air. I think it’s reasonable to state that those complications are not major and are probably preventable," the surgeon added.

The FAST trial was funded by St. Antonius Hospital and the University of Barcelona Thorax Institute. Dr. Boersma disclosed that he has served as a consultant to Medtronic, and Dr. Gillinov is a consultant to Edwards Lifesciences and AtriCure.

Concurrently with Dr. Boersma’s presentation at the AHA meeting, the FAST results were published in Circulation (doi:10.1161/CIRCULATIONAHA.111.074047).

ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.

Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.

Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.

The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.

Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.

The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.

It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.

She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.

A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).

How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.

"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.

The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).

JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant conflicts of interest.

ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.

Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.

Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.

The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.

Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.

The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.

It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.

She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.

A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).

How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.

"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.

The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).

JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant conflicts of interest.

ORLANDO –The higher a patient’s baseline high-sensitivity C-reactive protein level in the landmark JUPITER study, the greater the incidence of new-onset atrial fibrillation during follow-up, and randomization to rosuvastatin significantly reduced this risk.

Among the 17,120 apparently healthy participants in JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) with no baseline history of atrial fibrillation or other arrhythmia, those in the highest baseline tertile for C-reactive protein (CRP) – that is, more than 5.8 mg/L – had an adjusted 1.96-fold greater incidence of new-onset atrial fibrillation during follow-up, compared with those in the lowest tertile for the inflammatory biomarker, with a CRP of less than 3.2 mg/L, Dr. Jessica M. Peña reported at the annual scientific sessions of the American Heart Association.

Those in the middle tertile had a 1.7-fold increased risk of developing atrial fibrillation after adjustment for age, gender, race, exercise, alcohol intake, current smoking, metabolic syndrome, hypertension, body mass index, and glycosylated hemoglobin.

The incidence of atrial fibrillation was 0.83 cases per 100 person-years in subjects in the top tertile for baseline CRP, 0.75 per 100 person-years for those in the middle tertile, and 0.43 per 100 person-years among patients in the lowest tertile, according to Dr. Peña of Brigham and Women’s Hospital, Boston.

Rosuvastatin (Crestor) proved to have a significant impact upon this risk. The crude incidence was 1.6% with placebo, compared to 1.2% with the statin, which worked out to an adjusted 27% reduction in relative risk in the rosuvastatin group.

The presumed mechanism of benefit lies in the mounting evidence suggesting that inflammation plays a role in both the initiation and maintenance of atrial fibrillation. Statins have anti-inflammatory properties that could be helpful in preventing the arrhythmia, she observed.

It’s important to note that this was a post hoc analysis. Atrial fibrillation was not a prespecified study end point, Dr. Peña stressed. She and her coinvestigators undertook this exploratory analysis because other studies have yielded mixed results regarding statins and atrial fibrillation. The JUPITER analysis provided an opportunity to focus on a population with an underlying proinflammatory state as manifest by the requirement that participants had to have a baseline CRP of at least 2 mg/L.

She and her JUPITER colleagues are now analyzing the data on the relationship between change over time in CRP level and incident atrial fibrillation.

A recently published meta-analysis by University of Oxford (England) researchers looked at published and unpublished data from randomized clinical trials addressing the relationship between statin therapy and atrial fibrillation. The investigators concluded that the available evidence doesn’t support the notion that statins reduce the risk of atrial fibrillation (BMJ 2011 March 16 [doi: 10.1136/bmj.d1250]).

How can this be reconciled with the new JUPITER findings? Dr. Peña surmised that the different study conclusions were probably due to the fact that the various trials involved very different populations and methods of detecting atrial fibrillation.

"Unfortunately, none of these trials, including JUPITER, had atrial fibrillation as a prespecified end point. In the future that will change, but I think until we have better data we can’t definitively answer the question of whether statins protect against atrial fibrillation," Dr. Peña said.

The primary composite end point in JUPITER was myocardial infarction, stroke, cardiovascular death, arterial revascularization, or hospitalization for unstable angina. The rosuvastatin group had a 44% risk reduction compared to controls (N. Engl. J. Med. 2008;359: 2195-207).

JUPITER was funded by AstraZeneca. Dr. Peña reported having no relevant 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.

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 – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

ORLANDO – Patients with atrial fibrillation have an underappreciated high rate of gastrointestinal events, including dyspepsia, GI bleeds, diverticulitis, and gastroesophageal reflux disease.

The rate of symptomatic GI events in patients with atrial fibrillation (AF) rises with increasing CHADS2 score and age. In those AF patients at increased risk for GI events – elderly patients with a higher CHADS2 score – it makes sense for physicians to steer clear whenever possible of the many medications known to increase GI symptoms, Dr. François Laliberté advised at the annual scientific session of the American Heart Association.

He presented an analysis of insurance claims data from the Thomson Reuters MarketScan database for 2005-2009. The study included 413,618 adults diagnosed for the first time with AF and who had no GI events in the 180 days immediately beforehand.

During a mean follow-up of 563 days, the incidence of any diagnosed GI event among these patients – all free of GI symptoms at baseline – was 38.8 events per 100 patient-years, or roughly 39%.

By far the most common GI event was dyspepsia, with an incidence of 14.7 cases per 100 patient-years. This was followed in frequency by diverticula of the intestine at 5.2, gastroesophageal reflux disease at 4.8, and GI bleeding at 4.3 cases per 100 patient-years, reported Dr. Laliberté of the Analysis Group, Montreal.

The rate of GI-related hospitalization was 9.7 per 100 patient-years.

The incidence of GI events was gender-related: 43.6 per 100 patient-years among women with AF and 35.5 in men. The GI event rate steadily rose with age, from 32.2 events per 100 patient-years in patients under age 65 to 52.7 in those age 85 and up.

Patients with a CHADS2 score of 0 had a GI event rate of 30.3 per 100 patient-years. The rate climbed steeply to 41.6 with a CHADS2 score of 1-2, 56.9 with a CHADS2 of 3-4, and 74.5 in patients with a CHADS2 of 5-6.

At baseline, 62% of the AF patients were on one or more medications known to increase the risk of GI events. Leading the list were anticoagulants, used by 19.4% of the study population. Other commonly used medications that promote GI toxicity included opioids, antiplatelet agents, corticosteroids, NSAIDs, selective serotonin receptor inhibitors, bisphosphonates, and calcium channel blockers.

This study was funded by Janssen Scientific Affairs.

ORLANDO – Patients with atrial fibrillation have an underappreciated high rate of gastrointestinal events, including dyspepsia, GI bleeds, diverticulitis, and gastroesophageal reflux disease.

The rate of symptomatic GI events in patients with atrial fibrillation (AF) rises with increasing CHADS2 score and age. In those AF patients at increased risk for GI events – elderly patients with a higher CHADS2 score – it makes sense for physicians to steer clear whenever possible of the many medications known to increase GI symptoms, Dr. François Laliberté advised at the annual scientific session of the American Heart Association.

He presented an analysis of insurance claims data from the Thomson Reuters MarketScan database for 2005-2009. The study included 413,618 adults diagnosed for the first time with AF and who had no GI events in the 180 days immediately beforehand.

During a mean follow-up of 563 days, the incidence of any diagnosed GI event among these patients – all free of GI symptoms at baseline – was 38.8 events per 100 patient-years, or roughly 39%.

By far the most common GI event was dyspepsia, with an incidence of 14.7 cases per 100 patient-years. This was followed in frequency by diverticula of the intestine at 5.2, gastroesophageal reflux disease at 4.8, and GI bleeding at 4.3 cases per 100 patient-years, reported Dr. Laliberté of the Analysis Group, Montreal.

The rate of GI-related hospitalization was 9.7 per 100 patient-years.

The incidence of GI events was gender-related: 43.6 per 100 patient-years among women with AF and 35.5 in men. The GI event rate steadily rose with age, from 32.2 events per 100 patient-years in patients under age 65 to 52.7 in those age 85 and up.

Patients with a CHADS2 score of 0 had a GI event rate of 30.3 per 100 patient-years. The rate climbed steeply to 41.6 with a CHADS2 score of 1-2, 56.9 with a CHADS2 of 3-4, and 74.5 in patients with a CHADS2 of 5-6.

At baseline, 62% of the AF patients were on one or more medications known to increase the risk of GI events. Leading the list were anticoagulants, used by 19.4% of the study population. Other commonly used medications that promote GI toxicity included opioids, antiplatelet agents, corticosteroids, NSAIDs, selective serotonin receptor inhibitors, bisphosphonates, and calcium channel blockers.

This study was funded by Janssen Scientific Affairs.

ORLANDO – Patients with atrial fibrillation have an underappreciated high rate of gastrointestinal events, including dyspepsia, GI bleeds, diverticulitis, and gastroesophageal reflux disease.

The rate of symptomatic GI events in patients with atrial fibrillation (AF) rises with increasing CHADS2 score and age. In those AF patients at increased risk for GI events – elderly patients with a higher CHADS2 score – it makes sense for physicians to steer clear whenever possible of the many medications known to increase GI symptoms, Dr. François Laliberté advised at the annual scientific session of the American Heart Association.

He presented an analysis of insurance claims data from the Thomson Reuters MarketScan database for 2005-2009. The study included 413,618 adults diagnosed for the first time with AF and who had no GI events in the 180 days immediately beforehand.

During a mean follow-up of 563 days, the incidence of any diagnosed GI event among these patients – all free of GI symptoms at baseline – was 38.8 events per 100 patient-years, or roughly 39%.

By far the most common GI event was dyspepsia, with an incidence of 14.7 cases per 100 patient-years. This was followed in frequency by diverticula of the intestine at 5.2, gastroesophageal reflux disease at 4.8, and GI bleeding at 4.3 cases per 100 patient-years, reported Dr. Laliberté of the Analysis Group, Montreal.

The rate of GI-related hospitalization was 9.7 per 100 patient-years.

The incidence of GI events was gender-related: 43.6 per 100 patient-years among women with AF and 35.5 in men. The GI event rate steadily rose with age, from 32.2 events per 100 patient-years in patients under age 65 to 52.7 in those age 85 and up.

Patients with a CHADS2 score of 0 had a GI event rate of 30.3 per 100 patient-years. The rate climbed steeply to 41.6 with a CHADS2 score of 1-2, 56.9 with a CHADS2 of 3-4, and 74.5 in patients with a CHADS2 of 5-6.

At baseline, 62% of the AF patients were on one or more medications known to increase the risk of GI events. Leading the list were anticoagulants, used by 19.4% of the study population. Other commonly used medications that promote GI toxicity included opioids, antiplatelet agents, corticosteroids, NSAIDs, selective serotonin receptor inhibitors, bisphosphonates, and calcium channel blockers.

This study was funded by Janssen Scientific Affairs.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Diagnosis of diabetes within the prior 4 years was independently associated with breast cancer in a Swedish case-control study.

Dr. Håkan Olsson reported at the San Antonio Breast Cancer Symposium on all 2,724 women diagnosed with breast cancer in southern Sweden during 2005-2007 and 20,542 matched controls. He and his coworkers were interested in how the malignancy is related to diabetes, obesity, and serum lipid levels.

In a multivariate analysis adjusted for obesity, serum lipids, and other potential confounders, the breast cancer patients were 37% more likely than controls to have been diagnosed with diabetes during the previous 4 years. Yet diabetes diagnosed 4-10 years previously was not associated with a significant increase in breast cancer, said Dr. Olsson, professor of oncology and cancer epidemiology at Lund (Sweden) University.

The most likely explanation for the finding that only relatively recently diagnosed diabetes was linked to increased risk of breast cancer is that the diabetic hormonal milieu doesn’t initiate breast tumors, but rather it promotes the growth of tumors that are already established but dormant. This would be analogous to the relationship between hormone replacement therapy and breast cancer, where the Early Breast Cancer Trialists’ Collaborative Group has demonstrated that it’s only present use, not past use, that increases the risk of malignancy, he observed.

Dr. Olsson and coworkers also looked at the relationship between diabetes and all other types of cancer among patients in the comprehensive regional cancer registry. They found that three other types of cancer in addition to breast cancer were associated with a significantly increased likelihood of prior diagnosis of diabetes compared to controls: pancreatic cancer, with a 2.36-fold increased rate; liver cancer, with a 3.43-fold increased odds; and colon cancer, with a 1.49-fold increase.

Dr. Olsson and coworkers also looked at the relationship between the antidiabetic medications metformin and glargine and cancer risk among all patients in the cancer registry, not just those with breast cancer. Use of the long-acting insulin analog glargine, which is quite common among Swedish type 2 diabetic patients, was associated with a 2.88-fold increased overall cancer risk. In contrast, metformin use was associated with an 8% reduction in overall cancer risk, although this association didn’t achieve statistical significance, unlike the relationship between glargine and overall cancer.

An association between glargine and increased cancer risk has also been noted in several other studies, according to Dr. Olsson.

In the southern Swedish breast cancer cohort, obesity after age 60 was independently associated with a 55% increased likelihood of breast cancer after controlling for diabetes and other factors in a multivariate analysis. However, obesity in women under age 60 was associated with a nonsignificant 41% reduction in breast cancer.

To Dr. Olsson’s surprise, the investigators found that hypercholesterolemia was independently associated with a 27% reduction in the prevalence of breast cancer. In other words, significantly fewer breast cancer patients had a high cholesterol level compared with the general population. This is a novel finding that requires confirmation in other data sets, he added.

The relationship between metformin and breast cancer is under study in the large, prospective, phase III, double-blind, randomized MA 32 clinical trial led by the National Cancer Institute of Canada Clinical Trials Group. More than 1,000 nondiabetic patients with early-stage breast cancer have been randomized to metformin or placebo. Key end points in the MA 32 study include overall and disease-free survival. Results are about 5 years off.

Dr. Olsson’s study was funded by the Southern Sweden Health Care Region. He declared having no relevant financial relationships.

SAN ANTONIO – Diagnosis of diabetes within the prior 4 years was independently associated with breast cancer in a Swedish case-control study.

Dr. Håkan Olsson reported at the San Antonio Breast Cancer Symposium on all 2,724 women diagnosed with breast cancer in southern Sweden during 2005-2007 and 20,542 matched controls. He and his coworkers were interested in how the malignancy is related to diabetes, obesity, and serum lipid levels.

In a multivariate analysis adjusted for obesity, serum lipids, and other potential confounders, the breast cancer patients were 37% more likely than controls to have been diagnosed with diabetes during the previous 4 years. Yet diabetes diagnosed 4-10 years previously was not associated with a significant increase in breast cancer, said Dr. Olsson, professor of oncology and cancer epidemiology at Lund (Sweden) University.

The most likely explanation for the finding that only relatively recently diagnosed diabetes was linked to increased risk of breast cancer is that the diabetic hormonal milieu doesn’t initiate breast tumors, but rather it promotes the growth of tumors that are already established but dormant. This would be analogous to the relationship between hormone replacement therapy and breast cancer, where the Early Breast Cancer Trialists’ Collaborative Group has demonstrated that it’s only present use, not past use, that increases the risk of malignancy, he observed.

Dr. Olsson and coworkers also looked at the relationship between diabetes and all other types of cancer among patients in the comprehensive regional cancer registry. They found that three other types of cancer in addition to breast cancer were associated with a significantly increased likelihood of prior diagnosis of diabetes compared to controls: pancreatic cancer, with a 2.36-fold increased rate; liver cancer, with a 3.43-fold increased odds; and colon cancer, with a 1.49-fold increase.

Dr. Olsson and coworkers also looked at the relationship between the antidiabetic medications metformin and glargine and cancer risk among all patients in the cancer registry, not just those with breast cancer. Use of the long-acting insulin analog glargine, which is quite common among Swedish type 2 diabetic patients, was associated with a 2.88-fold increased overall cancer risk. In contrast, metformin use was associated with an 8% reduction in overall cancer risk, although this association didn’t achieve statistical significance, unlike the relationship between glargine and overall cancer.

An association between glargine and increased cancer risk has also been noted in several other studies, according to Dr. Olsson.

In the southern Swedish breast cancer cohort, obesity after age 60 was independently associated with a 55% increased likelihood of breast cancer after controlling for diabetes and other factors in a multivariate analysis. However, obesity in women under age 60 was associated with a nonsignificant 41% reduction in breast cancer.

To Dr. Olsson’s surprise, the investigators found that hypercholesterolemia was independently associated with a 27% reduction in the prevalence of breast cancer. In other words, significantly fewer breast cancer patients had a high cholesterol level compared with the general population. This is a novel finding that requires confirmation in other data sets, he added.

The relationship between metformin and breast cancer is under study in the large, prospective, phase III, double-blind, randomized MA 32 clinical trial led by the National Cancer Institute of Canada Clinical Trials Group. More than 1,000 nondiabetic patients with early-stage breast cancer have been randomized to metformin or placebo. Key end points in the MA 32 study include overall and disease-free survival. Results are about 5 years off.

Dr. Olsson’s study was funded by the Southern Sweden Health Care Region. He declared having no relevant financial relationships.

SAN ANTONIO – Diagnosis of diabetes within the prior 4 years was independently associated with breast cancer in a Swedish case-control study.

Dr. Håkan Olsson reported at the San Antonio Breast Cancer Symposium on all 2,724 women diagnosed with breast cancer in southern Sweden during 2005-2007 and 20,542 matched controls. He and his coworkers were interested in how the malignancy is related to diabetes, obesity, and serum lipid levels.

In a multivariate analysis adjusted for obesity, serum lipids, and other potential confounders, the breast cancer patients were 37% more likely than controls to have been diagnosed with diabetes during the previous 4 years. Yet diabetes diagnosed 4-10 years previously was not associated with a significant increase in breast cancer, said Dr. Olsson, professor of oncology and cancer epidemiology at Lund (Sweden) University.

The most likely explanation for the finding that only relatively recently diagnosed diabetes was linked to increased risk of breast cancer is that the diabetic hormonal milieu doesn’t initiate breast tumors, but rather it promotes the growth of tumors that are already established but dormant. This would be analogous to the relationship between hormone replacement therapy and breast cancer, where the Early Breast Cancer Trialists’ Collaborative Group has demonstrated that it’s only present use, not past use, that increases the risk of malignancy, he observed.

Dr. Olsson and coworkers also looked at the relationship between diabetes and all other types of cancer among patients in the comprehensive regional cancer registry. They found that three other types of cancer in addition to breast cancer were associated with a significantly increased likelihood of prior diagnosis of diabetes compared to controls: pancreatic cancer, with a 2.36-fold increased rate; liver cancer, with a 3.43-fold increased odds; and colon cancer, with a 1.49-fold increase.

Dr. Olsson and coworkers also looked at the relationship between the antidiabetic medications metformin and glargine and cancer risk among all patients in the cancer registry, not just those with breast cancer. Use of the long-acting insulin analog glargine, which is quite common among Swedish type 2 diabetic patients, was associated with a 2.88-fold increased overall cancer risk. In contrast, metformin use was associated with an 8% reduction in overall cancer risk, although this association didn’t achieve statistical significance, unlike the relationship between glargine and overall cancer.

An association between glargine and increased cancer risk has also been noted in several other studies, according to Dr. Olsson.

In the southern Swedish breast cancer cohort, obesity after age 60 was independently associated with a 55% increased likelihood of breast cancer after controlling for diabetes and other factors in a multivariate analysis. However, obesity in women under age 60 was associated with a nonsignificant 41% reduction in breast cancer.

To Dr. Olsson’s surprise, the investigators found that hypercholesterolemia was independently associated with a 27% reduction in the prevalence of breast cancer. In other words, significantly fewer breast cancer patients had a high cholesterol level compared with the general population. This is a novel finding that requires confirmation in other data sets, he added.

The relationship between metformin and breast cancer is under study in the large, prospective, phase III, double-blind, randomized MA 32 clinical trial led by the National Cancer Institute of Canada Clinical Trials Group. More than 1,000 nondiabetic patients with early-stage breast cancer have been randomized to metformin or placebo. Key end points in the MA 32 study include overall and disease-free survival. Results are about 5 years off.

Dr. Olsson’s study was funded by the Southern Sweden Health Care Region. He declared having no relevant financial relationships.

SAN ANTONIO – Pregnancy-associated breast cancer carries a relatively poor prognosis regardless of whether the malignancy is diagnosed during pregnancy or post partum, a meta-analysis has shown.

The meta-analysis included 29 matched case-control studies totaling 3,529 women with pregnancy-associated breast cancer – defined as breast cancer diagnosed during pregnancy or within 1 year afterward – and 36,914 controls whose breast cancer was unrelated to pregnancy.

This is believed to be the largest-ever meta-analysis addressing the prognosis of pregnancy-associated breast cancer, a relatively rare disease, Dr. Hatem A. Azim Jr. reported at the annual San Antonio Breast Cancer Symposium. In addition to the published reports, Dr. Azim and coauthors contacted the various study investigators to obtain unpublished data.

Women with pregnancy-associated breast cancer had a significantly greater risk of death than did controls, Dr. Azim and colleagues found: In a multivariate analysis, pregnancy increased the overall mortality rate by 46%. This held true even after adjustment for differences in tumor size, nodal status, and systemic therapy, according to Dr. Azim of the Jules Bordet Institute at the Free University of Brussels.

The secondary outcome measure in the meta-analysis was disease-free survival. Patients with pregnancy-associated breast cancer had a 59% increased risk of relapse compared with women with nonpregnancy-related breast cancer.

Roughly 6% of breast cancers are diagnosed in women before the age of 40, and of those only about 10% are diagnosed during pregnancy or within a year after. The relative rarity of this condition precludes conducting definitive large prospective clinical trials addressing patient prognosis.

Despite the rarity of pregnancy-associated breast cancer, however, it’s an important condition for a couple of reasons: The incidence of pregnancy-associated breast cancer is increasing because of the popular trend for delay of childbirth until later in life, and the condition poses a thorny therapeutic challenge because of the poor prognosis.

Dr. Azim reported no relevant financial disclosures.

SAN ANTONIO – Pregnancy-associated breast cancer carries a relatively poor prognosis regardless of whether the malignancy is diagnosed during pregnancy or post partum, a meta-analysis has shown.

The meta-analysis included 29 matched case-control studies totaling 3,529 women with pregnancy-associated breast cancer – defined as breast cancer diagnosed during pregnancy or within 1 year afterward – and 36,914 controls whose breast cancer was unrelated to pregnancy.

This is believed to be the largest-ever meta-analysis addressing the prognosis of pregnancy-associated breast cancer, a relatively rare disease, Dr. Hatem A. Azim Jr. reported at the annual San Antonio Breast Cancer Symposium. In addition to the published reports, Dr. Azim and coauthors contacted the various study investigators to obtain unpublished data.

Women with pregnancy-associated breast cancer had a significantly greater risk of death than did controls, Dr. Azim and colleagues found: In a multivariate analysis, pregnancy increased the overall mortality rate by 46%. This held true even after adjustment for differences in tumor size, nodal status, and systemic therapy, according to Dr. Azim of the Jules Bordet Institute at the Free University of Brussels.

The secondary outcome measure in the meta-analysis was disease-free survival. Patients with pregnancy-associated breast cancer had a 59% increased risk of relapse compared with women with nonpregnancy-related breast cancer.

Roughly 6% of breast cancers are diagnosed in women before the age of 40, and of those only about 10% are diagnosed during pregnancy or within a year after. The relative rarity of this condition precludes conducting definitive large prospective clinical trials addressing patient prognosis.

Despite the rarity of pregnancy-associated breast cancer, however, it’s an important condition for a couple of reasons: The incidence of pregnancy-associated breast cancer is increasing because of the popular trend for delay of childbirth until later in life, and the condition poses a thorny therapeutic challenge because of the poor prognosis.

Dr. Azim reported no relevant financial disclosures.

SAN ANTONIO – Pregnancy-associated breast cancer carries a relatively poor prognosis regardless of whether the malignancy is diagnosed during pregnancy or post partum, a meta-analysis has shown.

The meta-analysis included 29 matched case-control studies totaling 3,529 women with pregnancy-associated breast cancer – defined as breast cancer diagnosed during pregnancy or within 1 year afterward – and 36,914 controls whose breast cancer was unrelated to pregnancy.

This is believed to be the largest-ever meta-analysis addressing the prognosis of pregnancy-associated breast cancer, a relatively rare disease, Dr. Hatem A. Azim Jr. reported at the annual San Antonio Breast Cancer Symposium. In addition to the published reports, Dr. Azim and coauthors contacted the various study investigators to obtain unpublished data.

Women with pregnancy-associated breast cancer had a significantly greater risk of death than did controls, Dr. Azim and colleagues found: In a multivariate analysis, pregnancy increased the overall mortality rate by 46%. This held true even after adjustment for differences in tumor size, nodal status, and systemic therapy, according to Dr. Azim of the Jules Bordet Institute at the Free University of Brussels.

The secondary outcome measure in the meta-analysis was disease-free survival. Patients with pregnancy-associated breast cancer had a 59% increased risk of relapse compared with women with nonpregnancy-related breast cancer.

Roughly 6% of breast cancers are diagnosed in women before the age of 40, and of those only about 10% are diagnosed during pregnancy or within a year after. The relative rarity of this condition precludes conducting definitive large prospective clinical trials addressing patient prognosis.

Despite the rarity of pregnancy-associated breast cancer, however, it’s an important condition for a couple of reasons: The incidence of pregnancy-associated breast cancer is increasing because of the popular trend for delay of childbirth until later in life, and the condition poses a thorny therapeutic challenge because of the poor prognosis.

Dr. Azim reported no relevant financial disclosures.