Michele G. Sullivan

SAN ANTONIO – Women who received paclitaxel and trastuzumab after anthracycline chemotherapy for HER2-positive breast cancer were almost 40% less likely to die by 10 years than were those given only paclitaxel in a pair of landmark clinical trials.

"This means that 80% of these patients – most of whom had node-positive disease – were alive at 10 years after their diagnosis of breast cancer." said Dr. Edward H. Romond, reporting long-term findings at the annual San Antonio Breast Cancer Symposium.

The regimen also reduced the risk of a 10-year disease-free survival event by 40% in the definitive survival analysis of the two pivotal trastuzumab (Herceptin) studies – the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 protocol and the North Central Cancer Treatment Group (NCCTG) N9831 trial.

Both studies compared the paclitaxel/trastuzumab combination with paclitaxel alone in women with invasive HER2-positive breast cancers. All patients had undergone a lumpectomy or mastectomy with pathologically clear margins, and had axillary nodes that were initially pathologically involved.

Outcomes of both trials have been separately reported. However, because of their similar structure, treatment regimens, and patient populations, the Food and Drug Administration agreed to combine them to allow for a definite survival analysis, said Dr. Romond of the University of Kentucky, Lexington.

The combined analysis comprised 4,046 patients, 2,028 of whom took the paclitaxel/trastuzumab combination and 2,018 of whom took paclitaxel alone. The median follow-up in the combined analysis was 8.4 years, with data available for up to 10 years.

About half of the patients were younger than 50 years. Most had node positive disease; slightly more than half had hormone receptor positive–breast cancer. The tumor was T1 in 40%, T2 in 50%, and T3 in 10%.

By the end of the follow-up period, 680 disease-free survival events had occurred in the paclitaxel-only group vs. 473 in the combination therapy group (hazard ratio, 0.60; P less than .0001).

The disease-free survival curve began to separate shortly before year 2. The difference became significant around year 5; by year 6, 81% of the combination group and 69% of the single-therapy group were without an event. By year 10, the rates of disease-free survival were 74% and 62% - an absolute difference of 11.5%.

Most events in each group were distant recurrences (227 with the combination and 391 with single-therapy). Local or regional recurrence was seen in 84 and 124, respectively, and contralateral breast disease in 46 and 40. About 4% of women in each group developed a second primary cancer, and about 2% in each group died without a recurrence of their breast cancer.

There were 286 deaths in the combination group and 418 in the paclitaxel-only group. Women in the combination-therapy group were 37% less likely to die than were those who took paclitaxel alone – a significant difference (HR, 0.63; P less than .0001)

The survival curves began to diverge around year 2 and continued to separate throughout the follow-up period. By year 10, 84% of those in the combination group and 75% of those in the single therapy group were still alive, an absolute difference of 9%.

The survival advantage was apparent whether women had hormone receptor positive or negative disease, Dr. Romond noted (HR, 0.61 and 0.64, respectively).

Most deaths in both groups were due to the original breast cancer (209 in the combination group and 340 in the paclitaxel-only group). Other causes of death were a second primary cancer (25 and 41, respectively), or other or unknown causes.

The combination treatment was especially helpful for women with high risk factors, conferring a significant survival advantage over paclitaxel alone to women aged 60 years and older (14%), women with 10 more positive nodes (16%), and women with tumors larger than 5 cm (12%).

Dr. Romond had no financial disclosures.

SAN ANTONIO – Women who received paclitaxel and trastuzumab after anthracycline chemotherapy for HER2-positive breast cancer were almost 40% less likely to die by 10 years than were those given only paclitaxel in a pair of landmark clinical trials.

"This means that 80% of these patients – most of whom had node-positive disease – were alive at 10 years after their diagnosis of breast cancer." said Dr. Edward H. Romond, reporting long-term findings at the annual San Antonio Breast Cancer Symposium.

The regimen also reduced the risk of a 10-year disease-free survival event by 40% in the definitive survival analysis of the two pivotal trastuzumab (Herceptin) studies – the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 protocol and the North Central Cancer Treatment Group (NCCTG) N9831 trial.

Both studies compared the paclitaxel/trastuzumab combination with paclitaxel alone in women with invasive HER2-positive breast cancers. All patients had undergone a lumpectomy or mastectomy with pathologically clear margins, and had axillary nodes that were initially pathologically involved.

Outcomes of both trials have been separately reported. However, because of their similar structure, treatment regimens, and patient populations, the Food and Drug Administration agreed to combine them to allow for a definite survival analysis, said Dr. Romond of the University of Kentucky, Lexington.

The combined analysis comprised 4,046 patients, 2,028 of whom took the paclitaxel/trastuzumab combination and 2,018 of whom took paclitaxel alone. The median follow-up in the combined analysis was 8.4 years, with data available for up to 10 years.

About half of the patients were younger than 50 years. Most had node positive disease; slightly more than half had hormone receptor positive–breast cancer. The tumor was T1 in 40%, T2 in 50%, and T3 in 10%.

By the end of the follow-up period, 680 disease-free survival events had occurred in the paclitaxel-only group vs. 473 in the combination therapy group (hazard ratio, 0.60; P less than .0001).

The disease-free survival curve began to separate shortly before year 2. The difference became significant around year 5; by year 6, 81% of the combination group and 69% of the single-therapy group were without an event. By year 10, the rates of disease-free survival were 74% and 62% - an absolute difference of 11.5%.

Most events in each group were distant recurrences (227 with the combination and 391 with single-therapy). Local or regional recurrence was seen in 84 and 124, respectively, and contralateral breast disease in 46 and 40. About 4% of women in each group developed a second primary cancer, and about 2% in each group died without a recurrence of their breast cancer.

There were 286 deaths in the combination group and 418 in the paclitaxel-only group. Women in the combination-therapy group were 37% less likely to die than were those who took paclitaxel alone – a significant difference (HR, 0.63; P less than .0001)

The survival curves began to diverge around year 2 and continued to separate throughout the follow-up period. By year 10, 84% of those in the combination group and 75% of those in the single therapy group were still alive, an absolute difference of 9%.

The survival advantage was apparent whether women had hormone receptor positive or negative disease, Dr. Romond noted (HR, 0.61 and 0.64, respectively).

Most deaths in both groups were due to the original breast cancer (209 in the combination group and 340 in the paclitaxel-only group). Other causes of death were a second primary cancer (25 and 41, respectively), or other or unknown causes.

The combination treatment was especially helpful for women with high risk factors, conferring a significant survival advantage over paclitaxel alone to women aged 60 years and older (14%), women with 10 more positive nodes (16%), and women with tumors larger than 5 cm (12%).

Dr. Romond had no financial disclosures.

SAN ANTONIO – Women who received paclitaxel and trastuzumab after anthracycline chemotherapy for HER2-positive breast cancer were almost 40% less likely to die by 10 years than were those given only paclitaxel in a pair of landmark clinical trials.

"This means that 80% of these patients – most of whom had node-positive disease – were alive at 10 years after their diagnosis of breast cancer." said Dr. Edward H. Romond, reporting long-term findings at the annual San Antonio Breast Cancer Symposium.

The regimen also reduced the risk of a 10-year disease-free survival event by 40% in the definitive survival analysis of the two pivotal trastuzumab (Herceptin) studies – the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 protocol and the North Central Cancer Treatment Group (NCCTG) N9831 trial.

Both studies compared the paclitaxel/trastuzumab combination with paclitaxel alone in women with invasive HER2-positive breast cancers. All patients had undergone a lumpectomy or mastectomy with pathologically clear margins, and had axillary nodes that were initially pathologically involved.

Outcomes of both trials have been separately reported. However, because of their similar structure, treatment regimens, and patient populations, the Food and Drug Administration agreed to combine them to allow for a definite survival analysis, said Dr. Romond of the University of Kentucky, Lexington.

The combined analysis comprised 4,046 patients, 2,028 of whom took the paclitaxel/trastuzumab combination and 2,018 of whom took paclitaxel alone. The median follow-up in the combined analysis was 8.4 years, with data available for up to 10 years.

About half of the patients were younger than 50 years. Most had node positive disease; slightly more than half had hormone receptor positive–breast cancer. The tumor was T1 in 40%, T2 in 50%, and T3 in 10%.

By the end of the follow-up period, 680 disease-free survival events had occurred in the paclitaxel-only group vs. 473 in the combination therapy group (hazard ratio, 0.60; P less than .0001).

The disease-free survival curve began to separate shortly before year 2. The difference became significant around year 5; by year 6, 81% of the combination group and 69% of the single-therapy group were without an event. By year 10, the rates of disease-free survival were 74% and 62% - an absolute difference of 11.5%.

Most events in each group were distant recurrences (227 with the combination and 391 with single-therapy). Local or regional recurrence was seen in 84 and 124, respectively, and contralateral breast disease in 46 and 40. About 4% of women in each group developed a second primary cancer, and about 2% in each group died without a recurrence of their breast cancer.

There were 286 deaths in the combination group and 418 in the paclitaxel-only group. Women in the combination-therapy group were 37% less likely to die than were those who took paclitaxel alone – a significant difference (HR, 0.63; P less than .0001)

The survival curves began to diverge around year 2 and continued to separate throughout the follow-up period. By year 10, 84% of those in the combination group and 75% of those in the single therapy group were still alive, an absolute difference of 9%.

The survival advantage was apparent whether women had hormone receptor positive or negative disease, Dr. Romond noted (HR, 0.61 and 0.64, respectively).

Most deaths in both groups were due to the original breast cancer (209 in the combination group and 340 in the paclitaxel-only group). Other causes of death were a second primary cancer (25 and 41, respectively), or other or unknown causes.

The combination treatment was especially helpful for women with high risk factors, conferring a significant survival advantage over paclitaxel alone to women aged 60 years and older (14%), women with 10 more positive nodes (16%), and women with tumors larger than 5 cm (12%).

Dr. Romond had no financial disclosures.

Colorectal surgical site infections dropped by an average of 32% among hospitals that participated in a project designed to reduce facility-specific infection risk factors.

The project – co-sponsored by the Joint Commission Center for Transforming Healthcare and the American College of Surgeons – will result in a user-friendly online tool that can examine any hospital’s infections data and recommend detailed, site-specific interventions.

The commission’s Targeted Solutions Tool should be available by the middle of 2013.

"The hospitals we engaged have mastered these sophisticated change tools, and now we need to make sure this learning can be spread to others," Dr. Mark Chassin said during a press briefing. "[The new tool] will be a very easy-to-follow approach that applies all the lessons we learned – showing how to measure infection rates, figure out which contributing factors are present in their institution, and guiding them through implementations proven to address these factors."

The commission chose to tackle colorectal surgical site infections (SSIs) because they are common, dangerous, and expensive, said Dr. Chassin, president of the group. Unfortunately, risk factors don’t respond to a "one size fits all" prevention protocol. "These factors are highly variable across hospitals, suggesting that there are opportunities to improve performance."

The 2-year pilot project included seven hospitals of varying size and community demographics. The facilities tracked their colorectal SSI patterns using the American College of Surgeons National Surgical Quality Improvement Program. Each hospital then developed interventions targeted at their individual modifiable risk factors, implemented the changes, and recorded their results.

Overall, the protocol reduced colorectal SSIs by 32% – from an average of 16% to 11%. Superficial skin SSIs fell by an average of 45% over the entire study group.

The protocol improved other outcomes as well, Dr. Chassin said. The average length of stay for a colorectal surgery patient with a wound infection decreased from 15 to 13 days. Across the group, the changes were associated with a savings of almost $4 million.

The hospitals collectively identified 34 factors that greatly increased the risk of such infections. During the briefing, Dr. Jenna Lovely, the surgical pharmacotherapy manager at the Mayo Clinic, Rochester, Minn., shared some of their results (J. Am. Coll. Surg. 2011;213:83-92; 2012 [doi:10.1016/j.jamcollsurg.2012.09.009]).

Before implementation of the program, the colorectal SSI rate at Mayo was 10%. With a goal of reducing that number by at least 50%, the team examined risk factors in the preoperative, intraoperative, postoperative, and posthospitalization periods and made some changes, Dr. Lovely said.

Preoperatively, every patient now takes a shower with soap or with a chlorhexidine-based cleanser both the night before and the day of surgery.

Intraoperatively, the site is prepped with an antimicrobial cleansing agent, and the correct antibiotic is administered at 1 hour before the incision is made. If the surgery lasts more than 4 hours, a second dose of the same antibiotic is administered; cefazolin is given 24 hours after closing.

At fascia closing, the surgeon dons a complete change of gown, mask, and gloves. Closing is performed with the use of an entirely new set of instruments.

Postoperatively, everyone who comes in contact with the wound – including staff, the patient, and visitors – practices good hand hygiene. Reminder notes and hand cleanser are located prominently in rooms and all around the unit. Nurses are empowered to change dressings as needed. Wound probing occurs as needed to help expel any contaminated fluids.

Patients are discharged with infection control education and a bottle of chlorhexidine cleanser.

"These changes are embedded in the environment across the continuum of care. It’s part of the surgical unit’s culture, and this makes it easier to do the right thing. The changes also allow the surgeon to focus on doing what he does best – providing a timely and efficient surgery with the best possible outcome," Dr. Lovely said.

Implementation of these changes led to a reduction in SSI rate from 10% to 4%, and that rate has maintained this rate for 18 months.

Dr. Shirin Towfigh, a surgeon at Cedars-Sinai Medical Center in Los Angeles, said her unit experienced a similar improvement.

The project included 46 surgeons and all of the unit staff. Because the team didn’t want to dictate surgical technique, she said, their goal "was to come up with processes that would improve results independent of a surgeon’s practice. We wanted the changes to be effective, but also easy for surgeons to implement in their own practice."

By the end of the study period, the unit’s colorectal SSI rate had decreased by 50%. Since the project closed 6 months ago, that has further improved, with a total decrease of 65%.

"This is a problem colorectal surgeons have been struggling with for years," Dr. Chassin said. "We’ve always tried to get at it with the simple answer: ‘Here are 5 or 10 things everyone should do to decrease SSIs.’ That doesn’t work, because the critical factors that explain poor outcomes differ from one place to another. The best advice I can give is to look at all your contributing factors and assess where your organization falls short. Use these findings as a guide for where to focus your improvement efforts. The only way you know how to improve is to measure the cause of problems and target interventions right to them."

No disclosures were reported.

Colorectal surgical site infections dropped by an average of 32% among hospitals that participated in a project designed to reduce facility-specific infection risk factors.

The project – co-sponsored by the Joint Commission Center for Transforming Healthcare and the American College of Surgeons – will result in a user-friendly online tool that can examine any hospital’s infections data and recommend detailed, site-specific interventions.

The commission’s Targeted Solutions Tool should be available by the middle of 2013.

"The hospitals we engaged have mastered these sophisticated change tools, and now we need to make sure this learning can be spread to others," Dr. Mark Chassin said during a press briefing. "[The new tool] will be a very easy-to-follow approach that applies all the lessons we learned – showing how to measure infection rates, figure out which contributing factors are present in their institution, and guiding them through implementations proven to address these factors."

The commission chose to tackle colorectal surgical site infections (SSIs) because they are common, dangerous, and expensive, said Dr. Chassin, president of the group. Unfortunately, risk factors don’t respond to a "one size fits all" prevention protocol. "These factors are highly variable across hospitals, suggesting that there are opportunities to improve performance."

The 2-year pilot project included seven hospitals of varying size and community demographics. The facilities tracked their colorectal SSI patterns using the American College of Surgeons National Surgical Quality Improvement Program. Each hospital then developed interventions targeted at their individual modifiable risk factors, implemented the changes, and recorded their results.

Overall, the protocol reduced colorectal SSIs by 32% – from an average of 16% to 11%. Superficial skin SSIs fell by an average of 45% over the entire study group.

The protocol improved other outcomes as well, Dr. Chassin said. The average length of stay for a colorectal surgery patient with a wound infection decreased from 15 to 13 days. Across the group, the changes were associated with a savings of almost $4 million.

The hospitals collectively identified 34 factors that greatly increased the risk of such infections. During the briefing, Dr. Jenna Lovely, the surgical pharmacotherapy manager at the Mayo Clinic, Rochester, Minn., shared some of their results (J. Am. Coll. Surg. 2011;213:83-92; 2012 [doi:10.1016/j.jamcollsurg.2012.09.009]).

Before implementation of the program, the colorectal SSI rate at Mayo was 10%. With a goal of reducing that number by at least 50%, the team examined risk factors in the preoperative, intraoperative, postoperative, and posthospitalization periods and made some changes, Dr. Lovely said.

Preoperatively, every patient now takes a shower with soap or with a chlorhexidine-based cleanser both the night before and the day of surgery.

Intraoperatively, the site is prepped with an antimicrobial cleansing agent, and the correct antibiotic is administered at 1 hour before the incision is made. If the surgery lasts more than 4 hours, a second dose of the same antibiotic is administered; cefazolin is given 24 hours after closing.

At fascia closing, the surgeon dons a complete change of gown, mask, and gloves. Closing is performed with the use of an entirely new set of instruments.

Postoperatively, everyone who comes in contact with the wound – including staff, the patient, and visitors – practices good hand hygiene. Reminder notes and hand cleanser are located prominently in rooms and all around the unit. Nurses are empowered to change dressings as needed. Wound probing occurs as needed to help expel any contaminated fluids.

Patients are discharged with infection control education and a bottle of chlorhexidine cleanser.

"These changes are embedded in the environment across the continuum of care. It’s part of the surgical unit’s culture, and this makes it easier to do the right thing. The changes also allow the surgeon to focus on doing what he does best – providing a timely and efficient surgery with the best possible outcome," Dr. Lovely said.

Implementation of these changes led to a reduction in SSI rate from 10% to 4%, and that rate has maintained this rate for 18 months.

Dr. Shirin Towfigh, a surgeon at Cedars-Sinai Medical Center in Los Angeles, said her unit experienced a similar improvement.

The project included 46 surgeons and all of the unit staff. Because the team didn’t want to dictate surgical technique, she said, their goal "was to come up with processes that would improve results independent of a surgeon’s practice. We wanted the changes to be effective, but also easy for surgeons to implement in their own practice."

By the end of the study period, the unit’s colorectal SSI rate had decreased by 50%. Since the project closed 6 months ago, that has further improved, with a total decrease of 65%.

"This is a problem colorectal surgeons have been struggling with for years," Dr. Chassin said. "We’ve always tried to get at it with the simple answer: ‘Here are 5 or 10 things everyone should do to decrease SSIs.’ That doesn’t work, because the critical factors that explain poor outcomes differ from one place to another. The best advice I can give is to look at all your contributing factors and assess where your organization falls short. Use these findings as a guide for where to focus your improvement efforts. The only way you know how to improve is to measure the cause of problems and target interventions right to them."

No disclosures were reported.

Colorectal surgical site infections dropped by an average of 32% among hospitals that participated in a project designed to reduce facility-specific infection risk factors.

The project – co-sponsored by the Joint Commission Center for Transforming Healthcare and the American College of Surgeons – will result in a user-friendly online tool that can examine any hospital’s infections data and recommend detailed, site-specific interventions.

The commission’s Targeted Solutions Tool should be available by the middle of 2013.

"The hospitals we engaged have mastered these sophisticated change tools, and now we need to make sure this learning can be spread to others," Dr. Mark Chassin said during a press briefing. "[The new tool] will be a very easy-to-follow approach that applies all the lessons we learned – showing how to measure infection rates, figure out which contributing factors are present in their institution, and guiding them through implementations proven to address these factors."

The commission chose to tackle colorectal surgical site infections (SSIs) because they are common, dangerous, and expensive, said Dr. Chassin, president of the group. Unfortunately, risk factors don’t respond to a "one size fits all" prevention protocol. "These factors are highly variable across hospitals, suggesting that there are opportunities to improve performance."

The 2-year pilot project included seven hospitals of varying size and community demographics. The facilities tracked their colorectal SSI patterns using the American College of Surgeons National Surgical Quality Improvement Program. Each hospital then developed interventions targeted at their individual modifiable risk factors, implemented the changes, and recorded their results.

Overall, the protocol reduced colorectal SSIs by 32% – from an average of 16% to 11%. Superficial skin SSIs fell by an average of 45% over the entire study group.

The protocol improved other outcomes as well, Dr. Chassin said. The average length of stay for a colorectal surgery patient with a wound infection decreased from 15 to 13 days. Across the group, the changes were associated with a savings of almost $4 million.

The hospitals collectively identified 34 factors that greatly increased the risk of such infections. During the briefing, Dr. Jenna Lovely, the surgical pharmacotherapy manager at the Mayo Clinic, Rochester, Minn., shared some of their results (J. Am. Coll. Surg. 2011;213:83-92; 2012 [doi:10.1016/j.jamcollsurg.2012.09.009]).

Before implementation of the program, the colorectal SSI rate at Mayo was 10%. With a goal of reducing that number by at least 50%, the team examined risk factors in the preoperative, intraoperative, postoperative, and posthospitalization periods and made some changes, Dr. Lovely said.

Preoperatively, every patient now takes a shower with soap or with a chlorhexidine-based cleanser both the night before and the day of surgery.

Intraoperatively, the site is prepped with an antimicrobial cleansing agent, and the correct antibiotic is administered at 1 hour before the incision is made. If the surgery lasts more than 4 hours, a second dose of the same antibiotic is administered; cefazolin is given 24 hours after closing.

At fascia closing, the surgeon dons a complete change of gown, mask, and gloves. Closing is performed with the use of an entirely new set of instruments.

Postoperatively, everyone who comes in contact with the wound – including staff, the patient, and visitors – practices good hand hygiene. Reminder notes and hand cleanser are located prominently in rooms and all around the unit. Nurses are empowered to change dressings as needed. Wound probing occurs as needed to help expel any contaminated fluids.

Patients are discharged with infection control education and a bottle of chlorhexidine cleanser.

"These changes are embedded in the environment across the continuum of care. It’s part of the surgical unit’s culture, and this makes it easier to do the right thing. The changes also allow the surgeon to focus on doing what he does best – providing a timely and efficient surgery with the best possible outcome," Dr. Lovely said.

Implementation of these changes led to a reduction in SSI rate from 10% to 4%, and that rate has maintained this rate for 18 months.

Dr. Shirin Towfigh, a surgeon at Cedars-Sinai Medical Center in Los Angeles, said her unit experienced a similar improvement.

The project included 46 surgeons and all of the unit staff. Because the team didn’t want to dictate surgical technique, she said, their goal "was to come up with processes that would improve results independent of a surgeon’s practice. We wanted the changes to be effective, but also easy for surgeons to implement in their own practice."

By the end of the study period, the unit’s colorectal SSI rate had decreased by 50%. Since the project closed 6 months ago, that has further improved, with a total decrease of 65%.

"This is a problem colorectal surgeons have been struggling with for years," Dr. Chassin said. "We’ve always tried to get at it with the simple answer: ‘Here are 5 or 10 things everyone should do to decrease SSIs.’ That doesn’t work, because the critical factors that explain poor outcomes differ from one place to another. The best advice I can give is to look at all your contributing factors and assess where your organization falls short. Use these findings as a guide for where to focus your improvement efforts. The only way you know how to improve is to measure the cause of problems and target interventions right to them."

No disclosures were reported.

SAN ANTONIO – The 10-year incidence of leukemia after adjuvant chemotherapy for breast cancer appears to hover around 0.5%, twice as high as previously reported.

A review of more than 20,000 patient records included in the National Comprehensive Cancer Network (NCCN) database found 51 cases of leukemia that developed within 10 years of treatment. Women who had only chemotherapy were at the greatest risk – almost six times more likely to develop the disease than the surgery-only control group, Dr. Antonio Wolff said at that annual San Antonio Breast Cancer Symposium.

"We know that the observed survival benefit with adjuvant therapy does take into account the potential mortality associated with leukemia," said Dr. Wolff of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. "But often we are in the situation where we make the decision to give chemotherapy ‘just because.’ We need to be very careful here, because some of those patients will potentially derive none of the benefits of chemo, and be at risk of its toxicities."

Dr. Wolff and colleagues examined the 1997-2008 data from eight facilities in the NCCN database – a total of 20,533 women with a first diagnosis of breast cancer. The median follow-up was 5 years, but some data were available for up to 15 years after treatment.

About half of the cohort had stage I disease; in most, the cancer was invasive ductal. Slightly more than half had hormone receptor–positive/HER2 negative disease.

The only baseline characteristic significantly different between the groups was age. Women who developed leukemia were significantly older at the time of their cancer treatment (60 vs. 54 years; P = .02); 78% of those with leukemia were older than 50 years.

Of the 51 cases, 44 were acute myeloid leukemia (AML), with a median onset time of 3.5 years after treatment. One-third of these occurred in women with a family history of breast or ovarian cancer. The median time to onset in the AML cases was 2 years.

None of the tumor characteristics were significantly associated with the development of leukemia. There were no significant differences among those who had breast-conserving surgery, mastectomy, or no surgery; or between those who had no radiation therapy, radiation without surgery, radiation after breast-conserving surgery, or radiation after mastectomy, though larger numbers of patients are needed for some of these smaller subset analyses.

The overall rate of leukemia per 1,000 patient/years was 0.46; in the surgery-only group, the rate was 0.16 per 1,000 patient-years. "Of interest is that the rates in each of the treatment groups were similar to the overall rate," – 0.43 in the radiation-only group, 0.52 in the chemotherapy-only group, and 0.54 in the combination therapy group.

At 5 years, the cumulative incidence of leukemia was 0.05% in the surgery-only group; 0.19% in the radiation-only group; 0.30% in the chemotherapy-only group; and 0.32% in the combination therapy group.

But the onset accelerated over the study period, Dr. Wolff noted, with the bulk of cases developing from years 6 to 10. .By the end of the 10-year period, the incidence was 0.2% in the surgery-only group; 0.44% in the radiation-only group; 0.52% in the chemotherapy group; and 0.51% in the combination group.

In a risk analysis using surgery as the control, the overall hazard ratio of leukemia was 2.7 in the radiation-only group; 5.68 in the chemotherapy only group; and 5.64 in the combination group.

Radiation appeared to confer no significant additional risk when it was combined with chemotherapy, Dr. Wolff added.

The findings are strikingly different than previously identified. The largest study of the association was published in 2003, when researchers from the National Surgical Adjuvant Breast and Bowel Project Operations Center reviewed six trials that examined rates of acute myeloid leukemia and myelodysplastic syndrome after doxorubicin and cyclophosphamide therapy (Clin. Breast Cancer 2003;4:273-9).

The subgroup that received anthracycline/cyclophosphamide in that review had a cumulative 8-year incidence of 0.24%. In Dr. Wolff’s chemotherapy subgroup, the cumulative 8-year incidence was 0.52%.

"It’s very important to keep in mind that the known leukemia latency period for anthracycline is 1-3 years, but that of alkylating drugs like cyclophosphamide is 4-6 years and there are case reports of it developing after 10 years," he said. "We need to be very careful when we talk about survival at 5 years vs. 10 years in exposed patients, because they could be at risk for a decade and, potentially, even longer."

SAN ANTONIO – The 10-year incidence of leukemia after adjuvant chemotherapy for breast cancer appears to hover around 0.5%, twice as high as previously reported.

A review of more than 20,000 patient records included in the National Comprehensive Cancer Network (NCCN) database found 51 cases of leukemia that developed within 10 years of treatment. Women who had only chemotherapy were at the greatest risk – almost six times more likely to develop the disease than the surgery-only control group, Dr. Antonio Wolff said at that annual San Antonio Breast Cancer Symposium.

"We know that the observed survival benefit with adjuvant therapy does take into account the potential mortality associated with leukemia," said Dr. Wolff of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. "But often we are in the situation where we make the decision to give chemotherapy ‘just because.’ We need to be very careful here, because some of those patients will potentially derive none of the benefits of chemo, and be at risk of its toxicities."

Dr. Wolff and colleagues examined the 1997-2008 data from eight facilities in the NCCN database – a total of 20,533 women with a first diagnosis of breast cancer. The median follow-up was 5 years, but some data were available for up to 15 years after treatment.

About half of the cohort had stage I disease; in most, the cancer was invasive ductal. Slightly more than half had hormone receptor–positive/HER2 negative disease.

The only baseline characteristic significantly different between the groups was age. Women who developed leukemia were significantly older at the time of their cancer treatment (60 vs. 54 years; P = .02); 78% of those with leukemia were older than 50 years.

Of the 51 cases, 44 were acute myeloid leukemia (AML), with a median onset time of 3.5 years after treatment. One-third of these occurred in women with a family history of breast or ovarian cancer. The median time to onset in the AML cases was 2 years.

None of the tumor characteristics were significantly associated with the development of leukemia. There were no significant differences among those who had breast-conserving surgery, mastectomy, or no surgery; or between those who had no radiation therapy, radiation without surgery, radiation after breast-conserving surgery, or radiation after mastectomy, though larger numbers of patients are needed for some of these smaller subset analyses.

The overall rate of leukemia per 1,000 patient/years was 0.46; in the surgery-only group, the rate was 0.16 per 1,000 patient-years. "Of interest is that the rates in each of the treatment groups were similar to the overall rate," – 0.43 in the radiation-only group, 0.52 in the chemotherapy-only group, and 0.54 in the combination therapy group.

At 5 years, the cumulative incidence of leukemia was 0.05% in the surgery-only group; 0.19% in the radiation-only group; 0.30% in the chemotherapy-only group; and 0.32% in the combination therapy group.

But the onset accelerated over the study period, Dr. Wolff noted, with the bulk of cases developing from years 6 to 10. .By the end of the 10-year period, the incidence was 0.2% in the surgery-only group; 0.44% in the radiation-only group; 0.52% in the chemotherapy group; and 0.51% in the combination group.

In a risk analysis using surgery as the control, the overall hazard ratio of leukemia was 2.7 in the radiation-only group; 5.68 in the chemotherapy only group; and 5.64 in the combination group.

Radiation appeared to confer no significant additional risk when it was combined with chemotherapy, Dr. Wolff added.

The findings are strikingly different than previously identified. The largest study of the association was published in 2003, when researchers from the National Surgical Adjuvant Breast and Bowel Project Operations Center reviewed six trials that examined rates of acute myeloid leukemia and myelodysplastic syndrome after doxorubicin and cyclophosphamide therapy (Clin. Breast Cancer 2003;4:273-9).

The subgroup that received anthracycline/cyclophosphamide in that review had a cumulative 8-year incidence of 0.24%. In Dr. Wolff’s chemotherapy subgroup, the cumulative 8-year incidence was 0.52%.

"It’s very important to keep in mind that the known leukemia latency period for anthracycline is 1-3 years, but that of alkylating drugs like cyclophosphamide is 4-6 years and there are case reports of it developing after 10 years," he said. "We need to be very careful when we talk about survival at 5 years vs. 10 years in exposed patients, because they could be at risk for a decade and, potentially, even longer."

SAN ANTONIO – The 10-year incidence of leukemia after adjuvant chemotherapy for breast cancer appears to hover around 0.5%, twice as high as previously reported.

A review of more than 20,000 patient records included in the National Comprehensive Cancer Network (NCCN) database found 51 cases of leukemia that developed within 10 years of treatment. Women who had only chemotherapy were at the greatest risk – almost six times more likely to develop the disease than the surgery-only control group, Dr. Antonio Wolff said at that annual San Antonio Breast Cancer Symposium.

"We know that the observed survival benefit with adjuvant therapy does take into account the potential mortality associated with leukemia," said Dr. Wolff of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. "But often we are in the situation where we make the decision to give chemotherapy ‘just because.’ We need to be very careful here, because some of those patients will potentially derive none of the benefits of chemo, and be at risk of its toxicities."

Dr. Wolff and colleagues examined the 1997-2008 data from eight facilities in the NCCN database – a total of 20,533 women with a first diagnosis of breast cancer. The median follow-up was 5 years, but some data were available for up to 15 years after treatment.

About half of the cohort had stage I disease; in most, the cancer was invasive ductal. Slightly more than half had hormone receptor–positive/HER2 negative disease.

The only baseline characteristic significantly different between the groups was age. Women who developed leukemia were significantly older at the time of their cancer treatment (60 vs. 54 years; P = .02); 78% of those with leukemia were older than 50 years.

Of the 51 cases, 44 were acute myeloid leukemia (AML), with a median onset time of 3.5 years after treatment. One-third of these occurred in women with a family history of breast or ovarian cancer. The median time to onset in the AML cases was 2 years.

None of the tumor characteristics were significantly associated with the development of leukemia. There were no significant differences among those who had breast-conserving surgery, mastectomy, or no surgery; or between those who had no radiation therapy, radiation without surgery, radiation after breast-conserving surgery, or radiation after mastectomy, though larger numbers of patients are needed for some of these smaller subset analyses.

The overall rate of leukemia per 1,000 patient/years was 0.46; in the surgery-only group, the rate was 0.16 per 1,000 patient-years. "Of interest is that the rates in each of the treatment groups were similar to the overall rate," – 0.43 in the radiation-only group, 0.52 in the chemotherapy-only group, and 0.54 in the combination therapy group.

At 5 years, the cumulative incidence of leukemia was 0.05% in the surgery-only group; 0.19% in the radiation-only group; 0.30% in the chemotherapy-only group; and 0.32% in the combination therapy group.

But the onset accelerated over the study period, Dr. Wolff noted, with the bulk of cases developing from years 6 to 10. .By the end of the 10-year period, the incidence was 0.2% in the surgery-only group; 0.44% in the radiation-only group; 0.52% in the chemotherapy group; and 0.51% in the combination group.

In a risk analysis using surgery as the control, the overall hazard ratio of leukemia was 2.7 in the radiation-only group; 5.68 in the chemotherapy only group; and 5.64 in the combination group.

Radiation appeared to confer no significant additional risk when it was combined with chemotherapy, Dr. Wolff added.

The findings are strikingly different than previously identified. The largest study of the association was published in 2003, when researchers from the National Surgical Adjuvant Breast and Bowel Project Operations Center reviewed six trials that examined rates of acute myeloid leukemia and myelodysplastic syndrome after doxorubicin and cyclophosphamide therapy (Clin. Breast Cancer 2003;4:273-9).

The subgroup that received anthracycline/cyclophosphamide in that review had a cumulative 8-year incidence of 0.24%. In Dr. Wolff’s chemotherapy subgroup, the cumulative 8-year incidence was 0.52%.

"It’s very important to keep in mind that the known leukemia latency period for anthracycline is 1-3 years, but that of alkylating drugs like cyclophosphamide is 4-6 years and there are case reports of it developing after 10 years," he said. "We need to be very careful when we talk about survival at 5 years vs. 10 years in exposed patients, because they could be at risk for a decade and, potentially, even longer."

SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.

The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)

© SABCS/Todd Buchanan 2012

Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.

"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.

The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).

All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.

The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.

Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.

Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).

Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).

There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).

Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.

Dr. Martin is on the speakers bureau and a consultant for Roche.

SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.

The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)

© SABCS/Todd Buchanan 2012

Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.

"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.

The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).

All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.

The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.

Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.

Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).

Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).

There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).

Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.

Dr. Martin is on the speakers bureau and a consultant for Roche.

SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.

The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)

© SABCS/Todd Buchanan 2012

Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.

"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.

The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).

All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.

The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.

Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.

Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).

Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).

There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).

Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.

Dr. Martin is on the speakers bureau and a consultant for Roche.

SAN ANTONIO – Black women are significantly less likely to receive a sentinel lymph node biopsy than are white women – and significantly more likely to develop lymphedema, a large database study has determined.

Among more than 31,000 women with invasive breast cancer diagnosed from 2002-2007, 62% of black women underwent the procedure, compared with 74% of white women – a significant difference (P less than .001).

That disparity led to a doubling in the risk of lymphedema in black women, compared with white women, Dr. Dalliah Black said at the San Antonio Breast Cancer Symposium. Axillary sentinel lymph node biopsy (SLNB) is a less-invasive alternative to axillary lymph node dissection (ALND) for breast cancer staging.

The disparity appears to be regional, said Dr. Black of the University of Texas M.D. Anderson Cancer Center in Houston. A preliminary subanalysis of 12 regions in the database found that Louisiana had the lowest rate of sentinel node biopsy among blacks (58%), while Seattle had the highest (89%). Regional differences were related not only to the patient’s socioeconomic status but to the numbers of surgeons available in the region.

Dr. Black used data extracted from the U.S. national Surveillance, Epidemiology, and End Results (SEER) database. The patient group consisted of 31,274 women diagnosed between 2002 and 2007. All patients had invasive breast cancer with no evidence of distant metastasis and underwent a documented axillary surgical procedure. All of the patients had fee-for-service coverage.

Black women composed 6% of the group (1,767). The median age was 74 years; 75% of the patients had a tumor size of 2 cm or smaller. Most (62%) had undergone a lumpectomy, and 73%, a sentinel lymph node biopsy.

The median number of sentinel nodes removed was two, and the median number of axillary nodes, 11.

The rate of sentinel node biopsy increased in both groups over the study period, as the surgery moved from being an alternate management approach to the preferred approach. But the disparity persisted, Dr. Black said. By 2007, the biopsy rate was 70% among black women and 83% among white (P less than .001).

The difference in SLND was also associated with a significantly increased rate of lymphedema. By 5 years after surgery, lymphedema had developed in 18% of black women who had an axillary node biopsy compared with 7% of white women who had a sentinel node biopsy. But when black women had a sentinel node biopsy, their 5-year rate of lymphedema was similar to the rate among white women (9%; P less than .001).

"This shows that if black women had gotten the appropriate surgery, they were not at any increased risk for lymphedema," Dr. Black said.

She intends to reanalyze the groups when the 2010 SEER data is released next spring. "We hope to see the disparity reduced in that analysis, although it may not be," she said in an interview. "If it’s not, we really need to figure out how we can work with national programs to disseminate guidelines and provide reminders to surgeons and multispecialist breast cancer teams – as well as to patients, so they can advocate for themselves. But it’s not only the patient’s responsibility. It’s a two-way street. We need to take some responsibility for this problem."

Dr. Black has no relevant financial relationships to disclose.

SAN ANTONIO – Black women are significantly less likely to receive a sentinel lymph node biopsy than are white women – and significantly more likely to develop lymphedema, a large database study has determined.

Among more than 31,000 women with invasive breast cancer diagnosed from 2002-2007, 62% of black women underwent the procedure, compared with 74% of white women – a significant difference (P less than .001).

That disparity led to a doubling in the risk of lymphedema in black women, compared with white women, Dr. Dalliah Black said at the San Antonio Breast Cancer Symposium. Axillary sentinel lymph node biopsy (SLNB) is a less-invasive alternative to axillary lymph node dissection (ALND) for breast cancer staging.

The disparity appears to be regional, said Dr. Black of the University of Texas M.D. Anderson Cancer Center in Houston. A preliminary subanalysis of 12 regions in the database found that Louisiana had the lowest rate of sentinel node biopsy among blacks (58%), while Seattle had the highest (89%). Regional differences were related not only to the patient’s socioeconomic status but to the numbers of surgeons available in the region.

Dr. Black used data extracted from the U.S. national Surveillance, Epidemiology, and End Results (SEER) database. The patient group consisted of 31,274 women diagnosed between 2002 and 2007. All patients had invasive breast cancer with no evidence of distant metastasis and underwent a documented axillary surgical procedure. All of the patients had fee-for-service coverage.

Black women composed 6% of the group (1,767). The median age was 74 years; 75% of the patients had a tumor size of 2 cm or smaller. Most (62%) had undergone a lumpectomy, and 73%, a sentinel lymph node biopsy.

The median number of sentinel nodes removed was two, and the median number of axillary nodes, 11.

The rate of sentinel node biopsy increased in both groups over the study period, as the surgery moved from being an alternate management approach to the preferred approach. But the disparity persisted, Dr. Black said. By 2007, the biopsy rate was 70% among black women and 83% among white (P less than .001).

The difference in SLND was also associated with a significantly increased rate of lymphedema. By 5 years after surgery, lymphedema had developed in 18% of black women who had an axillary node biopsy compared with 7% of white women who had a sentinel node biopsy. But when black women had a sentinel node biopsy, their 5-year rate of lymphedema was similar to the rate among white women (9%; P less than .001).

"This shows that if black women had gotten the appropriate surgery, they were not at any increased risk for lymphedema," Dr. Black said.

She intends to reanalyze the groups when the 2010 SEER data is released next spring. "We hope to see the disparity reduced in that analysis, although it may not be," she said in an interview. "If it’s not, we really need to figure out how we can work with national programs to disseminate guidelines and provide reminders to surgeons and multispecialist breast cancer teams – as well as to patients, so they can advocate for themselves. But it’s not only the patient’s responsibility. It’s a two-way street. We need to take some responsibility for this problem."

Dr. Black has no relevant financial relationships to disclose.

SAN ANTONIO – Black women are significantly less likely to receive a sentinel lymph node biopsy than are white women – and significantly more likely to develop lymphedema, a large database study has determined.

Among more than 31,000 women with invasive breast cancer diagnosed from 2002-2007, 62% of black women underwent the procedure, compared with 74% of white women – a significant difference (P less than .001).

That disparity led to a doubling in the risk of lymphedema in black women, compared with white women, Dr. Dalliah Black said at the San Antonio Breast Cancer Symposium. Axillary sentinel lymph node biopsy (SLNB) is a less-invasive alternative to axillary lymph node dissection (ALND) for breast cancer staging.

The disparity appears to be regional, said Dr. Black of the University of Texas M.D. Anderson Cancer Center in Houston. A preliminary subanalysis of 12 regions in the database found that Louisiana had the lowest rate of sentinel node biopsy among blacks (58%), while Seattle had the highest (89%). Regional differences were related not only to the patient’s socioeconomic status but to the numbers of surgeons available in the region.

Dr. Black used data extracted from the U.S. national Surveillance, Epidemiology, and End Results (SEER) database. The patient group consisted of 31,274 women diagnosed between 2002 and 2007. All patients had invasive breast cancer with no evidence of distant metastasis and underwent a documented axillary surgical procedure. All of the patients had fee-for-service coverage.

Black women composed 6% of the group (1,767). The median age was 74 years; 75% of the patients had a tumor size of 2 cm or smaller. Most (62%) had undergone a lumpectomy, and 73%, a sentinel lymph node biopsy.

The median number of sentinel nodes removed was two, and the median number of axillary nodes, 11.

The rate of sentinel node biopsy increased in both groups over the study period, as the surgery moved from being an alternate management approach to the preferred approach. But the disparity persisted, Dr. Black said. By 2007, the biopsy rate was 70% among black women and 83% among white (P less than .001).

The difference in SLND was also associated with a significantly increased rate of lymphedema. By 5 years after surgery, lymphedema had developed in 18% of black women who had an axillary node biopsy compared with 7% of white women who had a sentinel node biopsy. But when black women had a sentinel node biopsy, their 5-year rate of lymphedema was similar to the rate among white women (9%; P less than .001).

"This shows that if black women had gotten the appropriate surgery, they were not at any increased risk for lymphedema," Dr. Black said.

She intends to reanalyze the groups when the 2010 SEER data is released next spring. "We hope to see the disparity reduced in that analysis, although it may not be," she said in an interview. "If it’s not, we really need to figure out how we can work with national programs to disseminate guidelines and provide reminders to surgeons and multispecialist breast cancer teams – as well as to patients, so they can advocate for themselves. But it’s not only the patient’s responsibility. It’s a two-way street. We need to take some responsibility for this problem."

Dr. Black has no relevant financial relationships to disclose.

SAN ANTONIO – Women with breast cancer shouldn't have to relinquish the life-affirming power of sexual intimacy.

Breast cancer brings many challenges that can relegate sexual health to the bottom of the problem list, but helping women preserve or regain that facet of the lives is an important part of a holistic treatment plan, Dr. Michael L. Krychman said at the San Antonio Breast Cancer Symposium.

Nick Piegari/IMNG Medical Media

Unfortunately, most plans don’t include any discussion of sexual intimacy and many women don’t broach the subject alone, said Dr. Krychman, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, and a clinical professor at the University of California, Irvine.

"We now recognize that cancer can be a chronic disease that our patients can often live with for a very long time. Intimacy and relationships are very important for women, as they progress through their cancer care," he noted.

‘Just Be Glad You’re Alive’

Breast cancer patients don’t always get the kind of team approach afforded to those with other illnesses, he said.

"When a patient has diabetes, the treatment team includes an endocrinologist, a dietitian. There are lifestyle changes, foot exams, eye exams. It’s a team approach designed to target and improve every area the disorder affects. But when we talk about sexuality and breast cancer, the reaction often is, ‘Just be glad you’re alive.’ Women can be told to just say goodbye to that part of their lives."

It doesn’t have to be that way, said Dr. Krychman, who spoke at a session on breast cancer survivorship.

"We need to get past this problem with talking about women’s sexuality. Women are embarrassed to bring it up, and when they do they’re often subjected to a paternalistic reaction" that sends a very clear negative message about their feeling and desires, he said.

Addressing sexuality, however, isn’t just about helping women feel good emotionally. It also can be about helping women stay compliant with the drugs that keep them physically healthy.

"One woman came to me after she stopped taking her maintenance therapy because of the effect it was having on her sex life," Dr. Krychman said. "She told me, ‘I’d rather have 5 years of a life lived in color than 10 years of a life lived in shadow.’ "

He was able to convince her that she could have both the years and the enjoyment of those years.

"I follow what I call a conservative-aggressive approach. We start with the conservative interventions, like addressing vaginal dryness and atrophy with moisturizers and lubricants, getting back on a healthy diet, and exercising. But we don’t send a woman away with a bottle of lubricant and say, ‘Come back in 6 months.’ We like to see patients at least once a month to check on progress, and if things aren’t going well we move on to something more," he explained.

Topical estrogens are the go-to treatment for sexual problems in women without cancer, but the jury is still out on whether they are good for women with breast cancer. "We now know that topical may not really be just topical. Hormones can be absorbed systemically even in the small doses seen in vaginal preparations."

Nonhormonal Drugs in the Pipeline

But two nonhormonal drugs in development – flibanserin and bremelanotide – could be promising treatments, Dr. Krychman said.

Flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, has been studied in more than 10,000 women and shown to increase libido and response in those with female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD).

In 2010, the Food and Drug Administration refused to approve it, saying that the side effects of dizziness, nausea, and vomiting seemed to outweigh its benefits.

Last year, however, Sprout Pharmaceuticals of Raleigh, N.C., purchased the drug and raised $20 million for its further development. The company is planning to resubmit data from the 14 existing trials, along with a new validation study, next year.

In October, a 12-month open-label extension study in 1,723 women reported some positive results. By 52 weeks, HSDD symptoms had fallen to remission levels in 90% of the group (J. Sex. Med. 2012 Oct 11. [doi:10.1111/j.1743-6109.2012.02942.x.]).

Bremelanotide is another promising drug, Dr. Krychman said. Like flibanserin, the melanocortin receptor 4 agonist got a new lease on life after the FDA nipped its development in 2007. At that point, the drug was being investigated for erectile dysfunction and female sexual dysfunction in both pre- and postmenopausal women. It was formulated as an intranasal powder but caused blood pressure spikes in some of the men who used it. FDA rejected the initial application as a libido-boosting drug but didn’t rule out its development for other purposes.

Palatin Technologies, the New Jersey company developing the drug, reformulated it into a subcutaneous injection, which did not affect blood pressure in new safety studies. On that basis, Palatin went ahead with a phase IIB trial in 327 premenopausal women with FSAD, HSDD, or both. The company announced positive results last month.

According to a statement, "[the results] demonstrate that women taking bremelanotide showed clinically meaningful and statistically significant increases in the number of satisfying sexual events and also showed clinically meaningful and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared to placebo."

There were no blood pressure problems, although some women did quit the drug because of nausea and vomiting of mild to moderate intensity. Palatin intends to launch a phase III trial next year.

Dr. Krychman has disclosed that he is a consultant/advisor for Warner Chilcott, Pfizer, and Sprout.

SAN ANTONIO – Women with breast cancer shouldn't have to relinquish the life-affirming power of sexual intimacy.

Breast cancer brings many challenges that can relegate sexual health to the bottom of the problem list, but helping women preserve or regain that facet of the lives is an important part of a holistic treatment plan, Dr. Michael L. Krychman said at the San Antonio Breast Cancer Symposium.

Nick Piegari/IMNG Medical Media

Unfortunately, most plans don’t include any discussion of sexual intimacy and many women don’t broach the subject alone, said Dr. Krychman, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, and a clinical professor at the University of California, Irvine.

"We now recognize that cancer can be a chronic disease that our patients can often live with for a very long time. Intimacy and relationships are very important for women, as they progress through their cancer care," he noted.

‘Just Be Glad You’re Alive’

Breast cancer patients don’t always get the kind of team approach afforded to those with other illnesses, he said.

"When a patient has diabetes, the treatment team includes an endocrinologist, a dietitian. There are lifestyle changes, foot exams, eye exams. It’s a team approach designed to target and improve every area the disorder affects. But when we talk about sexuality and breast cancer, the reaction often is, ‘Just be glad you’re alive.’ Women can be told to just say goodbye to that part of their lives."

It doesn’t have to be that way, said Dr. Krychman, who spoke at a session on breast cancer survivorship.

"We need to get past this problem with talking about women’s sexuality. Women are embarrassed to bring it up, and when they do they’re often subjected to a paternalistic reaction" that sends a very clear negative message about their feeling and desires, he said.

Addressing sexuality, however, isn’t just about helping women feel good emotionally. It also can be about helping women stay compliant with the drugs that keep them physically healthy.

"One woman came to me after she stopped taking her maintenance therapy because of the effect it was having on her sex life," Dr. Krychman said. "She told me, ‘I’d rather have 5 years of a life lived in color than 10 years of a life lived in shadow.’ "

He was able to convince her that she could have both the years and the enjoyment of those years.

"I follow what I call a conservative-aggressive approach. We start with the conservative interventions, like addressing vaginal dryness and atrophy with moisturizers and lubricants, getting back on a healthy diet, and exercising. But we don’t send a woman away with a bottle of lubricant and say, ‘Come back in 6 months.’ We like to see patients at least once a month to check on progress, and if things aren’t going well we move on to something more," he explained.

Topical estrogens are the go-to treatment for sexual problems in women without cancer, but the jury is still out on whether they are good for women with breast cancer. "We now know that topical may not really be just topical. Hormones can be absorbed systemically even in the small doses seen in vaginal preparations."

Nonhormonal Drugs in the Pipeline

But two nonhormonal drugs in development – flibanserin and bremelanotide – could be promising treatments, Dr. Krychman said.

Flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, has been studied in more than 10,000 women and shown to increase libido and response in those with female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD).

In 2010, the Food and Drug Administration refused to approve it, saying that the side effects of dizziness, nausea, and vomiting seemed to outweigh its benefits.

Last year, however, Sprout Pharmaceuticals of Raleigh, N.C., purchased the drug and raised $20 million for its further development. The company is planning to resubmit data from the 14 existing trials, along with a new validation study, next year.

In October, a 12-month open-label extension study in 1,723 women reported some positive results. By 52 weeks, HSDD symptoms had fallen to remission levels in 90% of the group (J. Sex. Med. 2012 Oct 11. [doi:10.1111/j.1743-6109.2012.02942.x.]).

Bremelanotide is another promising drug, Dr. Krychman said. Like flibanserin, the melanocortin receptor 4 agonist got a new lease on life after the FDA nipped its development in 2007. At that point, the drug was being investigated for erectile dysfunction and female sexual dysfunction in both pre- and postmenopausal women. It was formulated as an intranasal powder but caused blood pressure spikes in some of the men who used it. FDA rejected the initial application as a libido-boosting drug but didn’t rule out its development for other purposes.

Palatin Technologies, the New Jersey company developing the drug, reformulated it into a subcutaneous injection, which did not affect blood pressure in new safety studies. On that basis, Palatin went ahead with a phase IIB trial in 327 premenopausal women with FSAD, HSDD, or both. The company announced positive results last month.

According to a statement, "[the results] demonstrate that women taking bremelanotide showed clinically meaningful and statistically significant increases in the number of satisfying sexual events and also showed clinically meaningful and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared to placebo."

There were no blood pressure problems, although some women did quit the drug because of nausea and vomiting of mild to moderate intensity. Palatin intends to launch a phase III trial next year.

Dr. Krychman has disclosed that he is a consultant/advisor for Warner Chilcott, Pfizer, and Sprout.

SAN ANTONIO – Women with breast cancer shouldn't have to relinquish the life-affirming power of sexual intimacy.

Breast cancer brings many challenges that can relegate sexual health to the bottom of the problem list, but helping women preserve or regain that facet of the lives is an important part of a holistic treatment plan, Dr. Michael L. Krychman said at the San Antonio Breast Cancer Symposium.

Nick Piegari/IMNG Medical Media

Unfortunately, most plans don’t include any discussion of sexual intimacy and many women don’t broach the subject alone, said Dr. Krychman, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, and a clinical professor at the University of California, Irvine.

"We now recognize that cancer can be a chronic disease that our patients can often live with for a very long time. Intimacy and relationships are very important for women, as they progress through their cancer care," he noted.

‘Just Be Glad You’re Alive’

Breast cancer patients don’t always get the kind of team approach afforded to those with other illnesses, he said.

"When a patient has diabetes, the treatment team includes an endocrinologist, a dietitian. There are lifestyle changes, foot exams, eye exams. It’s a team approach designed to target and improve every area the disorder affects. But when we talk about sexuality and breast cancer, the reaction often is, ‘Just be glad you’re alive.’ Women can be told to just say goodbye to that part of their lives."

It doesn’t have to be that way, said Dr. Krychman, who spoke at a session on breast cancer survivorship.

"We need to get past this problem with talking about women’s sexuality. Women are embarrassed to bring it up, and when they do they’re often subjected to a paternalistic reaction" that sends a very clear negative message about their feeling and desires, he said.

Addressing sexuality, however, isn’t just about helping women feel good emotionally. It also can be about helping women stay compliant with the drugs that keep them physically healthy.

"One woman came to me after she stopped taking her maintenance therapy because of the effect it was having on her sex life," Dr. Krychman said. "She told me, ‘I’d rather have 5 years of a life lived in color than 10 years of a life lived in shadow.’ "

He was able to convince her that she could have both the years and the enjoyment of those years.

"I follow what I call a conservative-aggressive approach. We start with the conservative interventions, like addressing vaginal dryness and atrophy with moisturizers and lubricants, getting back on a healthy diet, and exercising. But we don’t send a woman away with a bottle of lubricant and say, ‘Come back in 6 months.’ We like to see patients at least once a month to check on progress, and if things aren’t going well we move on to something more," he explained.

Topical estrogens are the go-to treatment for sexual problems in women without cancer, but the jury is still out on whether they are good for women with breast cancer. "We now know that topical may not really be just topical. Hormones can be absorbed systemically even in the small doses seen in vaginal preparations."

Nonhormonal Drugs in the Pipeline

But two nonhormonal drugs in development – flibanserin and bremelanotide – could be promising treatments, Dr. Krychman said.

Flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, has been studied in more than 10,000 women and shown to increase libido and response in those with female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD).

In 2010, the Food and Drug Administration refused to approve it, saying that the side effects of dizziness, nausea, and vomiting seemed to outweigh its benefits.

Last year, however, Sprout Pharmaceuticals of Raleigh, N.C., purchased the drug and raised $20 million for its further development. The company is planning to resubmit data from the 14 existing trials, along with a new validation study, next year.

In October, a 12-month open-label extension study in 1,723 women reported some positive results. By 52 weeks, HSDD symptoms had fallen to remission levels in 90% of the group (J. Sex. Med. 2012 Oct 11. [doi:10.1111/j.1743-6109.2012.02942.x.]).

Bremelanotide is another promising drug, Dr. Krychman said. Like flibanserin, the melanocortin receptor 4 agonist got a new lease on life after the FDA nipped its development in 2007. At that point, the drug was being investigated for erectile dysfunction and female sexual dysfunction in both pre- and postmenopausal women. It was formulated as an intranasal powder but caused blood pressure spikes in some of the men who used it. FDA rejected the initial application as a libido-boosting drug but didn’t rule out its development for other purposes.

Palatin Technologies, the New Jersey company developing the drug, reformulated it into a subcutaneous injection, which did not affect blood pressure in new safety studies. On that basis, Palatin went ahead with a phase IIB trial in 327 premenopausal women with FSAD, HSDD, or both. The company announced positive results last month.

According to a statement, "[the results] demonstrate that women taking bremelanotide showed clinically meaningful and statistically significant increases in the number of satisfying sexual events and also showed clinically meaningful and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared to placebo."

There were no blood pressure problems, although some women did quit the drug because of nausea and vomiting of mild to moderate intensity. Palatin intends to launch a phase III trial next year.

Dr. Krychman has disclosed that he is a consultant/advisor for Warner Chilcott, Pfizer, and Sprout.

A lower cut-point for diagnosing gestational diabetes is a double-edged sword for clinicians.

Adopting more stringent criteria would triple the number of women identified whose abnormal glucose levels could potentially endanger their health and that of their unborn children. Once diagnosed, they could be treated.

But adopting the proposed criteria would skyrocket the number of diagnosed gestational diabetes cases from about 135,000 to more than 500,000 each year, according to Dr. E. Albert Reece, dean of the University of Maryland School of Medicine, Baltimore.

"It’s quite possible that lowering the diagnostic threshold with these criteria could push the incidence of gestational diabetes from about 7% of all pregnancies to more than 20%," Dr. Reece said in an interview. "With that may come the potential for more cesarean sections and their related adverse consequences. It’s not a case of simply diagnosing earlier – it’s diagnosing earlier with a real potential for increased interventions that bring along their own risks."

The American Diabetes Association adopted the new diagnostic criteria last year (Diabetes Care 2011;34:S11-61). Now, the American College of Obstetricians and Gynecologists is contemplating its own move, and Dr. Reece, a well-respected expert on the topic, is urging caution.

If ACOG were to adopt the criteria, he said, obstetric interventions related to the condition would almost certainly rise. Mothers and babies would be at the most direct risk of any additional procedures, but clinicians will face their own set of problems.

As cesarean sections and other invasive procedures increase, lawsuits go up as well. The possibility of these collateral consequences isn’t the only thing to consider, warned Dr. Reece. Even now, clinicians who care for women with gestational diabetes are hard pressed to keep up with their patient load, let alone the tens of thousands more who would be diagnosed under the new criteria.

Associated costs can’t be ignored either, he said, especially at this crucial time in America’s health care history, when affordable care for everyone is now the law of the land.

In theory, the idea of catching more cases earlier seems sensible. But health care policy should rely on more than theory, said Dr. Reece, who is also the John Z. and Akiko K. Bowers Distinguished Professor of Obstetrics and Gynecology at the university.

"If we could be certain that making this diagnosis earlier would actually improve outcomes, we would have a compelling reason to change. But at this point, many are unconvinced that change would result in improved outcomes."

The current diagnostic threshold for gestational diabetes is a positive result on two or more oral glucose tolerance tests, with glucose levels of more than 180 mg/dL at 1 hour; more than 155 mg/dL at 2 hours; and more than 140 mg/dL at 3 hours. This approach is based on data gathered in the 1970s and 1980s.

More recent data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study Cooperative Research Group suggest that subclinical hyperglycemia affects additional thousands of pregnant women. The study found positive associations between maternal hyperglycemia and increasing rates of large for gestational age neonates, evidence of fetal hyperinsulinemia, neonatal hypoglycemia, and cesarean delivery.

After the study was published in 2008, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) published its new recommendations for the diagnosis and classification of hyperglycemia during pregnancy. Under the new system, gestational diabetes can be diagnosed after a single abnormal oral glucose tolerance test with the threshold of fasting plasma glucose of more than 92 mg/dL, or, after a single oral test, a level of more than 180 mg/dL at 1 hour and more than 152 mg/dL at 2 hours.

"A key argument for changing the current diagnostic guidelines for gestational diabetes in the United States is that a single diagnostic test – by eliminating the screening phase – will be more convenient for the provider and the patient," Dr. Reece wrote in the October issue of the American Journal of Obstetrics and Gynecology (2012 [doi: 10.1016/j.ajog.2012.10.887]). "Furthermore, because it is more user-friendly, it is argued that the one-step diagnostic test also will be much easier to administer and, thus, the earlier diagnosis and treatment of gestational diabetes will lead to more consistent care, better organized research, and, ultimately, to better outcomes for mothers and their babies."

According to the American Diabetes Association, up to 10% of women with gestational diabetes have underlying undiagnosed diabetes, usually type 2. Women who develop gestational diabetes without underlying disease have a 35%-60% chance of developing it over the next 10-20 years.

Studies also are beginning to uncover long-term risks for babies who develop during a hyperglycemic pregnancy. These infants appear to have double the risk of developing childhood obesity and/or metabolic syndrome, laying the foundation for adulthood rife with obesity- and diabetes-related health problems.

But when researchers examine the overall effect of a more stringent screening and diagnostic protocol, the view is somewhat cloudy, Dr. Reece said.

A 2011 study found that treating mild gestational diabetes was a cost-effective way of improving maternal and neonatal outcomes, including decreasing preeclampsia, cesarean sections, macrosomia, shoulder dystocia, permanent and transient brachial plexus injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admissions (Am. J. Obstet. Gynecol. 2011;205:282.e1-7).

But a more recent study found that treating the condition only saves money when considering the mother’s long-term health.

"Our model demonstrates that [the new criteria] are cost-effective only when post-delivery care reduces diabetes incidence," wrote Dr. Erika Werner.

"When post-delivery care was not accomplished, the ... strategy was no longer cost-effective. ... Although there are potential perinatal benefits associated with the [criteria], these benefits alone do not justify the additional cost associated with tripling the number of GDM diagnoses in the U.S.," the authors wrote (Diabetes Care 2012;35:529-35).

The criteria’s biggest financial bang would come from their ability to detect occult diabetes in the mothers, Dr. Werner said in an interview.

"It would allow us to differentiate those women with underlying diabetes from those with only gestational diabetes. We’re missing these women now because very few ever come back for their postnatal diabetes screening," said Dr. Werner, a maternal fetal medicine specialist at Johns Hopkins University, Baltimore. Intervening early can be assumed to save much of the long-term financial costs of type 2 diabetes.

Her cost analysis isn’t set in stone, though, because it couldn’t control for the financial impact of either increased perinatal interventions – like cesarean sections – or the financial impact of preventing fetal consequences. And there’s no way to predict how many women who did develop diabetes postnatally would require insulin or oral medications, and how many could be conservatively managed with diet and exercise.

"We didn’t control for this because there are not data telling us that controlling glucose in pregnancy improves outcomes for women and neonates. The trends are there, but the confidence intervals are not. Any cost analysis is limited by the data that are out there. And in this case, we need more data," she said.

Dr. Reece agreed, saying only large long-term studies could provide enough of the evidence necessary to support changing the diagnostic algorithm.

But, Dr. Werner said, U.S. physicians might be able to learn from their international colleagues. "Some countries are already moving forward with them, and that will give us some of the additional data that we’re looking for."

Australia is one of those countries. The Australasian Diabetes in Pregnancy Society (www.adips.org) adopted the diagnostic criteria earlier this year, said Prof. Robert Moses, director of the Illawarra Diabetes Service in Wollongong, New South Wales. In a March editorial in the journal Diabetes Care, he likened the controversy over the recommendation to "opening Pandora’s box," adding that he supports the change, but that it needs to be thoughtfully applied, in a "clinically responsible way" (2012;35:461-2).

The change is expected to bump up Australia’s gestational diabetes incidence from 10% to 13%, Dr. Moses said in an interview. Any increase in the cost of managing these women and their pregnancies pales beside the clinical alternative.

"The cost of diagnosing and treating women with gestational diabetes is relatively little compared with other health costs. However, there are unfortunately a lot of potential add-on costs. We know that women with gestational diabetes have more interventions, both obstetric and pediatric."

Even considering those costs, ensuring the long-term health of these mothers and babies is a good investment, he said. To put the cost in perspective, "One course of experimental cancer therapy is likely to cost more than testing 1,000 women and treating the 130 with gestational diabetes. It is all a matter of perspective and priority."

He’s glad that Australia chose to move ahead with the change rather than wait for the official numbers to prove that it works.

"Large studies are difficult to initiate and fund. At some stage, common sense has to prevail. Waiting for the results of trials which will not happen in our lifetime should not be an excuse not to give the best possible maternal and fetal care. This is too important a problem to ignore, especially as the solution is relatively simple and the cost is relatively trivial," he said.

None of the sources named disclosed any financial relationships relative to the topic of this article.

A lower cut-point for diagnosing gestational diabetes is a double-edged sword for clinicians.

Adopting more stringent criteria would triple the number of women identified whose abnormal glucose levels could potentially endanger their health and that of their unborn children. Once diagnosed, they could be treated.

But adopting the proposed criteria would skyrocket the number of diagnosed gestational diabetes cases from about 135,000 to more than 500,000 each year, according to Dr. E. Albert Reece, dean of the University of Maryland School of Medicine, Baltimore.

"It’s quite possible that lowering the diagnostic threshold with these criteria could push the incidence of gestational diabetes from about 7% of all pregnancies to more than 20%," Dr. Reece said in an interview. "With that may come the potential for more cesarean sections and their related adverse consequences. It’s not a case of simply diagnosing earlier – it’s diagnosing earlier with a real potential for increased interventions that bring along their own risks."

The American Diabetes Association adopted the new diagnostic criteria last year (Diabetes Care 2011;34:S11-61). Now, the American College of Obstetricians and Gynecologists is contemplating its own move, and Dr. Reece, a well-respected expert on the topic, is urging caution.

If ACOG were to adopt the criteria, he said, obstetric interventions related to the condition would almost certainly rise. Mothers and babies would be at the most direct risk of any additional procedures, but clinicians will face their own set of problems.

As cesarean sections and other invasive procedures increase, lawsuits go up as well. The possibility of these collateral consequences isn’t the only thing to consider, warned Dr. Reece. Even now, clinicians who care for women with gestational diabetes are hard pressed to keep up with their patient load, let alone the tens of thousands more who would be diagnosed under the new criteria.

Associated costs can’t be ignored either, he said, especially at this crucial time in America’s health care history, when affordable care for everyone is now the law of the land.

In theory, the idea of catching more cases earlier seems sensible. But health care policy should rely on more than theory, said Dr. Reece, who is also the John Z. and Akiko K. Bowers Distinguished Professor of Obstetrics and Gynecology at the university.

"If we could be certain that making this diagnosis earlier would actually improve outcomes, we would have a compelling reason to change. But at this point, many are unconvinced that change would result in improved outcomes."

The current diagnostic threshold for gestational diabetes is a positive result on two or more oral glucose tolerance tests, with glucose levels of more than 180 mg/dL at 1 hour; more than 155 mg/dL at 2 hours; and more than 140 mg/dL at 3 hours. This approach is based on data gathered in the 1970s and 1980s.

More recent data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study Cooperative Research Group suggest that subclinical hyperglycemia affects additional thousands of pregnant women. The study found positive associations between maternal hyperglycemia and increasing rates of large for gestational age neonates, evidence of fetal hyperinsulinemia, neonatal hypoglycemia, and cesarean delivery.

After the study was published in 2008, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) published its new recommendations for the diagnosis and classification of hyperglycemia during pregnancy. Under the new system, gestational diabetes can be diagnosed after a single abnormal oral glucose tolerance test with the threshold of fasting plasma glucose of more than 92 mg/dL, or, after a single oral test, a level of more than 180 mg/dL at 1 hour and more than 152 mg/dL at 2 hours.

"A key argument for changing the current diagnostic guidelines for gestational diabetes in the United States is that a single diagnostic test – by eliminating the screening phase – will be more convenient for the provider and the patient," Dr. Reece wrote in the October issue of the American Journal of Obstetrics and Gynecology (2012 [doi: 10.1016/j.ajog.2012.10.887]). "Furthermore, because it is more user-friendly, it is argued that the one-step diagnostic test also will be much easier to administer and, thus, the earlier diagnosis and treatment of gestational diabetes will lead to more consistent care, better organized research, and, ultimately, to better outcomes for mothers and their babies."

According to the American Diabetes Association, up to 10% of women with gestational diabetes have underlying undiagnosed diabetes, usually type 2. Women who develop gestational diabetes without underlying disease have a 35%-60% chance of developing it over the next 10-20 years.

Studies also are beginning to uncover long-term risks for babies who develop during a hyperglycemic pregnancy. These infants appear to have double the risk of developing childhood obesity and/or metabolic syndrome, laying the foundation for adulthood rife with obesity- and diabetes-related health problems.

But when researchers examine the overall effect of a more stringent screening and diagnostic protocol, the view is somewhat cloudy, Dr. Reece said.

A 2011 study found that treating mild gestational diabetes was a cost-effective way of improving maternal and neonatal outcomes, including decreasing preeclampsia, cesarean sections, macrosomia, shoulder dystocia, permanent and transient brachial plexus injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admissions (Am. J. Obstet. Gynecol. 2011;205:282.e1-7).

But a more recent study found that treating the condition only saves money when considering the mother’s long-term health.

"Our model demonstrates that [the new criteria] are cost-effective only when post-delivery care reduces diabetes incidence," wrote Dr. Erika Werner.

"When post-delivery care was not accomplished, the ... strategy was no longer cost-effective. ... Although there are potential perinatal benefits associated with the [criteria], these benefits alone do not justify the additional cost associated with tripling the number of GDM diagnoses in the U.S.," the authors wrote (Diabetes Care 2012;35:529-35).

The criteria’s biggest financial bang would come from their ability to detect occult diabetes in the mothers, Dr. Werner said in an interview.

"It would allow us to differentiate those women with underlying diabetes from those with only gestational diabetes. We’re missing these women now because very few ever come back for their postnatal diabetes screening," said Dr. Werner, a maternal fetal medicine specialist at Johns Hopkins University, Baltimore. Intervening early can be assumed to save much of the long-term financial costs of type 2 diabetes.

Her cost analysis isn’t set in stone, though, because it couldn’t control for the financial impact of either increased perinatal interventions – like cesarean sections – or the financial impact of preventing fetal consequences. And there’s no way to predict how many women who did develop diabetes postnatally would require insulin or oral medications, and how many could be conservatively managed with diet and exercise.

"We didn’t control for this because there are not data telling us that controlling glucose in pregnancy improves outcomes for women and neonates. The trends are there, but the confidence intervals are not. Any cost analysis is limited by the data that are out there. And in this case, we need more data," she said.

Dr. Reece agreed, saying only large long-term studies could provide enough of the evidence necessary to support changing the diagnostic algorithm.

But, Dr. Werner said, U.S. physicians might be able to learn from their international colleagues. "Some countries are already moving forward with them, and that will give us some of the additional data that we’re looking for."

Australia is one of those countries. The Australasian Diabetes in Pregnancy Society (www.adips.org) adopted the diagnostic criteria earlier this year, said Prof. Robert Moses, director of the Illawarra Diabetes Service in Wollongong, New South Wales. In a March editorial in the journal Diabetes Care, he likened the controversy over the recommendation to "opening Pandora’s box," adding that he supports the change, but that it needs to be thoughtfully applied, in a "clinically responsible way" (2012;35:461-2).

The change is expected to bump up Australia’s gestational diabetes incidence from 10% to 13%, Dr. Moses said in an interview. Any increase in the cost of managing these women and their pregnancies pales beside the clinical alternative.

"The cost of diagnosing and treating women with gestational diabetes is relatively little compared with other health costs. However, there are unfortunately a lot of potential add-on costs. We know that women with gestational diabetes have more interventions, both obstetric and pediatric."

Even considering those costs, ensuring the long-term health of these mothers and babies is a good investment, he said. To put the cost in perspective, "One course of experimental cancer therapy is likely to cost more than testing 1,000 women and treating the 130 with gestational diabetes. It is all a matter of perspective and priority."

He’s glad that Australia chose to move ahead with the change rather than wait for the official numbers to prove that it works.

"Large studies are difficult to initiate and fund. At some stage, common sense has to prevail. Waiting for the results of trials which will not happen in our lifetime should not be an excuse not to give the best possible maternal and fetal care. This is too important a problem to ignore, especially as the solution is relatively simple and the cost is relatively trivial," he said.

None of the sources named disclosed any financial relationships relative to the topic of this article.

A lower cut-point for diagnosing gestational diabetes is a double-edged sword for clinicians.

Adopting more stringent criteria would triple the number of women identified whose abnormal glucose levels could potentially endanger their health and that of their unborn children. Once diagnosed, they could be treated.

But adopting the proposed criteria would skyrocket the number of diagnosed gestational diabetes cases from about 135,000 to more than 500,000 each year, according to Dr. E. Albert Reece, dean of the University of Maryland School of Medicine, Baltimore.

"It’s quite possible that lowering the diagnostic threshold with these criteria could push the incidence of gestational diabetes from about 7% of all pregnancies to more than 20%," Dr. Reece said in an interview. "With that may come the potential for more cesarean sections and their related adverse consequences. It’s not a case of simply diagnosing earlier – it’s diagnosing earlier with a real potential for increased interventions that bring along their own risks."

The American Diabetes Association adopted the new diagnostic criteria last year (Diabetes Care 2011;34:S11-61). Now, the American College of Obstetricians and Gynecologists is contemplating its own move, and Dr. Reece, a well-respected expert on the topic, is urging caution.

If ACOG were to adopt the criteria, he said, obstetric interventions related to the condition would almost certainly rise. Mothers and babies would be at the most direct risk of any additional procedures, but clinicians will face their own set of problems.

As cesarean sections and other invasive procedures increase, lawsuits go up as well. The possibility of these collateral consequences isn’t the only thing to consider, warned Dr. Reece. Even now, clinicians who care for women with gestational diabetes are hard pressed to keep up with their patient load, let alone the tens of thousands more who would be diagnosed under the new criteria.

Associated costs can’t be ignored either, he said, especially at this crucial time in America’s health care history, when affordable care for everyone is now the law of the land.

In theory, the idea of catching more cases earlier seems sensible. But health care policy should rely on more than theory, said Dr. Reece, who is also the John Z. and Akiko K. Bowers Distinguished Professor of Obstetrics and Gynecology at the university.

"If we could be certain that making this diagnosis earlier would actually improve outcomes, we would have a compelling reason to change. But at this point, many are unconvinced that change would result in improved outcomes."

The current diagnostic threshold for gestational diabetes is a positive result on two or more oral glucose tolerance tests, with glucose levels of more than 180 mg/dL at 1 hour; more than 155 mg/dL at 2 hours; and more than 140 mg/dL at 3 hours. This approach is based on data gathered in the 1970s and 1980s.

More recent data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study Cooperative Research Group suggest that subclinical hyperglycemia affects additional thousands of pregnant women. The study found positive associations between maternal hyperglycemia and increasing rates of large for gestational age neonates, evidence of fetal hyperinsulinemia, neonatal hypoglycemia, and cesarean delivery.

After the study was published in 2008, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) published its new recommendations for the diagnosis and classification of hyperglycemia during pregnancy. Under the new system, gestational diabetes can be diagnosed after a single abnormal oral glucose tolerance test with the threshold of fasting plasma glucose of more than 92 mg/dL, or, after a single oral test, a level of more than 180 mg/dL at 1 hour and more than 152 mg/dL at 2 hours.

"A key argument for changing the current diagnostic guidelines for gestational diabetes in the United States is that a single diagnostic test – by eliminating the screening phase – will be more convenient for the provider and the patient," Dr. Reece wrote in the October issue of the American Journal of Obstetrics and Gynecology (2012 [doi: 10.1016/j.ajog.2012.10.887]). "Furthermore, because it is more user-friendly, it is argued that the one-step diagnostic test also will be much easier to administer and, thus, the earlier diagnosis and treatment of gestational diabetes will lead to more consistent care, better organized research, and, ultimately, to better outcomes for mothers and their babies."

According to the American Diabetes Association, up to 10% of women with gestational diabetes have underlying undiagnosed diabetes, usually type 2. Women who develop gestational diabetes without underlying disease have a 35%-60% chance of developing it over the next 10-20 years.

Studies also are beginning to uncover long-term risks for babies who develop during a hyperglycemic pregnancy. These infants appear to have double the risk of developing childhood obesity and/or metabolic syndrome, laying the foundation for adulthood rife with obesity- and diabetes-related health problems.

But when researchers examine the overall effect of a more stringent screening and diagnostic protocol, the view is somewhat cloudy, Dr. Reece said.

A 2011 study found that treating mild gestational diabetes was a cost-effective way of improving maternal and neonatal outcomes, including decreasing preeclampsia, cesarean sections, macrosomia, shoulder dystocia, permanent and transient brachial plexus injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admissions (Am. J. Obstet. Gynecol. 2011;205:282.e1-7).

But a more recent study found that treating the condition only saves money when considering the mother’s long-term health.

"Our model demonstrates that [the new criteria] are cost-effective only when post-delivery care reduces diabetes incidence," wrote Dr. Erika Werner.

"When post-delivery care was not accomplished, the ... strategy was no longer cost-effective. ... Although there are potential perinatal benefits associated with the [criteria], these benefits alone do not justify the additional cost associated with tripling the number of GDM diagnoses in the U.S.," the authors wrote (Diabetes Care 2012;35:529-35).

The criteria’s biggest financial bang would come from their ability to detect occult diabetes in the mothers, Dr. Werner said in an interview.

"It would allow us to differentiate those women with underlying diabetes from those with only gestational diabetes. We’re missing these women now because very few ever come back for their postnatal diabetes screening," said Dr. Werner, a maternal fetal medicine specialist at Johns Hopkins University, Baltimore. Intervening early can be assumed to save much of the long-term financial costs of type 2 diabetes.

Her cost analysis isn’t set in stone, though, because it couldn’t control for the financial impact of either increased perinatal interventions – like cesarean sections – or the financial impact of preventing fetal consequences. And there’s no way to predict how many women who did develop diabetes postnatally would require insulin or oral medications, and how many could be conservatively managed with diet and exercise.

"We didn’t control for this because there are not data telling us that controlling glucose in pregnancy improves outcomes for women and neonates. The trends are there, but the confidence intervals are not. Any cost analysis is limited by the data that are out there. And in this case, we need more data," she said.

Dr. Reece agreed, saying only large long-term studies could provide enough of the evidence necessary to support changing the diagnostic algorithm.

But, Dr. Werner said, U.S. physicians might be able to learn from their international colleagues. "Some countries are already moving forward with them, and that will give us some of the additional data that we’re looking for."

Australia is one of those countries. The Australasian Diabetes in Pregnancy Society (www.adips.org) adopted the diagnostic criteria earlier this year, said Prof. Robert Moses, director of the Illawarra Diabetes Service in Wollongong, New South Wales. In a March editorial in the journal Diabetes Care, he likened the controversy over the recommendation to "opening Pandora’s box," adding that he supports the change, but that it needs to be thoughtfully applied, in a "clinically responsible way" (2012;35:461-2).

The change is expected to bump up Australia’s gestational diabetes incidence from 10% to 13%, Dr. Moses said in an interview. Any increase in the cost of managing these women and their pregnancies pales beside the clinical alternative.

"The cost of diagnosing and treating women with gestational diabetes is relatively little compared with other health costs. However, there are unfortunately a lot of potential add-on costs. We know that women with gestational diabetes have more interventions, both obstetric and pediatric."

Even considering those costs, ensuring the long-term health of these mothers and babies is a good investment, he said. To put the cost in perspective, "One course of experimental cancer therapy is likely to cost more than testing 1,000 women and treating the 130 with gestational diabetes. It is all a matter of perspective and priority."

He’s glad that Australia chose to move ahead with the change rather than wait for the official numbers to prove that it works.

"Large studies are difficult to initiate and fund. At some stage, common sense has to prevail. Waiting for the results of trials which will not happen in our lifetime should not be an excuse not to give the best possible maternal and fetal care. This is too important a problem to ignore, especially as the solution is relatively simple and the cost is relatively trivial," he said.

None of the sources named disclosed any financial relationships relative to the topic of this article.

NEW ORLEANS – An electrocardiogram isn’t necessary for student athletes or children taking stimulant medications for attention disorders unless the child has cardiac risk factors or a family history of early-onset heart disease.

ECGs are not always easy to obtain, and they cost parents money, time, and anxiety, Dr. Christopher Snyder said at the annual meeting of the American Academy of Pediatrics. To be really useful, he said, they should be read by a pediatric cardiologist – a specialist in remarkably short supply.

©wakila/istockphotos.com

"Just don’t do it. You don’t need to do it!" said Dr. Snyder, a pediatric cardiologist at the Rainbow Babies and Children’s Hospital in Cleveland.

The American Heart Association (AHA) recommends against routine ECGs in student athletes. The only children who really need the test before playing sports are those with a family or personal history of specific cardiac findings, including:

• Unexplained fainting.

• Excessive fatigue with exercise.

• Abnormal blood pressure.

• Heart murmur.

• A relative who developed or died from heart disease at younger than 50 years.

• Signs of Marfan syndrome.

High school and college athletes should receive a biennial 12-item exam focused on personal and family findings, with a preparticipation history taken between the screenings, the guideline states.

Things aren’t quite so clear-cut with regard to ECGs for children beginning a stimulant medication. "There is no evidence that this is needed, but we do it because we think we should," Dr. Snyder said. Medications for attention-deficit/hyperactivity disorder (ADHD) "have never been shown to cause heart problems, although there might be a slight increase in blood pressure of about 1 mm Hg and a slight increase in heart rate – about 1 beat per minute. Sudden cardiac death has been reported and linked to ADHD medications, but it’s never been proven to have any causal association."

The AHA’s 2008 ADHD medication cardiac screening recommendation contributed to the confusion about the necessity of an ECG for these children, Dr. Snyder said. "It’s not mandatory, and it’s left to the physician’s discretion," but the guideline suggests that an ECG will strengthen the accuracy of any cardiac risk screening.

The minimal screen before starting a stimulant medication should include looking for cardiac structural abnormalities, heart murmurs, hypertension, palpitations, arrhythmia, syncope, signs of Marfan syndrome, and family history, the guideline noted. But, it added, "Some of the cardiac conditions associated with sudden cardiac death might not be detected on a routine physical examination. Therefore it can be useful to add an ECG, which may increase the likelihood of identifying significant conditions ... that are known to be associated with sudden cardiac death."

Despite suggesting ECGs, the AHA guideline gave them a class IIa recommendation and a C evidence level. It also recommended that the test be read by a pediatric cardiologist, and that it might need to be repeated after the onset of puberty, if symptoms develop, or if cardiac problems develop in a family member.

Shortly after the AHA recommendation came out, the American Academy of Pediatrics (AAP) published its own guideline, which called the cardiology paper "controversial" and made clear its disagreement with the guideline.

"The AAP and its constituent groups disagree with the AHA statement as to both the classification and the level of evidence. ... Moreover, the substantial expert opinion and reasoning outlined in the AHA statement suggests that harm outweighs the benefit of recommending routine ECGs for healthy children who are starting stimulant medication for ADHD. Accordingly, the AAP would recommend against such routine ECG screening."

There’s no good evidence that sudden death occurs any more frequently among children taking the medications, AAP asserted. Therefore, a targeted cardiac personal and family history, combined with a thorough physical, is adequate not only to identify any cardiac risk factors, but to pinpoint any other health concerns that might warrant attention.

"Electrocardiography or echocardiography in this population would not otherwise be routine or recommended," according to the AAP statement.

Dr. Snyder did not disclose any relevant financial conflicts.

NEW ORLEANS – An electrocardiogram isn’t necessary for student athletes or children taking stimulant medications for attention disorders unless the child has cardiac risk factors or a family history of early-onset heart disease.

ECGs are not always easy to obtain, and they cost parents money, time, and anxiety, Dr. Christopher Snyder said at the annual meeting of the American Academy of Pediatrics. To be really useful, he said, they should be read by a pediatric cardiologist – a specialist in remarkably short supply.

©wakila/istockphotos.com

"Just don’t do it. You don’t need to do it!" said Dr. Snyder, a pediatric cardiologist at the Rainbow Babies and Children’s Hospital in Cleveland.

The American Heart Association (AHA) recommends against routine ECGs in student athletes. The only children who really need the test before playing sports are those with a family or personal history of specific cardiac findings, including:

• Unexplained fainting.

• Excessive fatigue with exercise.

• Abnormal blood pressure.

• Heart murmur.

• A relative who developed or died from heart disease at younger than 50 years.

• Signs of Marfan syndrome.

High school and college athletes should receive a biennial 12-item exam focused on personal and family findings, with a preparticipation history taken between the screenings, the guideline states.

Things aren’t quite so clear-cut with regard to ECGs for children beginning a stimulant medication. "There is no evidence that this is needed, but we do it because we think we should," Dr. Snyder said. Medications for attention-deficit/hyperactivity disorder (ADHD) "have never been shown to cause heart problems, although there might be a slight increase in blood pressure of about 1 mm Hg and a slight increase in heart rate – about 1 beat per minute. Sudden cardiac death has been reported and linked to ADHD medications, but it’s never been proven to have any causal association."

The AHA’s 2008 ADHD medication cardiac screening recommendation contributed to the confusion about the necessity of an ECG for these children, Dr. Snyder said. "It’s not mandatory, and it’s left to the physician’s discretion," but the guideline suggests that an ECG will strengthen the accuracy of any cardiac risk screening.

The minimal screen before starting a stimulant medication should include looking for cardiac structural abnormalities, heart murmurs, hypertension, palpitations, arrhythmia, syncope, signs of Marfan syndrome, and family history, the guideline noted. But, it added, "Some of the cardiac conditions associated with sudden cardiac death might not be detected on a routine physical examination. Therefore it can be useful to add an ECG, which may increase the likelihood of identifying significant conditions ... that are known to be associated with sudden cardiac death."

Despite suggesting ECGs, the AHA guideline gave them a class IIa recommendation and a C evidence level. It also recommended that the test be read by a pediatric cardiologist, and that it might need to be repeated after the onset of puberty, if symptoms develop, or if cardiac problems develop in a family member.

Shortly after the AHA recommendation came out, the American Academy of Pediatrics (AAP) published its own guideline, which called the cardiology paper "controversial" and made clear its disagreement with the guideline.

"The AAP and its constituent groups disagree with the AHA statement as to both the classification and the level of evidence. ... Moreover, the substantial expert opinion and reasoning outlined in the AHA statement suggests that harm outweighs the benefit of recommending routine ECGs for healthy children who are starting stimulant medication for ADHD. Accordingly, the AAP would recommend against such routine ECG screening."

There’s no good evidence that sudden death occurs any more frequently among children taking the medications, AAP asserted. Therefore, a targeted cardiac personal and family history, combined with a thorough physical, is adequate not only to identify any cardiac risk factors, but to pinpoint any other health concerns that might warrant attention.

"Electrocardiography or echocardiography in this population would not otherwise be routine or recommended," according to the AAP statement.

Dr. Snyder did not disclose any relevant financial conflicts.

NEW ORLEANS – An electrocardiogram isn’t necessary for student athletes or children taking stimulant medications for attention disorders unless the child has cardiac risk factors or a family history of early-onset heart disease.

ECGs are not always easy to obtain, and they cost parents money, time, and anxiety, Dr. Christopher Snyder said at the annual meeting of the American Academy of Pediatrics. To be really useful, he said, they should be read by a pediatric cardiologist – a specialist in remarkably short supply.

©wakila/istockphotos.com

"Just don’t do it. You don’t need to do it!" said Dr. Snyder, a pediatric cardiologist at the Rainbow Babies and Children’s Hospital in Cleveland.

The American Heart Association (AHA) recommends against routine ECGs in student athletes. The only children who really need the test before playing sports are those with a family or personal history of specific cardiac findings, including:

• Unexplained fainting.

• Excessive fatigue with exercise.

• Abnormal blood pressure.

• Heart murmur.

• A relative who developed or died from heart disease at younger than 50 years.

• Signs of Marfan syndrome.

High school and college athletes should receive a biennial 12-item exam focused on personal and family findings, with a preparticipation history taken between the screenings, the guideline states.

Things aren’t quite so clear-cut with regard to ECGs for children beginning a stimulant medication. "There is no evidence that this is needed, but we do it because we think we should," Dr. Snyder said. Medications for attention-deficit/hyperactivity disorder (ADHD) "have never been shown to cause heart problems, although there might be a slight increase in blood pressure of about 1 mm Hg and a slight increase in heart rate – about 1 beat per minute. Sudden cardiac death has been reported and linked to ADHD medications, but it’s never been proven to have any causal association."

The AHA’s 2008 ADHD medication cardiac screening recommendation contributed to the confusion about the necessity of an ECG for these children, Dr. Snyder said. "It’s not mandatory, and it’s left to the physician’s discretion," but the guideline suggests that an ECG will strengthen the accuracy of any cardiac risk screening.

The minimal screen before starting a stimulant medication should include looking for cardiac structural abnormalities, heart murmurs, hypertension, palpitations, arrhythmia, syncope, signs of Marfan syndrome, and family history, the guideline noted. But, it added, "Some of the cardiac conditions associated with sudden cardiac death might not be detected on a routine physical examination. Therefore it can be useful to add an ECG, which may increase the likelihood of identifying significant conditions ... that are known to be associated with sudden cardiac death."

Despite suggesting ECGs, the AHA guideline gave them a class IIa recommendation and a C evidence level. It also recommended that the test be read by a pediatric cardiologist, and that it might need to be repeated after the onset of puberty, if symptoms develop, or if cardiac problems develop in a family member.

Shortly after the AHA recommendation came out, the American Academy of Pediatrics (AAP) published its own guideline, which called the cardiology paper "controversial" and made clear its disagreement with the guideline.

"The AAP and its constituent groups disagree with the AHA statement as to both the classification and the level of evidence. ... Moreover, the substantial expert opinion and reasoning outlined in the AHA statement suggests that harm outweighs the benefit of recommending routine ECGs for healthy children who are starting stimulant medication for ADHD. Accordingly, the AAP would recommend against such routine ECG screening."

There’s no good evidence that sudden death occurs any more frequently among children taking the medications, AAP asserted. Therefore, a targeted cardiac personal and family history, combined with a thorough physical, is adequate not only to identify any cardiac risk factors, but to pinpoint any other health concerns that might warrant attention.

"Electrocardiography or echocardiography in this population would not otherwise be routine or recommended," according to the AAP statement.

Dr. Snyder did not disclose any relevant financial conflicts.

A single, harmonized database for disclosing conflicts of interest could save academic centers, researchers, and the entities that fund their work a myriad of headaches.

Rather than completing disparate disclosure forms for every research application or journal submission, users would enter their baseline information into a central system and update it as needed. Every time the information is required, those who request permission could pull a digital copy and format it according to their needs.

A new system could be launched as early as late 2013 or early 2014, said Dr. Allen Lichter, a member of the committee charged with its framing.

"The time has come for such a harmonized, centralized disclosure system to be created for the benefit of everyone who must produce or receive disclosure information," Dr. Lichter wrote in a viewpoint published Nov. 28 in JAMA (2012;308:2093-94). "Such a system can be designed and implemented as one element in a process to help ensure that research can progress in a trusted, transparent fashion, thereby increasing trust among the public and health care professionals in new medical products that are brought to the benefit of patients."

The centralized system was published in a discussion paper from the Institute of Medicine (IOM), which last year convened a stakeholders’ meeting to explore the possibility.

According to the committee’s paper, a centralized system would be similar to the common application for undergraduate college admission, in which students enter all application and supporting materials in a central database, and can submit that package to any college or university. This benefits students by cutting down on repetitive paperwork, and institutions by allowing receipt of a standardized, digital application.

"The harmonized system must encompass the full scope of reporting indicated by statute and regulation and most, if not all, of the reporting currently requested by organizations," the committee wrote. "A thoughtfully constructed system that meets these needs, allows institutions to filter for information relevant to them, and maintains a nimble updating capacity has the best chance to be broadly accepted by individual and organizational users."

The committee painted with a rather broad brush those who would need to report their financial conflicts of interest. Reporting should be required not only of the physician or researcher, but also of close family members who receive any remuneration that could be construed as a conflict.

Not only would such a system simplify and clarify the disclosure process, it also would fulfill at least some of the requirements of the Physician Payment Sunshine Act, a part of the Affordable Care Act. The Sunshine Act requires manufacturers whose products are covered by federal health care programs including Medicare and Medicaid to report gifts and payments made to teaching hospitals, physicians, and their immediate family members.

That law likely portends a great increase in the complexity of financial disclosure, wrote Dr. Lichter, lead author of the IOM discussion paper.

Before such a system can be designed, however, some groundwork is necessary. Different bodies have different definitions of the same financial reporting requirement. The National Institutes of Health defines it as salary, payment, stocks and options, and ownership. The International Committee of Medical Journal Editors defines it as resources received directly or indirectly that supported work on any given manuscript.

The IOM committees suggested that data be reported separately for each financial relationship, including the beginning and ending dates of the relationship, the name of a drug or device, and the value of each relationship.

Administering the database is an entirely different – and just as complicated – matter, according to the committee. Those who are obliged to report conflicts need to feel confident that their data can’t be compromised, so each person should have full ownership and control of their information.

A centralized system is one option. In this scenario, all data are stored and managed in a single repository from which users could enter and request information. While this would require a large up-front investment, it offers several advantages, the committee said.

• It would be easy to manage and operate.

• It could be easily changed as reporting requirements change.

• When linked to organizational systems, data transfer would be quick and easy.

A second option is a federated system which would link many now-separate databases that would then be available through one portal. Since this approach is based on existing systems, the initial investment would probably be less. However, it would require reconfiguring almost every one of those databases in order to link them.

In either scenario, data should be accessible not only via computer but also via mobile devices.

As with any large project, a harmonized reporting system will create its own personnel requirements, the committee wrote. These could be served by an existing entity, or by something entirely new.

"Creation of a new entity provides the opportunity for de novo formulation of practices and processes; however, the cost may be high. Developing the activity under the roof of an existing organization allows for building on existing infrastructure, thereby decreasing costs up-front. Over time, a freestanding operation could be established if indicated," the committee wrote.

The system would also need the guidance of a secretariat composed of stakeholders. That group would ensure that the database continued to serve members to the fullest.

The committee also addressed funding such centralized system. "The revenue stream ... might flow from several sources: grants from interested organizations and/or philanthropies, membership dues, subscription fees, licensing, or a hybrid of multiple sources."

Subscription fees would likely be tiered, depending on the required level of service. Committee members envisioned this as being similar to the different subscription levels for online income tax programs, with the lowest fee corresponding for the simplest returns.

The current system of repeated and disparate disclosure submissions is destined to become an unwieldy dinosaur, Dr. Lichter wrote in his editorial.

"It would be difficult to imagine a more cumbersome and confusing system, one in which even the most diligent investigator runs the risk of producing an inaccurate report," wrote Dr. Lichter, who is also chief executive officer of the American Society of Clinical Oncology.

Committee meetings will continue, and independent contractors are working on the specific details, according to Dr. Lichter.

"Outside consultants have been engaged to create a full business plan, including the system’s technical specifications, software needs, hosting opportunities, data governance, cost, and opportunities for a revenue stream that would allow the system to self-sustain."

The Institute of Medicine supported the work. Dr. Lichter had no financial disclosures.

A single, harmonized database for disclosing conflicts of interest could save academic centers, researchers, and the entities that fund their work a myriad of headaches.

Rather than completing disparate disclosure forms for every research application or journal submission, users would enter their baseline information into a central system and update it as needed. Every time the information is required, those who request permission could pull a digital copy and format it according to their needs.

A new system could be launched as early as late 2013 or early 2014, said Dr. Allen Lichter, a member of the committee charged with its framing.

"The time has come for such a harmonized, centralized disclosure system to be created for the benefit of everyone who must produce or receive disclosure information," Dr. Lichter wrote in a viewpoint published Nov. 28 in JAMA (2012;308:2093-94). "Such a system can be designed and implemented as one element in a process to help ensure that research can progress in a trusted, transparent fashion, thereby increasing trust among the public and health care professionals in new medical products that are brought to the benefit of patients."

The centralized system was published in a discussion paper from the Institute of Medicine (IOM), which last year convened a stakeholders’ meeting to explore the possibility.

According to the committee’s paper, a centralized system would be similar to the common application for undergraduate college admission, in which students enter all application and supporting materials in a central database, and can submit that package to any college or university. This benefits students by cutting down on repetitive paperwork, and institutions by allowing receipt of a standardized, digital application.

"The harmonized system must encompass the full scope of reporting indicated by statute and regulation and most, if not all, of the reporting currently requested by organizations," the committee wrote. "A thoughtfully constructed system that meets these needs, allows institutions to filter for information relevant to them, and maintains a nimble updating capacity has the best chance to be broadly accepted by individual and organizational users."

The committee painted with a rather broad brush those who would need to report their financial conflicts of interest. Reporting should be required not only of the physician or researcher, but also of close family members who receive any remuneration that could be construed as a conflict.

Not only would such a system simplify and clarify the disclosure process, it also would fulfill at least some of the requirements of the Physician Payment Sunshine Act, a part of the Affordable Care Act. The Sunshine Act requires manufacturers whose products are covered by federal health care programs including Medicare and Medicaid to report gifts and payments made to teaching hospitals, physicians, and their immediate family members.

That law likely portends a great increase in the complexity of financial disclosure, wrote Dr. Lichter, lead author of the IOM discussion paper.

Before such a system can be designed, however, some groundwork is necessary. Different bodies have different definitions of the same financial reporting requirement. The National Institutes of Health defines it as salary, payment, stocks and options, and ownership. The International Committee of Medical Journal Editors defines it as resources received directly or indirectly that supported work on any given manuscript.

The IOM committees suggested that data be reported separately for each financial relationship, including the beginning and ending dates of the relationship, the name of a drug or device, and the value of each relationship.

Administering the database is an entirely different – and just as complicated – matter, according to the committee. Those who are obliged to report conflicts need to feel confident that their data can’t be compromised, so each person should have full ownership and control of their information.

A centralized system is one option. In this scenario, all data are stored and managed in a single repository from which users could enter and request information. While this would require a large up-front investment, it offers several advantages, the committee said.

• It would be easy to manage and operate.

• It could be easily changed as reporting requirements change.

• When linked to organizational systems, data transfer would be quick and easy.

A second option is a federated system which would link many now-separate databases that would then be available through one portal. Since this approach is based on existing systems, the initial investment would probably be less. However, it would require reconfiguring almost every one of those databases in order to link them.

In either scenario, data should be accessible not only via computer but also via mobile devices.

As with any large project, a harmonized reporting system will create its own personnel requirements, the committee wrote. These could be served by an existing entity, or by something entirely new.

"Creation of a new entity provides the opportunity for de novo formulation of practices and processes; however, the cost may be high. Developing the activity under the roof of an existing organization allows for building on existing infrastructure, thereby decreasing costs up-front. Over time, a freestanding operation could be established if indicated," the committee wrote.

The system would also need the guidance of a secretariat composed of stakeholders. That group would ensure that the database continued to serve members to the fullest.

The committee also addressed funding such centralized system. "The revenue stream ... might flow from several sources: grants from interested organizations and/or philanthropies, membership dues, subscription fees, licensing, or a hybrid of multiple sources."

Subscription fees would likely be tiered, depending on the required level of service. Committee members envisioned this as being similar to the different subscription levels for online income tax programs, with the lowest fee corresponding for the simplest returns.

The current system of repeated and disparate disclosure submissions is destined to become an unwieldy dinosaur, Dr. Lichter wrote in his editorial.

"It would be difficult to imagine a more cumbersome and confusing system, one in which even the most diligent investigator runs the risk of producing an inaccurate report," wrote Dr. Lichter, who is also chief executive officer of the American Society of Clinical Oncology.

Committee meetings will continue, and independent contractors are working on the specific details, according to Dr. Lichter.

"Outside consultants have been engaged to create a full business plan, including the system’s technical specifications, software needs, hosting opportunities, data governance, cost, and opportunities for a revenue stream that would allow the system to self-sustain."

The Institute of Medicine supported the work. Dr. Lichter had no financial disclosures.

A single, harmonized database for disclosing conflicts of interest could save academic centers, researchers, and the entities that fund their work a myriad of headaches.

Rather than completing disparate disclosure forms for every research application or journal submission, users would enter their baseline information into a central system and update it as needed. Every time the information is required, those who request permission could pull a digital copy and format it according to their needs.

A new system could be launched as early as late 2013 or early 2014, said Dr. Allen Lichter, a member of the committee charged with its framing.

"The time has come for such a harmonized, centralized disclosure system to be created for the benefit of everyone who must produce or receive disclosure information," Dr. Lichter wrote in a viewpoint published Nov. 28 in JAMA (2012;308:2093-94). "Such a system can be designed and implemented as one element in a process to help ensure that research can progress in a trusted, transparent fashion, thereby increasing trust among the public and health care professionals in new medical products that are brought to the benefit of patients."

The centralized system was published in a discussion paper from the Institute of Medicine (IOM), which last year convened a stakeholders’ meeting to explore the possibility.

According to the committee’s paper, a centralized system would be similar to the common application for undergraduate college admission, in which students enter all application and supporting materials in a central database, and can submit that package to any college or university. This benefits students by cutting down on repetitive paperwork, and institutions by allowing receipt of a standardized, digital application.

"The harmonized system must encompass the full scope of reporting indicated by statute and regulation and most, if not all, of the reporting currently requested by organizations," the committee wrote. "A thoughtfully constructed system that meets these needs, allows institutions to filter for information relevant to them, and maintains a nimble updating capacity has the best chance to be broadly accepted by individual and organizational users."

The committee painted with a rather broad brush those who would need to report their financial conflicts of interest. Reporting should be required not only of the physician or researcher, but also of close family members who receive any remuneration that could be construed as a conflict.

Not only would such a system simplify and clarify the disclosure process, it also would fulfill at least some of the requirements of the Physician Payment Sunshine Act, a part of the Affordable Care Act. The Sunshine Act requires manufacturers whose products are covered by federal health care programs including Medicare and Medicaid to report gifts and payments made to teaching hospitals, physicians, and their immediate family members.

That law likely portends a great increase in the complexity of financial disclosure, wrote Dr. Lichter, lead author of the IOM discussion paper.

Before such a system can be designed, however, some groundwork is necessary. Different bodies have different definitions of the same financial reporting requirement. The National Institutes of Health defines it as salary, payment, stocks and options, and ownership. The International Committee of Medical Journal Editors defines it as resources received directly or indirectly that supported work on any given manuscript.

The IOM committees suggested that data be reported separately for each financial relationship, including the beginning and ending dates of the relationship, the name of a drug or device, and the value of each relationship.

Administering the database is an entirely different – and just as complicated – matter, according to the committee. Those who are obliged to report conflicts need to feel confident that their data can’t be compromised, so each person should have full ownership and control of their information.

A centralized system is one option. In this scenario, all data are stored and managed in a single repository from which users could enter and request information. While this would require a large up-front investment, it offers several advantages, the committee said.

• It would be easy to manage and operate.

• It could be easily changed as reporting requirements change.

• When linked to organizational systems, data transfer would be quick and easy.

A second option is a federated system which would link many now-separate databases that would then be available through one portal. Since this approach is based on existing systems, the initial investment would probably be less. However, it would require reconfiguring almost every one of those databases in order to link them.

In either scenario, data should be accessible not only via computer but also via mobile devices.

As with any large project, a harmonized reporting system will create its own personnel requirements, the committee wrote. These could be served by an existing entity, or by something entirely new.

"Creation of a new entity provides the opportunity for de novo formulation of practices and processes; however, the cost may be high. Developing the activity under the roof of an existing organization allows for building on existing infrastructure, thereby decreasing costs up-front. Over time, a freestanding operation could be established if indicated," the committee wrote.

The system would also need the guidance of a secretariat composed of stakeholders. That group would ensure that the database continued to serve members to the fullest.

The committee also addressed funding such centralized system. "The revenue stream ... might flow from several sources: grants from interested organizations and/or philanthropies, membership dues, subscription fees, licensing, or a hybrid of multiple sources."

Subscription fees would likely be tiered, depending on the required level of service. Committee members envisioned this as being similar to the different subscription levels for online income tax programs, with the lowest fee corresponding for the simplest returns.

The current system of repeated and disparate disclosure submissions is destined to become an unwieldy dinosaur, Dr. Lichter wrote in his editorial.

"It would be difficult to imagine a more cumbersome and confusing system, one in which even the most diligent investigator runs the risk of producing an inaccurate report," wrote Dr. Lichter, who is also chief executive officer of the American Society of Clinical Oncology.

Committee meetings will continue, and independent contractors are working on the specific details, according to Dr. Lichter.

"Outside consultants have been engaged to create a full business plan, including the system’s technical specifications, software needs, hosting opportunities, data governance, cost, and opportunities for a revenue stream that would allow the system to self-sustain."

The Institute of Medicine supported the work. Dr. Lichter had no financial disclosures.

BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.

After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.

She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.

Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.

At last follow-up, fasting plasma glucose level had normalized, hemoglobin A_1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.

There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.

Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m² to 73 mg/m²; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.

Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.

In this group, there were no significant changes in HbA_1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.

Dr. Occhipinti said she had no relevant financial disclosures.

BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.

After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.

She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.

Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.

At last follow-up, fasting plasma glucose level had normalized, hemoglobin A_1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.

There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.

Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m² to 73 mg/m²; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.

Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.

In this group, there were no significant changes in HbA_1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.

Dr. Occhipinti said she had no relevant financial disclosures.

BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.

After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.

She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.

Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.

At last follow-up, fasting plasma glucose level had normalized, hemoglobin A_1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.

There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.

Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m² to 73 mg/m²; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.

Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.

In this group, there were no significant changes in HbA_1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.

Dr. Occhipinti said she had no relevant financial disclosures.